[Appearance of a chronic myeloid leukemia in Waldenström's macroglobulinemia].

Philadelphia chromosome-positive chronic myeloid leukaemia (CML) developed three years after the diagnosis of Waldenström macroglobulinemia (WM) in a patient who had received chlorambucil and prednisone during this time. Treatment with busulphan was started and two and a half years later the died in blastic crisis. Six months before the blastic transformation of the leukaemia the amount of IgM, which remains stable (above normal values) along the chronic phase, initiates a decrease, reaching normal values in the phase of acute transformation. CML is a very rare second neoplasia in patients receiving anticancer drugs. The correlation between the decrease of IgM and the blastic crisis is very interesting. We do not find an explanation for this finding although similar observations have been described heralding the appearance of second neoplasias in WM, and one might speculate with a possible role of IgM in the control of chronic phase of the myeloid leukaemia or if the overgrowth of blastic cells could overwhelm the development of lymphoplasmacytoid cells.


Diffusion and focus in sexual networking: identifying partners and partners' partners.

This article describes the second stage of a research project on sexual networking that aims to further understanding of the spread of sexually transmitted diseases and HIV/AIDS in Ondo State, Nigeria. A sample of 488 males aged 15-50 were interviewed in depth to ascertain (1) the numbers and characteristics of their sexual partners, (2) the numbers and characteristics of the partners of those partners, and (3) the extent to which these relationships were commercial. In addition, a census was taken of all commercial sex establishments in order to estimate the numbers of their clients. The results show that male (and female) sexual networking is extensive, that in most nonmarital relationships men do not have accurate knowledge of their partners' partners, and that detailed questioning provides a reasonably accurate picture of the number of these relationships that are commercial in nature. The situation revealed was one of sexual diffusion rather than one with a strong focus on commercial sex workers, which fits the model of a slowly increasing HIV/AIDS epidemic rather than an explosive one.


Changing men's attitudes and behavior: the Zimbabwe Male Motivation Project.

A multimedia communication campaign was conducted between 1988 and 1989 to promote family planning among men in Zimbabwe. The campaign consisted of a 52-episode semiweekly radio soap opera, about 60 motivational talks, and two pamphlets about contraceptive methods. Changes over time were measured by comparing a subset of a follow-up survey conducted from October to December 1989 to a baseline survey conducted from April to June 1988. Men exposed to the campaign were also compared to men who were not exposed. The follow-up survey revealed that the campaign reached 52 percent of men aged 18 to 55. Among married Shona-speaking men, use of modern contraceptive methods increased from about 56 percent to 59 percent during the campaign. Condom use increased from about 5 percent to 10 percent. Awareness and current use of modern contraceptives was also higher among men exposed to the campaign, primarily because of their greater awareness of condoms. Men exposed to the campaign were significantly more likely than other men to make the decision to use family planning and to say that both spouses should decide how many children to have.


Evidence from peninsular Malaysia of breastfeeding as a contraceptive method.

This report examines Malaysian women's perceptions of the contraceptive effect of breastfeeding, the determinants of their perceptions, and any effect these perceptions might have on nursing duration and contraceptive use. The report also considers whether women are consciously replacing breastfeeding with modern contraceptive methods. Data from the 1976 Malaysian Family Life Survey are analyzed, and the author concludes that Malaysian women do perceive that breastfeeding has a contraceptive effect, but that this perception is not universal. Ethnicity and desire for a particular family size are the most significant determinants of this perception. Finally, Malaysian women's recognition of the contraceptive effect of nursing does not influence either the duration of their breastfeeding or their adoption of contraception. Malaysian women may not be abandoning breastfeeding to adopt contraception. More probably, breastfeeding declines and contraceptive prevalence increases with modernization.


Contraceptive use in Matlab, Bangladesh in 1990: levels, trends, and explanations.

The results of a 1990 knowledge, attitudes, and practice survey in Matlab, Bangladesh, indicate that contraceptive prevalence has risen to 57 percent in the maternal and child health/family planning project area. Between 1984 and 1990 significant increases were registered in the proportions of women using contraceptives for the purposes of spacing and limiting births. By 1990 fertility control in the intervention area had become so widely diffused that educational differentials in contraceptive practice were no longer evident. Although significant gains in contraceptive use were also evident in the neighboring comparison area during this period, at 27 percent, prevalence there still remained substantially below the levels in the intervention area. The disparity in contraceptive use between the two areas is adequately explained neither by differences in socioeconomic conditions nor in the demand for family planning, but rather by differences in the intensity, coverage, and overall quality of their family planning programs.


An experiment using a month-by-month calendar in a family planning survey in Costa Rica.

Recent demographic surveys have incorporated a month-by-month calendar for the five-year reference period before the survey for the recording of fertility-related events (sexual unions, contraceptive use, pregnancies, and breastfeeding). In the 1986 survey of Maternal and Child Health and Family Planning in Costa Rica, approximately one-half of the 3,527 women interviewed were administered a questionnaire with traditional fertility and family planning questions; the other half were asked virtually the same questions, but the women's responses were entered in a month-by-month calendar. The assignment of questionnaire type was randomly alternated by cluster. Comparisons of the number of events (live births, pregnancy losses, and contraceptive use) showed that more events were recorded among the women in the calendar group. Significantly less erroneous superposition of events (contraceptive use in the last trimester of pregnancy and hormonal contraceptive use in the first month postpartum) was noted when the calendar was used.


How to estimate the total receptor concentration when the specific radioactivity of the ligand is unknown.

A computation method is presented allowing a direct determination of the total receptor concentration from a competitive displacement curve. Compared to the classical method based on the numerical processing of binding data, the proposed method has the advantage of being more accurate and of not requiring knowledge of the specific radioactivity of the ligand.


The role of individual human cytochromes P450 in drug metabolism and clinical response.

Recent advances in the study of human cytochromes P450 by protein purification, molecular cloning techniques and analysis of polymorphisms has led to increased understanding of the role of the various forms in the metabolism of clinically important drugs. In particular, the substrate specificity of one form, CYP2D6, is well established. CYP2D6 shows polymorphism, with 5-10% of Caucasians (poor metabolizers) not expressing this enzyme. The molecular basis of this deficiency is now well understood and methods for the detection of poor metabolizers are discussed, as well as the effect of the polymorphism on drug metabolism. Substrate specificities and possible polymorphisms in other cytochromes P450 are also discussed.


Neuroprotective role of adenosine in cerebral ischaemia.

Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production is enhanced when the energy demand is larger than the rate of energy supply. Adenosine acts on specific receptors that are present in most cells in the body and that produce cellular effects that tend to antagonize a number of pathological events thought to be instrumental for ischaemic nerve cell death. Karl Rudolphi and colleagues review evidence for the neuroprotective potential of adenosine and indicate some targets for drug development.


[The structure and function of the chromosomal nucleolus organizer regions: the molecular, cytological and clinical aspects].

Numerous data concerning nucleolar organizer region (NOR) structure and function in normal and pathological human cells are analysed. The contents of argentophilic nucleolar proteins vary in the cells tested. The silver-stained test is closely connected with cellular proliferative potentials and differentiation status of the cells. This test also depends on the level of tumor cell malignancy and seemed to be very useful for megakaryocyte and cardiomyocyte studies. In summary, the NOR silver-staining approach is of great value for both fundamental cytological investigations and wide medical practice.


[The ultrastructure of the centrosome in cytoplasts and its alteration under the action of ouabain].

It has been shown that after enucleation of the PE cells with cytochalasin D the centrioles remain in approximately 80% of cytoplasts. Some cytoplasts contain only single centriole, either a mother (active) of a daughter (inactive) one. 20% cytoplasts have no centrioles. 2h after enucleation the centrosome structure in the cytoplasts did not differ from that in normal cells. 14-16 h after enucleation in many cytoplasts large secondary lysosomes and lipid droplets appeared around the centrosome. At this time in some cytoplasts in the centrosome we observed free microtubule convergence foci. 14-16 h after the enucleation, some cytoplasts have doubling centrioles. Under the influence of ouabain (30 min), the number of active centrioles oriented perpendicularly to the substrate plane in the cytoplasts increased. We suggest that the preferentially perpendicular orientation of centrioles to the substrate plane does not depend on the nuclear activity.


[The mitogenic effect of insulin isolated from the mammalian brain on Swiss 3T3 cells].

Mitogenic properties of the insulin derived from pig brain were compared with the action of pancreatic (standard) pig insulin and epidermal growth factor (EGF) using the culture of Swiss 3T3 cells. The brain insulin, likely as the pancreatic insulin, induced uptake of 14C-thymidine by resting cells in a dose-dependent manner at concentration of 0.5-2.0 micrograms/ml in culture medium. However, at equal concentrations of these hormones the proliferating effect of the brain insulin appeared to be 2-fold higher than the effect of the pancreatic hormone. At the same time the mitogenic action of both hormones was lower than that of EGF (10 ng/ml). The additive effect of the brain insulin and EGF, administered in combination, was more pronounced than the effect of the pancreatic insulin combined with EGF. The data obtained suggest a possible participation of brain insulin in the process of nerve cell proliferation.


[Growth factor from the tissues of the marine mollusk Mytilus edulis].

The absence of specific stimulators of cell proliferation, i.e. of growth factors, is one of the causes of failure in long-term cultivation of the marine invertebrate cells. In search for such stimulators in tissues of marine invertebrates, we succeeded in discovering in some tissues a stimulator of cell proliferation, similar to EGF, with a comparatively high content of it in tissues of Mytilus edulis. The similarity of the obtained factor with EGF was shown by the substitution of 125I-EGF, connected with EGF receptors on the surface of A431 cells, with analysed extracts, as well as by the ability of this extract to induce the internalization of EGF-receptor complexes. The fraction of acid/ethanol extract of M.edulis stimulating the cell proliferation in resting mouse fibroblasts Swiss 3T3, was obtained in the same conditions as EGF did, using reversed phase chromatography. Thus, the factor from tissues of M.edulis may belong to the family of EGF-like factors.


[Endoplasmic reticulum (a review of the literature)].

Recent data on the structural and molecular organisation of the endoplasmic reticulum (ER) are reviewed. A special attention is paid to the mechanism of soluble and integral membrane protein translocation across the ER bilayer. A model of phospholipid-coupled polypeptide translocation is introduced served to overcome hydrophobic and (or) conformational constraints during the passage of polar amino acid residues within a polar environment of the ER membrane. In addition the mechanisms of diverse covalent and noncovalent post-translocational polypeptide modifications are considered, together with the process of the sorting events among ER-resident polypeptides and those destined to leave the ER domain for the Golgi apparatus.


[The effect of the treatment of skin wounds in rats with hydrolytic enzymes on the synthetic activity of the epidermocytes].

Epidermis cells synthetic activity was studied by a luminescent microscopy method. Different conditions of skin wound healing in intrascapular region were investigated on 84 rats-males. Daily effect of 0.2% trypsin or 0.1% ronidase solution on the healing surface for 20 min has been shown to increase basal layer cells synthetic activity of forming epidermis in comparison with control. However, maximum raise of epidermis cells functional activity after ronidase influence was observed already on the 4th day, while after trypsin action--only on the 7th. Epithelial cells synthetic activity decreases several days before total skin defect epithelialization. In all experiments their activity stabilizes not less than one month after the operation. We have come to a conclusion that the mechanism of healing acceleration due to proteolytic enzymes depends on basal layer cells synthetic activity of forming epithelium.


[The characteristics of the internalization of normal and mutant receptors for the growth factor released by thrombocytes].

The platelet-derived growth factor (PDGF) is a major mitogen in serum for connective tissue derived cells in culture. The influence of receptor structure on the ability of PDGF receptor to be internalized was studied using cell lines transfected with different PDGF-receptor constructions. CHO cell lines expressing either normal PDGF receptor (CHO wt cells) or truncated PDGF receptor, lacking all but 19 amino acids of the intracellular domain (CHO-ECTM cells) were stained according to the method of indirect immunofluorescence with monoclonal antibody B2 to PDGF receptor. It has been found that after a 30-min incubation of the CHO wt cells at 37 degrees C in the presence of PDGF-BB a typical process of endocytosis is observed, while after a 2 h incubation in the same conditions the staining of the cells is absent which suggested the existence of the down-regulation and the process of degradation of PDGF receptor in CHO wt cells. In contrast, in the case of CHO-ECTM cells after both 30-min and 2-h incubation of cells in the presence of PDGF-BB a bright staining of margins and a low staining of the cytoplasm are observed. When the cells where incubated in the presence of lysosomotropic drug chloroquine (0.1 mM), that inhibits degradation of the receptor, the immunostaining of CHO wt cells is changed, with bright compact spots appearing. But in CHO-ECTM cells the fluorescence pattern is not changed. To examine the rate of endocytosis of PDGF-BB, both the types of cells were incubated in the presence of 2 ng/ml of 125I-PDGF-BB.(ABSTRACT TRUNCATED AT 250 WORDS)


[The antioxidant properties of tumor cell subpopulations].

A study was made of the antioxidative activity (AOA), of the activity of glytathionreductase and catalase, and of SH-group concentration in suspensions of intact cells from eight fractions of the rat ascitic ovary tumor. A correlative bond was detected between AOA, the activity of antioxidative enzymes, and SH-group concentration. It was shown that antioxidative properties of the fractions containing resting (G0) and polyploid cells were higher than those of proliferating diploid cells.


[The cultivation of mouse and human lymphoid cells on serum-free media].

The optimum composition of several serum-free media has been established for a long-term cultivation of hybridomas, lymphoid and erythroleukemic cells. The medium DME/F12 appeared to be the medium of choice. It is necessary to supplement the basic medium with lipid and iron transport proteins (bovine serum albumin, transferrin) and peptide hormone (insulin) for obtaining stable results. However, there are differences in successful growth of examined cell lines under serum-free conditions: some of them acquire saturation density comparable with that of the control medium (hybridomas derived from myeloma Sp2/0-Ag14, cell lines K-562, Raji) but other lines do not (hybridoma derived from myeloma NS0/1, cell lines Namalwa, RPMI 1788, Molt-4). Thus, these serum-free media are not universal, therefore each new hybridoma and cell line should be tested to determine the suitability for them of some proposed media. The high effectiveness of cultivation under serum-free conditions can be presumably achieved by optimization of both qualitative and quantitative composition of the serum replacement and of the basic medium.


[The effect of heavy metal salts on the embryonic development of the common frog].

To elaborate methods of biological testing during monitoring of the environment, a study was made of the effect of heavy metal salts on frog embryos and of the influence of temperature on the extent of toxicity of these substances. It was shown that the early stages of embryogenesis were more sensitive to this toxic effect. The differences in the effect of heavy metals are expressed not only in the extent of toxicity, but also in the pattern of change in toxicity as related to concentration. A rise in temperature of the solution containing heavy metals results in a relative increase in the number of abnormal larvae, whereas a decrease in temperature of the solution leads to a higher mortality at the earliest stages of embryogenesis. The latter, apparently, is due to a longer duration of development at low temperature, and thus, to a longer exposure of embryos to toxic effect. This is more pronounced at earlier stages of development, more vulnerable (sensitive) to toxicants. The estimation of toxicity of a substance by the pathological changes induced in embryos and larvae is one of the most sensitive methods, which allows not only to determine the extent of toxicity, but also to give prognosis of its possible effect on the population.


Effect of sterol alterations on conjugation in Saccharomyces cerevisiae.

Sterol auxotrophic strains of Saccharomyces cerevisiae were grown and allowed to conjugate on media supplemented with various sterols. The mating efficiency of the auxotrophs is perturbed by the replacement of the normal yeast sterol, ergosterol, with other sterols. After 4 h of mating, cells grown on ergosterol exhibited a 30-fold higher productive mating efficiency than those cells grown in stigmasterol. Aberrant budding by the conjugants was enhanced following incubation on stigmasterol and other non-ergosterol sterols. Using light and electron microscopy, we demonstrated that there is a reduced ability for stigmasterol-grown cells to undergo cytoplasmic fusion during conjugation. Many of the mated pairs remained adherent but prezygotic even after 12 h of incubation. The addition of ergosterol to cells previously grown on stigmasterol rescued the organisms, allowing for zygote formation and normal budding.


Transport of malic acid in the yeast Schizosaccharomyces pombe: evidence for a proton-dicarboxylate symport.

The transport system for malic acid present in Schizosaccharomyces pombe cells, growing in batch culture on several carbon sources, has been studied. It was found that the dicarboxylic acid carrier of S. pombe is a proton-dicarboxylate symporter that allows uphill transport and accumulation as a function of delta pH with the following kinetic parameters at pH 5.0: Vmax = 0.1 nmol of total malic acid s-1 mg (dry weight) of cells-1 and Km = 1.0 mM total malic acid. Malic acid uptake (pH 5.0) was accompanied by disappearance of extracellular protons, the uptake rates of which followed Michaelis-Menten kinetics as a function of the acid concentration. The Km values calculated as the concentrations either of anions or of undissociated acid, at various extracellular pH values, pointed to the monoanionic form as the transported species. Furthermore, accumulated free acid suffered rapid efflux after the addition of the protonophore carbonyl cyanid m-chlorophenyl hydrazone. These results suggested that the transport system was a dicarboxylate-proton symporter. Growth of cells in a medium with glucose (up to 14%, w/v) and malic acid (1.5%, w/v) also resulted in proton-dicarboxylate activity, suggesting that the system, besides being constitutive, was still active at high glucose concentrations. The following dicarboxylic acids acted as competitive inhibitors of malic acid transport at pH 5.0: D-malic acid, succinic acid, fumaric acid, oxaloacetic acid, alpha-ketoglutaric acid, maleic acid and malonic acid. In addition, all of these dicarboxylic acids induced proton movements that followed Michaelis-Menten kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)


Polyamines and cell wall organization in Saccharomyces cerevisiae.

Cells of Saccharomyces cerevisiae 179-5, an ornithine decarboxylase mutant (spe-1), showed several ultrastructural abnormalities when cultivated in the absence of polyamines. Besides the appearance of microvacuole-like spaces in the cytoplasm and of deformed nuclei, the most important alterations seemed to be located in the cell wall, which was thicker and of heterogeneous texture, and in the cell membrane, of irregular contour. These modifications could not be evoked by general stress conditions elicited by lack of nutrients. The relative levels of cell wall polysaccharides were altered in polyamine-deprived organisms, giving an envelope with increased mannan and decreased glucan content; this cell wall was incompletely attacked by the lytic enzyme zymolyase. Polyamine depletion led also to some abnormalities in the budding pattern. The above observations suggest the involvement of polyamines in the correct structure and organization of the yeast cell.


Fluorocytosine causes uncoupled dissipation of the proton gradient and behaves as an imperfect substrate of the yeast cytosine permease.

At pH 5-6 ATP-depleted washed cell preparations of strain NC233-10b[pII4-9], in which the cytosine permease was overexpressed, absorbed cytosine, hypoxanthine or fluorocytosine stoichiometrically with, respectively, about 1, 1.4 and 5 proton equivalents. The cellular pH fell proportionately. The membrane depolarization caused by each compound was assayed in the presence of glucose with a voltage-sensitive dye and increased in the same order. Fluorocytosine significantly lowered the growth yield that a 'petite' strain of the yeast formed at limiting glucose concentrations. At pH 5.6 with extracellular [K+] below 1 mM, each of the three substrates was accumulated about 200-fold from a dilute solution at the expense of the proton gradient. This concentration ratio corresponds to a solute gradient (delta mu(s)) of 13 kJ mol-1. Raising [K+]o systematically lowered the substrate accumulation ratio and delta muH. The mean ratio delta mu(s)/delta muH was 0.82 for all three substrates. It was concluded that whereas the behaviour of cytosine approximated to that expected for a symport of unit proton stoichiometry, the absorption of protons with fluorocytosine and, to a lesser extent, hypoxanthine, was only partly conserved as useful work. A possible mechanism of this novel phenomenon is outlined.


DNA transformations of Candida tropicalis with replicating and integrative vectors.

The alkane-assimilating yeast Candida tropicalis was used as a host for DNA transformations. A stable ade2 mutant (Ha900) obtained by UV-mutagenesis was used as a recipient for different vectors carrying selectable markers. A first vector, pMK16, that was developed for the transformation of C. albicans and carries an ADE2 gene marker and a Candida autonomously replicating sequence (CARS) element promoting autonomous replication, was compatible for transforming Ha900. Two transformant types were observed: (i) pink transformants which easily lose pMK16 under non-selective growth conditions; (ii) white transformants, in which the same plasmid exhibited a higher mitotic stability. In both cases pMK16 could be rescued from these cells in Escherichia coli. A second vector, pADE2, containing the isolated C. tropicalis ADE2, gene, was used to transform Ha900. This vector integrated in the yeast genome at homologous sites of the ade2 locus. Different integration types were observed at one or both ade2 alleles in single or in tandem repeats.


DIT101 (CSD2, CAL1), a cell cycle-regulated yeast gene required for synthesis of chitin in cell walls and chitosan in spore walls.

A mutant screen has been designed to isolate mutants in Saccharomyces cerevisiae deficient in spore wall dityrosine. As shown by electron microscopy, most of the mutant spores lacked only the outermost, dityrosine-rich layer of the spore wall. Mutant dit101, however, was additionally lacking the chitosan layer of the spore wall. Chemical measurements showed that this mutant does not synthesize chitosan during sporulation. The mutant spores were viable but sensitive to lytic enzymes (glusulase or zymolyase). Unlike most of the dit-mutants, dit101 did show a distinctive phenotype in vegetative cells: they grew normally but contained very little chitin and were therefore resistant to the toxic chitin-binding dye, Calcofluor White. The cells showed barely detectable staining of the walls with Calcofluor White or primulin. The decrease in the amount of chitin in vegetative cells and the absence of chitosan in spores suggested that the mutant dit101 could be defective in a chitin synthase. Indeed, a genomic yeast clone harboring the gene, CSD2, sharing significant sequence similarity with yeast chitin synthases I and II (C. E. Bulawa (1992), Mol. Cell. Biol. 12, 1764-1776), complemented our mutant and was shown to correspond to the chromosomal locus of dit101. Thus, the mutations dit101 and csd2 (and probably also call; M. H. Valdivieso et al., (1991), J. Cell Biol. 114, 101-109) were shown to be allelic. The gene was mapped to chromosome II and was located about 3 kb distal of GAL1. Using this DNA clone, a transcript of about 3500-4000 nucleotides was detected. Comparing RNA isolated from vegetative cells and from sporulating cells at different times throughout the sporulation process, no significant differences in DIT101 transcript levels could be detected indicating absence of sporulation-specific transcriptional regulation. However, the amount of DIT101 transcript changed significantly at different stages of the mitotic cell cycle, peaking after septum formation, but before cytokinesis. As most of the chitin synthesis of vegetative cells occurs at this stage of the cell division cycle, chitin synthesis mediated by DIT101 could be primarily regulated at the level of transcription in vegetatively growing cells.


Genetic and physical mapping of the WBP1 locus close to CENV.

The WBP1 locus, encoding an essential component of the N-oligosaccharyl transferase, was mapped both genetically and physically. The gene is located on chromosome V between CENV and gcn4. The distance from CENV sequences is 2 kb.


The allantoin and uracil permease gene sequences of Saccharomyces cerevisiae are nearly identical.

We have determined the structure of the allantoin permease (DAL4) gene of Saccharomyces cerevisiae. The gene putatively encodes a hydrophobic protein with a M(r) of 71,755. It possesses the alternating hydrophobic-hydrophilic regions similar to those found in many other integral membrane proteins. The most striking feature of the allantoin permease component encoded by DAL4 is its striking similarity to the uracil permease component encoded by FUR4. Although data available indicate that these proteins do not share any overlap of function, their predicted protein sequences are 68% identical, 81% similar, and their DNA sequences are 70% identical. The upstream regulatory region of DAL4 contains all of the characterized cis-acting elements previously reported for inducible allantoin pathway genes: six sequences homologous to UASNTR, the element responsible for nitrogen catabolite repression-sensitive activation of allantoin pathway gene expression, and two sequences homologous to the cis-acting element responsible for inducer-responsiveness of the allantoin pathway genes, UIS. The finding of these homologous sequences predicted to exist on the basis of DAL4's expression characteristics, supports and strengthens the suggestion that these elements mediate the functions we have previously ascribed to them.


A simple method for visualization of phenolics exudation by roots of intact lupin plants; the effect of nitrate and pH.

Phenolics exudation by imbibed seeds and roots of intact lupin plants (Lupinus albus L.) was studied during the first 4 days of growth by a new agar test with specific reagents for phenolics (Gibbs reagent, Naturstoffreagenz A). Comparative studies of the phenolics exudation reveal that legumes exude different phenolics (even if not qualitatively, then at least quantitatively) than oat. The exudation of phenolics starts very quickly after the imbibition of seeds and can be visualized as early as 24 h after sowing. In older seedlings, the exudation of phenolics can be detected along root zones and is influenced by nitrate and pH. At acidic pH, nitrate reduces phenolics exudation, but at pH 7.5 the exudation of phenolics becomes restricted to only some root zones. Nitrate must be present in the rooting media for at least 24 h to cause visible changes in the pattern of exudation at different pH values.


The effect of an experimental neoplastic disease on the flux of sodium and potassium ions across red blood cells and on the lipid composition of their membranes.

The erythrocytes from Morris Hepatoma 5123 bearing rats took up Na+ and K+ ions from the incubation medium and released Na+ into the extracellular space at lower rates than did erythrocytes from intact control rats. The lipid composition of erythrocytes membranes from the tumor-bearing rats differed from that of membranes from unaffected rats, showing increased contents of phospholipid phosphorus and a decreased content of cholesterol, resulting in decreased cholesterol:phospholipid molar ratios.


Effect of mesitylene on ethanol metabolism in rat liver microsomes.

Increased catalase activity was observed in the liver microsomal fraction of ethanol-treated rats (10% v/v aqueous ethanol solution per os for 5 weeks). In contrast, cytochrome P-450 concentration and specific activity of NADPH-cytochrome c reductase remained at the same level as in the liver of control rats (drinking water). The ratio of microsomal H2O2-generation to catalase activity was lower in the "ethanol" group than in the control one. This phenomenon seems to be related to the increased contribution of the "peroxidatic" reaction (increased rate of ethanol oxidation). Administration of mesitylene (1,3,5-trimethylbenzene) by gastric tube for 3 days (5 mmoles per kg daily) increased cytochrome P-450 concentration, specific activity of NADPH-cytochrome c reductase and ethanol metabolism.


On the possibility of involvement of glutamate:glyoxylate and serine:glyoxylate aminotransferases from rye (Secale cereale L.) seedlings in the metabolism of tetrapyrrole compounds.

The activity of highly purified L-serine:glyoxylate aminotransferase (SGAT, EC 2.6.1.45) from rye seedlings was inhibited competitively by 5-aminolevulinate (ALA, Ki = 5 mM) SGAT was activated by hematin. Protoporphyrin IX and hematin inhibited irreversibly the activity of highly purified glutamate:glyoxylate aminotransferase (GGAT, EC 2.6.1.2) from rye seedlings. SGAT was found to catalyse transamination between ALA and hydroxypyruvate, whereas GGAT that between ALA and 2-oxoglutarate or pyruvate. It is suggested that SGAT is involved in the process of degradation of the excess ALA which has not been incorporated into porphyrin compounds.


Prediction of protein secondary structure by neural networks: encoding short and long range patterns of amino acid packing.

A complex, cascaded neural network designed to predict the secondary structure of globular proteins has been developed. Information about the local buried-unburied pattern and the average tendency of the particular types of amino acids to be buried inside the globule were used. Nonspecific information about long distance contact maps was also employed. These modifications result in a noticeable improvement (3-9%) of prediction accuracy. The best result for the average success ratio for the testing set of nonhomologous proteins was 68.3% (with corresponding Matthews' coefficients, C alpha,beta,coil equal to 0.60, 0.47, 0.43, respectively).


Luteal phase defects in assisted reproduction: the role of luteal phase supplementation.

Data from literature show that whereas in non-GnRH-a controlled ovarian hyperstimulation cycles luteal phase supplementation is not crucial, its use in GnRH-a/gonadotropins protocols seems to lead to a definite reduction of the negative effects of such drugs. The most important side effect of the hCG use as luteal support is the increased rate of the ovarian hyperstimulation syndrome (OHSS). Therefore its use should be reserved for very selected patients, for those subjects with preovulatory levels of E2 < 2500 pg/ml. As regard the use of progesterone, most authors agree that it has less efficacy than hCG but this depends on the administration route.


Negative effect of stress of in vitro fertilization program on quality of semen.

There are controversial data on the effects of stress on semen quality during treatment for infertility. We have compared the parameters of semen obtained from 84 patients on the day of the ovocyte pick-up during an in vitro fertilization and embryo transfer program (IVF) with those of semen collected from the same patients on the day of admission to the program (up to 3 months earlier). Abnormal semen has been found in 2 of the 84 patients on the day of admission and in 11 on the day of IVF. There were no improvements in semen quality of any patient at the second test. All except two parameters evaluated objectively by the Hamilton-Thorn Motility analyzer were significantly worse (p < 0.001) on the day of IVF, the exceptions were the percentage with moderate or slow motility and the Linear Index. These data indicate that the emotional stress to a subject enrolled in an IVF program negatively affects the quality of semen. Some suggestions are made for improved management of these patients.


Conservative treatment of ectopic pregnancy with intramuscular administration of methotrexate (MTX/CV).

20 cases of unruptured ectopic pregnancies were studied from August 1990 till May 1991. They were treated according to the Sauers et al. (1987) protocol with Methotrexate and rescuvolin. The treatment was successful in all but one case. Six out of 17 cases had a normal pregnancy in the 12 months following treatment. Seventeen out of 20 cases had tubal patency checked with HSG and laparoscopy. We conclude that conservative management of unruptured pregnancy with MTX must be the treatment of choice.


Presurgical treatment of uterine fibroids by using gonadotropin-releasing hormone agonists.

Evaluation of clinical intra- and post-operative benefits of pre-myomectomy therapy with a Gonadotropin-Releasing Hormone Agonist (GnRH-A) (Goserelin) in anemic and non-anemic patients suffering from uterine leiomyomas. Evaluation of ultrasound, estradiol (E2) and hematological measurements before and during treatment with a GnRH-a in thirty women with uterine leiomyomas, comparing pre-treated patients operative time, total intraoperative blood loss, blood counts and febrile morbidity with of thirty-five control women. GnRH-A pre-treatment cures, iron-deficiency anemia, significantly reduces myoma and uterine volume (p < 0.01), total intra-operative blood loss (p < 0.001), decreases post-operative febrile morbidity, though it does not reduce operative time. GnRH-A pre-treatment over a period no longer than two months should be suggested in anemic patients suffering from uterine leiomyomas who have to undergo myomectomy.


[The polymerase chain reaction (PCR) and its application in transfusion medicine and hematology].

The new technique, polymerase chain reaction, used for in vitro DNA fragments amplification is described. The conditions of the reaction and methods of data analysis are discussed as well as the usefulness of this technique in research and medical practice.


Flutamide: a rational approach to hirsutism.

The Authors would show the effectiveness of flutamide, a potent selective antiandrogen, by an analysis of 30 patients with moderate to severe hirsutism. This therapy caused a marked improvement of clinic symptoms.


Successful pregnancy in a pure gonadal dysgenesis with karyotype 46,XY patient (Swyer's syndrome) following oocyte donation and hormonal treatment.

A pregnancy obtained in a patient with 46XY gonadal dysgenesis (Swyer's syndrome) after ovum donation and IVF/ET is described. The efficacy of this technique in overcoming particular cases of otherwise irreversible infertility is discussed.


[Advances in treatment of multiple myeloma].

Median survival time in multiple myeloma treated with melphalan and prednisone does not differ significantly from survivals yielded by combination of alkylating cytostatics. Intensive chemotherapy linked with marrow transplantation provides elongated complete remission more frequently in patients, who reached early remission by conventional means. Multidrug resistance of myeloma plasmocytes has been overcome by adding of verapamil to the VAD program. In recently diagnosed myelomas, it is more rational to assay the survival prognosis and access to intensive therapy.


Sodium and potassium in normal and pathological seminal plasma.

A total number of 273 seminal plasma samples from normozoospermia (n = 91), oligozoospermia (n = 50), oligo-asthenozoospermia (n = 76), asthenozoospermia (n = 10) and azoospermia (n = 46) were analysed for sodium and potassium. A decreased sodium level was seen in pathological groups. A negative correlation was found to be in existence between sodium and potassium in seminal plasma in the groups studied except in azoospermia. Positive correlation was found between sodium and motile spermatozoa in normal and oligozoospermia. In oligo-asthenozoospermia it was negative. Potassium, was negatively correlated with percentage of motile spermatozoa in the groups studied.


[Evaluation of microtest in dextran gel for blood group serology].

Microtest in gel was compared to the traditional, immunohaematological methods. Blood samples of 1.032 persons were tested. From the results presented in this paper we conclude that Gel-test is specific, clear, easy to perform and more sensitive than the traditional methods. It can be used for red cell phenotyping and antibody detection as well. By this technique it was possible to establish the specificity of antibodies of Rh system not found by any other method. The advantage of this test is that nearly all unspecific reactions could be eliminated. The disadvantage concerned the high sensitivity in the detection of cold, clinically insignificant allo- and autoantibodies. Therefore, some modifications for the elimination of these unfavourable reactions were introduced.


[Activity of NK in elderly people].

Optimally healthy elderly persons, selected according to Senior Protocol criteria, aged 60-93 years were characterized by as high level of NK activity as their young adult, 20-35 years old, counterparts. NK activity of the nearly optimally healthy elderly persons of the corresponding age was significantly lower than that of optimally healthy ones. The lowest values of NK activity were noted for the elderly persons suffering from recurring infections of the respiratory tract.


[Evaluation of phagocytic activity of peripheral blood neutrophils in patients after kidney transplantation treated with cyclosporin and prednisone or with azathioprine with prednisone].

In 32 renal transplant patients neutrophil phagocytic activity was evaluated using living bacterial cells of Staphylococcus aureus Oxford 209 P strain. The total group of patients was divided into two subgroups according to the kind of the applied immunosuppressive treatment 1) cyclosporin--12 patients treated with cyclosporin A along with prednisone and 2) azathioprine--20 patients treated with azathioprine along with prednisone. The index of phagocytizing cells i.e. the percentage of neutrophils phagocytizing the bacterial cells was assessed in the investigation of phagocytosis. In the renal transplant patients as compared with the control group, statistically significant increase in the phagocytic of peripheral blood neutrophils in relation to the used bacterial cells of Staphylococcus aureus Oxford 209 P strain was found. Statistically significant differences in the investigated range were also present between the compared subgroups. In the cyclosporin subgroup statistically significant increase was revealed in the percentage of phagocytizing neutrophils.


[Clonal proliferation of less mature granulocytic precursors (CFU-dG) under the influence of neoplastic B lymphocytes in low grade non-hodgkin's lymphomas].

The effect of peripheral blood lymphoma B cells from low grade malignancy non-Hodgkin's lymphoma patients (Kiel classification: lymphocytic, centrocytic, centroblastic-centrocytic lymphomas) on clonal growth of normal marrow granulocytic precursors (CFU-dG) was studied. Using in vivo diffusion chamber culture method it was shown that all the tested lymphoma cells enhanced the CFU-dG growth by releasing humoral factor(s). The effect of stimulation was cell-concentration and cell-source dependent. The colony stimulating activity produced by centrocytic lymphoma cells had higher potency than that released by centroblastic-centrocytic lymphoma cells, whereas lymphocytic lymphoma cells showed the lowest ability to generate the CFU-dG growth-promoting activity (p < 0.01). It was shown that the CFU-dG growth enhancing effect was independent of marrow-derived macrophages and T lymphocytes (p > 0.05). Normal peripheral blood B lymphocytes used as a control did not show any substantial effect on the granulocytic precursors proliferation.


[Effect of thrombin stimulated blood platelets on plasma fibrinolytic activity].

The influence of thrombin stimulated-blood platelets on plasma fibrinolytic activity was evaluated. Thrombin-activated blood platelets have been shown to significantly inhibit plasma fibrinolytic activity before and after venous stasis. This was expressed by a reduction of the digestion area of fibrin dish from 10.3 +/- 3.3 cm2 to 3.7 +/- 1.5 cm2 and from 15.6 +/- 6.8 cm2 to 3.7 +/- 1.7 cm2, respectively.


[Acute nonlymphoblastic leukemia as a secondary malignancy--demonstration of 15 patients].

Among 90,128 patients with malignancies in the years 1976-1989 acute non lymphoblastic leukaemia (ANLL) was diagnosed in 351 patients (0.4%) and in 15 (4.3%) of them ANLL was secondary neoplasm. Secondary ANLL occurred in 10% of all the 148 secondary malignancies observed at that period of time and constituted 6.7% of secondary malignancy in patients with solid tumours and 43% in patients with myeloproliferative syndromes as a first malignant neoplasm. In the treatment of first malignancy radiotherapy was applied in 11 persons, in combination with chemotherapy in 7 of them and chemotherapy alone was given to 4 patients. The appearance of the secondary ANLL was usually preceded by the myelodysplastic syndrome. Morphologically, secondary ANLL belonged mostly to M6 and M4 (8 patients) according to FAB classification. The course of ANLL was fulminant and the disease was completely resistant to the treatment.


[Comparative evaluation of treatment results in advanced multiple myeloma with the help of polychemotherapy with vincristine, doxorubicin, dexamethasone (VAD) or only with dexamethasone].

A prospective clinical trial was undertaken to determine the therapeutical effectiveness of multidrug chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) or only high dose of dexamethasone (D) in 56 patients with multiple myeloma (MM). The group of patients included 41 with intermediate (II) and 15 with high (III) tumor mass. The final evaluation was performed in 19 patients treated with D and in 19 receiving VAD regimen. Improvement was defined by at least 50% reduction of serum myeloma protein concentration or disappearance of light chain proteinuria. The VAD regimen was more effective giving improvement in 90% of patients with no prior therapy and in 44% of patients with reflectory myeloma. In this respect, cytoreduction of the same magnitude was noted both in stages II and III. Higher therapeutical effect of VAD regimen was observed independently of the immunological type of MM. The treatment with D has given the improvement in 56% of patients with no previous therapy. Our results support the usefulness of VAD regimen in MM-patients with no prior therapy and with refractory myeloma. High frequency of therapy-related complications, however, indicates that VAD treatment should rather be reserved for the patients with resistant MM.


Leprosy in HIV-positive and syphilitic young Paraguayan man.

In a borderline lepromatous patient a positive serology for syphilis and HIV 1 has been detected. The patient also had an urinary tract infection with Acinetobacter calcoaceticus. In Paraguay up till now no leprosy cases infected with HIV have been reported.


[Cutaneous neoplasms during leprosy: 2 case reports].

The authors report on two cases of dermal neoplasia in foot trophic disorders observed in leprous subjects. The report includes the description of the clinic and histologic data as well as the surgical technique used; finally, it underlines the importance of a precocious diagnostic so as to obtain a good therapeutic result.


[Leprosy serology: current status and perspectives].

The different serological tests used for leprosy are firstly the methods for the detection of antibodies (anti-PGL1, 35kD, 36kD, LAM), and secondly, the tests to detect the PGL1 antigen from the serum or urine. The antibody detection tests have a good but insufficient specificity for the diagnosis of leprosy patients and their sensitivity is generally high for the multibacillary patients but low for the paucibacillary patients. Their positive predictive value for the diagnosis of patients in a population are very low: 2.1% for the anti-PGL1 ELISA when the prevalence is 1/1000. For the early diagnosis of patients and the follow up of high risk populations, these tests are not cost effective: the number of patients detected in these populations is 10 fold lower than in the general population and the relative risks for developing the disease are not different among seropositive and among seronegative groups. In treated multibacillary patients, the IgM anti-PGL1 level decreases in correlation with the decrease of the bacillary index. For the diagnosis of M. leprae infection in a population, there was no correlation between the anti-PGL1 seroprevalence and the prevalence of the disease. Concerning the PGL1 antigen detection tests, they are specific and sensitive for the diagnosis of multibacillary patients but they cannot be used in routine for technical reasons. In conclusion and to date, the usefulness of serological tests in a leprosy control programme is quite questionable.


[Leprosy survey conducted in the Central African Republic from 1982 to 1985 among the Ba-Benzele Pygmies].

A leprosy survey was conducted from 1982 to 1985 among 2650 semi-sedentarized Pygmies in two camp-villages in the Central African Republic. Leprosy is endemic there, with an estimated prevalence rate of 1.05% and an annual detection rate of 0.2%. In view of its close relations with other neighbouring ethnic groups this Pygmy community can be considered as a target population the study of which provides indications on the transmission and typical course of leprosy in the region and also as a potential focus of contamination. However, the concurrent presence of endemic tuberculosis made it necessary during the survey to look for clinical associations of leprosy and tuberculosis in patients so that the standard multidrug treatment schedules comprising rifampicin could be adjusted accordingly.


Histological changes with combined chemotherapy and immunotherapy in highly bacillated lepromatous leprosy.

Highly bacillated untreated lepromatous cases with an initial BI 4+ of to 6+ were treated with combined multidrug treatment (MDT) and immunotherapy with heat killed Mycobacterium w or BCG. The vaccines were administered intradermally every six months. It was observed that majority of cases on immunotherapy showed increased lymphocytic infiltration (both at local and distant sites) and some cases showed epithelioid cells as well. The lymphocytic infiltration was (slightly) more vigorous in those vaccinated with Mycobacterium w. Such changes were not seen in the patients on MDT alone. Also, the granuloma fraction reduced much faster in cases who were on additional immunotherapy as compared to those on MDT alone. These changes along with evidence of clinical and bacteriological improvements suggest that immunotherapy may have an important supportive role specially in the therapy of anergic lepromatous cases.


Treated-cured indeterminate leprosy: a search for predictive histopathological and immunohistochemical parameters in skin biopsies taken from patients at admission and at clinical discharge.

In a previous study an index (sigma 3) resulting from the summation of three parameters, i.e., presence of bacilli, even in small numbers, in various dermal structures, multiple positive antigen sites as detected by anti-BCG antiserum and dermal nerve involvement, identified 72.22% of cases of indeterminate leprosy which progressed to multibacillary leprosy. The present study was undertaken to investigate possible parameters which might be indicative of indeterminate leprosy which would persist unchanged or be cured (treated cured patients). Thirty treated cured indeterminate leprosy patients were selected from the files of the São Paulo Health Institute and studied by histopathological, immunohistochemical and statistical methods similar to those employed in the previous study. The sigma 3 index was 4.10 +/- 0.60, a finding that places this group of patients in a position close to that of patients changing to paucibacillary leprosy but statistically different from that of patients progressing to multibacillary leprosy. Moreover, it was found that patients belonging to this group have heterogeneous single parameters, some of them suggestive of multibacillary and others of paucibacillary leprosy. Immunologically based techniques mainly employing rabbit anti-BCG serum as the primary antibody have proved to be valuable to detect antigen sites in biopsies from indeterminate leprosy patients and should be used together with the bacillary index during the follow up and clinical discharge control of such patients. In the present study, we show that clinical discharge of these patients did not mean a complete clearance of bacillary antigens.


[Effects of tetraethylammonium chloride and verapamil on the effective refractory period of ischemic myocardium in rabbits].

The effects of potassium ion channel blocker TEA and calcium ion channel blocker verapamil on effective refractory period (ERP) of ischemic ventricular muscle were studied in rabbits. The results showed that ERP of the ventricular muscle in central ischemic zone (CIZ) and border ischemic zone (BIZ) were shortened, respectively, at 10 min and 30 min after coronary occlusion (P < 0.01). The changes of ERP in TEA-treated and verapamil-treated rabbits after coronary occlusion were found to be significantly less than those in untreated rabbits. The results suggest that TEA and verapamil alleviated the degree of ERP shortening after coronary occlusion and may exhibit protective effects on the ischemic myocardium.


[Protective effects of praeruptorin C and nifedipine on ischemia-reperfused injury in working rat hearts].

The effects of praeruptorin C (Pra-C, 15 mg/kg, bid x 3 d, ip) on global myocardial ischemia and reperfusion were investigated in the isolated working rat hearts. The results at 35 min after reperfusion showed that as compared with the values before ischemia, AP, LVSP, +dP/dtmax, -dP/dtmax, LVEDP and T were recovered up to 80 +/- 19%, 82 +/- 16%, 78 +/- 21%, 85 +/- 11%, 136 +/- 77% and 133 +/- 21%, respectively. The corresponding parameters of Nifedipine (Nif, 60 micrograms/kg, bid x 3 d, ip) were 80 +/- 16%, 97 +/- 30%, 102 +/- 24%, 106 +/- 32%, 129 +/- 41% and 145 +/- 46%, respectively. The CF, SV and HR were recovered by 81 +/- 11%, 104 +/- 20% and 78 +/- 7% when using Pra-C and 86 +/- 11%, 106 +/- 25% and 82 +/- 11%, respectively, when using Nif. Additionally, in comparison of Pra-C and Nif with the ischemia group, the levels of creatine kinase released from cardiac cells decreased by 30% and 40%; while calcium accumulation in myocardial mitochondria were 41% and 46%, respectively. The study suggests that the protective effects of Pra-C on myocardial cells in the isolated working rat heart during myocardial ischemia are similar to those Nif.


[Synthesis and bacteriostatic activity of new thiosemicarbazone derivatives--amino mercaptotriazole Schiff bases].

4-amino-3-(furan-2)-5-mercapto-1,2,4-triazole (Ia) and its ten Schiff bases derived from Ia with different aldehydes were synthesized. All the compounds were screened for activity against seven bacteria and three fungi. Most compounds were found to possess different inhibition effect on some bacteria and fungi. The azomethine group of Schiff bases is the active functional group and the substituted groups on the phenyl ring had definite effect on the bacteriostatic and fungistatic activities. 4-(5-Nitrofurfurylideneamino)-3-(furan-2)-5-mercapto-1,2,4-tria zol e (Ik) showed the most powerful antibacterial activity and broad antibacterial spectrum, while 4-salicylideneamino-3-(furan-2)-5-mercapto-1,2,4-triazole possessed strong activity against fungi.


[Studies on anthraquinones from the roots of rubia cordifolia l].

Seven anthraquinones were isolated from the ethyl alcohol extracts of the roots of Rubia Cordifolia L. By means of spectrometric data combined with physico-chemical properties, six of them were identified as 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (I), 1-hydroxy-9,10-anthraquinone(II), 1,2,4-trihydroxy-9,10-anthrequinone(III), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-beta-D-glucoside(IV), 1,2-dijhydroxy-9,10-anthraquinone-2-O-beta-D-xylosyl(1-->6)-beta-D -glucoside(V) and 1,3-dihydroxy-2-hydroxymethyl1-9,10-anthraquinone-3-O-beta-D- xylosyl(1-->6)-beta-D-glucoside(VI). VII is a new compound. Its structure was elucidated to be 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-beta-D-xylosyl(1-->2)-b eta-D- (6'-O-acetyl)glucoside.


[Studies on the chemical constituents of Glycyrrhiza pallidiflora Maxim].

A species of the genus Glycyrrhiza, G. pallidiflora Maxim, growing in Jiangsu and Hebei Provices of China, has been little studied before on its chemical constituents. This paper reports the isolation and chemical elucidation of five compounds from this plant, one of them is a new compound named glypallichalcone (P-2). Their chemical structures were elucidated by means of chemical and spectrometric analysis (UV, IR, MS, 1HNMR and 13CNMR) and were first reported to be present in this plant. Glypallichalcone (P-2), was found to be 4-hydroxy-2,4'-dimethoxy-chalcone. The known compounds were identified to be 4'-O-methylcoumestrol (P-1), N-acetyl-glutamic acid (P-3), formononetin and beta-sitosterol (P-5).


[New monoterpenoids from Cynanchum hancockianum].

Five monoterpenoids have been isolated from the roots of Cynanchum hancockianum (Maxim) AI. Iljinski. Their structures were determined on the basis of spectral evidence. The three new compounds are: 4-p-menthane-1,7,8-triol (III), neohancoside A (IV), neohancoside B (V), and the two knowns: 4-p-menthene-1-8, 9-diol (I), and 4-p-menthane-1,8, 9-triol (II). Compound V was purified by acetylation.


[Trimethylsilylation of testosterone, epi-testosterone and determination of their ratio in urine by GC-MS].

The trimethylsilylation of testosterone and epitestosterone was discussed in detail in this report. Both derivative conditions under which testosterone and epi-testosterone were prepared into TMS-derivatives in the presence of mercaptoethanol as an antioxidizing agent and method for the analysis of the ratio of testosterone to epi-testosterone in urine, based on GC-MS, had been established. The conditions of detection were: carrier gas was helium, derivatives were separated with SE-54 fused silica capillary column, using temperature program and detected by using multiple ion detection mode in which the ion of m/z 432 was the monitoring ion. The method is rapid, sensitive and specific. For the ratio of testosterone to epi-testosterone (testosterone: 20 ng/microliters), there is a linearity between ratio 1:1 and 10:1 (r = 0.998), the limit of detection for testosterone and epi-testosterone is 1 ng, and the minimum concentration of detection in urine is 8 ng/ml.


[Studies on the determination of plasma level and pharmacokinetic parameters of anisodamine by micellar liquid chromatography].

Anisodamine is a tropane alkaloid isolated from the plant Anisodus tanguticus (Maxim) Pasch. It is an anticholine drug widely used in clinics. Micellar liquid chromatography is a new type of HPLC developed in the 1980's. Direct plasma injection technique is the application of micellar HPLC in bioanalyses. In this paper, a micellar HPLC method, which employs n-propanol as modifier, SDS as surfactant, atropine sulphate as internal standard, has been developed. By direct injection, this method was successfully applied to the measurement of plasma level of anisodamine. Application of this method to the study of anisodamine pharmacokinetics was investigated in human volunteers following a single intramuscular injection. The separation was performed in a Shim-pack CLC-CN column (150 mm x 6 mm ID, 5 microns) with a mobile phase of n-propanol-water (15:85) with 45 mmol/L SDS and total ion strength 70 mmol/L by adding phosphate, and detected at 205 nm. The standard curve was linear over the concentration range of 15-750 ng plasma level (r = 0.9972). The measurable lowest concentration was 10 ng/ml plasma (S/N = 3:1). The study of anisodamine pharmacokinetic in man was also described.


[Optimization of the solvent system used for thin layer chromatography. VI. Furthering of the uniform design method].

In this paper, we optimized the solvent systems of sulfa drugs and five traditional Chinese medicines for thin layer chromatography by means of uniform design method. The optimal system for the eleven sulfa drugs is benzene-n-butanol-n-hexane (5.71:2.86:1.43). The optimal systems for Mu Xiang and Jiu Li Xiang are all absolute chloroform. The optimal systems for Liang Mian Zhen and San Cha Ku are all acetonitrile-ethyl ether-methyl chloride-cyclohexane (0.05:0.3:0.1:0.55). The optimal system for Jin Yin Hua is ethyl acetate-methyl chloride-formic acid (1:1:1). The method has been born out to be theoretical, simple and practical. In our opinion, it is an effective systematic method.


[Studies on the analysis of stereoisomer of agarofurans by GC and GC-MS].

The method for separation and identification of three pairs of agarofuran epimers (alpha-and beta-dihydroagarofuran, alpha- and beta-baimuxinol, alpha- and beta-baimuxinol methyl ether) by HRGC and HRGC/MSD is described. The proportion of each pair of isomers was determined and the analytical procedure for isomers of sesquiterpenes was established. Thus, the correct synthetic route can be effectively guided and the study of agarofuran synthesis can be greatly accelerated. The method provides a reliable basis for identifying the products. MS data given in Table 2 may be useful for the identification of agarofuran derivatives.


[Adsorption in stratum corneum and percutaneous penetration of propranolol hydrochloride].

The sorption and rate of permeation of propranolol hydrochloride were measured as a function of drug concentration in the solution bathing rat skin in vitro. The sorption isotherm was nonlinear, and can be expressed in Langmuir form. The lag time and apparent permeability coefficient through intact skin decreased as the concentration of donor compartment increased, and those through stripped skin were not varied. These results indicate that an adsorption process existed when propranolol hydrochloride penetrated through the stratum corneum. Based on the adsorption--diffusion theory, a mathematical formula was developed for expressing the relationship between the concentration of drug and permeability coefficient through the skin quantitatively.


[Hypotensive effects of safflower yellow in spontaneously hypertensive rats and influence on plasma renin activity and angiotensin II level].

Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1-2 g.kg-1.d-1 lowered the blood pressure of spontaneously hypertensive rats (SHR), for about 1.86-3.86 kPa. Five weeks after administration of SY, the plasma renin activity and angiotensin II level diminished in the SHR experimental groups. These suggest that the decrease of blood pressure is mediated by the renin-angiotensin system.


[A new alkaloid from Menispermum dauricum DC--N-desmethyldauricine].

A new phenolic dauricine-type alkaloid together with the know dauricine were isolated from the rhizoma of Menispermum dauricum DC cultivated in Xianning district, Hubei province. Dauricine was obtained as the major alkaloid and was confirmed by comparison with authentic sample. The new alkaloid is an unstable white powder: Based on spectrometric analysis (UV, IR, FAB-MS and 1HNMR) and N-methylation which offered dauricine dimethiodide (V), the structure was elucidated as RR, N-desmethyldauricine (II), which was isolated for the first time from nature.


[Studies on the chemical components of Viscum coloratum. VIII. Isolation and structure of 3-beta-D-glucopyranosyloxy-butanol-2].

From the ethanol extract of Viscum coloratum (Kom.) Nakai, a glucoside of aliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis, the structures have been elucidated as 2-beta-D-glucosyl-3-methylpropanol (VIII), syringin (IX), eleatheroside E (X) and syringenin-4'-O-D-apiosylglucoside (XI). VIII is a new glucoside of aliphatic diol and named 3-beta-D-glucopyranosyloxy-butanol-2. Three other compounds (IX-XI) were found for the first time in this plant.


[Separation and identification of impurities in mifepristone].

In this paper we presented details of methods for the TLC and HPLC separation of mifepristone and its impurities. The results showed that Chinese mifepristone contained five impurities. The major one was isolated by sillca gel column chromatography and thin layer chromatography. On basis of its UV, IR, EIMS and 1HNMR spectral analysis and by comparison with reference substance, it was identified as (11 beta, 17 beta)-11-[(4-methylamino)phenyl]-17-hydroxy-17-(1-propyny)-estra-4 ,9-dien-3 - one. Meanwhile, TLC analysis indicated that French mifepristone contained the same impurity.


[Effect of panaxatriol saponins isolated from Panax notoginseng (PTS) on myocardial ischemic arrhythmia in mice and rats].

PTS, one of the major effective components of Panax notoginseng was found to exert remarked antiarrhythmic activities on coronary artery ligation induced ischemic and reperfused arrhythmias in rats. PTS also reduced the size of myocardial infarct. For i.v. CaCl2-Ach induced atrial fibrillation and/or flutter in mice, PTS produced a significant protective effect. In addition, PTS showed an action of prolonging the life under the condition of normobaric hypoxia.


[Effect of ageing on hepatic biotransformation function and microsomal membrane fluidity in rats].

Microsomes were isolated from livers of male Sprague-Dawley rats at 3-4, 14 and 24 months of age for each group for the determination of monooxygenase components and drug metabolism activities. Some GSH-related enzyme activities in microsomes and cytosol were also measured. DPH (1,6-diphenyl-1,3,5-hexatriene) was used to determine the microsomal membrane lipid region fluidity. Microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activities remained unchanged in old rats, but there were significantly decreases in cytochrome P-450 dependent aminopyrine N-demethylase and aniline hydroxylase activities. Glutathione S-transferase (GST) in cytosol and microsomes and glutathione peroxidase (GSH-Px) in cytosol were also decreased in old rats. Simultaneously, microsomal membrane fluidity of 24-month old rats decreased (measured at 25 degrees C and 37 degrees C), accompanied by an elevation of cholesterol/phospholipid ratio. Results suggest that there might be some relationship between the lipid environment and membrane fluidity changes and the decreases of hepatic biotransformation function.


[Effects of platelet activating factor on the cerebrovascular permeability in rats and the protection by drug].

The action of platelet activating factor in the rat brain was detected by Evans blue staining after injection of PAF into the rat brain. The results show that PAF increased the Evans blue staining of the brain, but no staining was observed without prior injection of PAF. Meanwhile, PAF was shown to stimulate the release of 14C-arachidonic acid (14C-AA) in the cerebral microvascular smooth muscle cells (CMSMC). SZ-1, a new synthetic drug, dose-dependently inhibited the Evans blue staining of the rat brain and the PAF induced 14C-AA release in CMSMC. These results indicate that the action of PAF in the rat brain might be related to the stimulation of AA release. SZ-1 may antagonize the PAF receptor and protect the brain from PAF induced damage.


[Synthesis and antitumor activity of 4-alkylthio-4-deoxy-4'-demethylepipodophyllotxin derivatives].

As a continuing part of our study on the chemistry and antitumor activity of podophyllotoxin, 11 new C-4 S-substituted podophyllotoxin derivatives were synthesised and screened in vitro against L1210 leukemia and KB cells. Thus, 4'-demethylepipodophyllotoxin was reacted with thiols in the presence of BF3. Et2O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-deoxy-4'-demethylepipodophyllotoxin, when reacted with thiols, also gave rise to corresponding thioether (4-alkylthio-4-deoxy-4'-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activity as etoposide in the inhibition against L1210 leukemia, and compounds 9, 10, 12 and 15 also have comparable activity with etoposide against KB cells.


[Synthesis and radiosensitizing activity of benzimidazoles].

In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl-oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3'-pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively.


[Studies on the alkaloid constituents of Jiangyou fu-zi Aconitum carmichaeli from Sichuan].

Six compounds were isolated from the aqueous extract of Aconitum carmichaeli Debx (cultivated in Jiang-you region of Sichuan province). Five of them have been identified as uracil (I), songorine HCl(II), karakoline(III), neoline(IV), and fuzitine(VI). Compound V is a new C19-diterpenoid alkaloid determined as C33H47NO9 and named neojiangyouaconitine.


[Studies on chemical constituents of the gall of Python molurus bivittatus Schlegel].

Two constituents were isolated from the gall of Python molurus bivittus Schlegel, one is sodium taurodeoxycholate (I). The other is a new compound--sodium tauropythocholate (II). Its structure was elucidated as 3 alpha, 12 alpha, 16 alpha-trihydroxy-5-cholan-24-oic acid N-[2-sulfoethyl] amide by IR, 1HNMR, 13CNMR, MS 13C-1H COSY, and chemical reaction.


[Studies on the chemical constituents from the skin of Bufo bufo gargarizans Cantor].

Four bufotoxins were isolated by means of preparative reversed phase HPLC from the water soluble fraction of the skin of Bufo bufo gargarizans Cantor. On the basis of their spectral data (UV, IR, 1HNMR, 13CNMR, EIMS and FDMS), amino acid analyses and chemical properties, they were identified as bufotalin 3-succinoylarginine ester(I), bufalin 3-succinoylarginine ester(II), cinobufagin 3-succinoylarginine ester(III), and resibufogenin 3-succinoylarginine ester(IV). Compound I is a new bufotoxin.


[The effect of molecular volume and partition coefficient on percutaneous absorption].

A series of 8 p-aminobenzoate esters were selected as model drugs to study the effect of molecular volume and partition coefficient on percutaneous absorption. The octanol/water partition coefficient and solubility of these compounds were determined and their penetration rate through rat skin in vitro was measured using a Keshany-Chien diffusion cell. The results showed that when the molecular volume was increased the permeation coefficient was decreased. However, when the partition coefficient was increased, the permeation coefficient was increased at first and then reached a plateau. The mathematical formula has been derived from a bi-layer diffusion model to show how the molecular volume and the partition coefficient influence the permeation coefficient. The formula could be used to estimate the permeation coefficient of drug through skin.


[Determination of oleanolic acid in Achyranthes bidentata BLume and its preparations by supercritical fluid chromatography].

Capillary SFC was used for the determination of oleanolic acid in Achyranthes bidentata BLume and its preparations Tianmawan, Jinguishenqiwan and Hechedazaowan. The amount of oleanolic acid in the root of Achyranthes bidentata BLume was 1.75-2.19% (mean +/- SD = 1.94 +/- 0.17%). The limit of detection was 9.605 x 10(-11) g. The method is highly sensitive, accurate, reproducible, simple, rapid and specific, so, it can be extensively used for the determination of other preparations and crude herbs.


[On the correction of systematic errors of analytical methods used in the content uniformity test].

In this paper, the constant and proportional systematic errors of analytical methods for the content uniformity test were studied with reference to the accurate analytical method for the assay. Seven monographs of tablets admitted to USP(XXII), Ch P (1985, 1990) and JP(XI) were taken as cases in point and the systematic errors of two of them, i.e. digoxin and nitroglycerin tablets, were ascertained by the test of significance. To improve the accuracy of analytical methods for the content uniformity test, a correction formula more reasonable and convincing than that of USP (XXI, XXII) was proposed, and its theoretical basis described briefly.


[Zero-crossing derivative spectrophotometry for the determination of three components in paracetamol compound tablets].

The zero-order derivative absorption spectra of aspirin, paracetamol and caffeine are closely overlapping. In this paper, a zero-crossing derivative spectrophotometry combined with simultaneous equations is proposed for the determination of the three components in a mixture without the need of prior separation. Satisfactory results were obtained. The method is reproducible, accurate and rapid. Calculation is not complicated. This method could be applied to biological fluid analysis.


[A study on the decomposition kinetics of vitamin C tablet].

Under the condition of relative humidity less than the critical relative humidity, the discoloration rate and decomposition rate of vitamin C tablet and the discoloration rate of vitamin C tablet in solution were studied at temperatures 60-90 degrees C and relative humidities 60%-80%. The general equation of the relationship between the apparent rate constant k, absolute temperature T and relative humidity RH is: k = k' exp(-E/RT) exp(mRH), where k' and m are constants, E is apparent activation energy. The values of k', m and E for discoloration, decomposition and discoloration in solution are different.


[Study of the relationship between structure and anticonvulsant activities of 5-substituted-1-butry-3-pyrazolidinones and their synthesis].

According to the quantitative structure-activity relationship studies of 3-pyrazolidinones with different substituent on positions 1 and 5 reported previously, the anticonvulsant activity is parabolically related with the total fragment constent (Fr hydrophobic parameter) of the 1 and 5 substituents of 3-pyrazolidion. The optimum Fr was about 5.6. Therefore, eleven new 5-substituted-3-pyrazolidinones have been synthesized. Pharmacological test showed that they are all potent anticonvulsant agents. Among them 1-n-butyl-5-(p-chlorophenyl)-3-pyrazolidinone was shown to be the most potent so far synthesized.


[Synthesis of N-(4-substituted amino-4-oxobutyryl)-N-substituted glycines].

Nine N-(4-substituted amino-4-oxobutyryl)-N-substituted glycines expected to have inhibitory activity on angiotensin-converting enzyme were synthesized. All of the title compounds and their t-butyl esters were unreported in the literature. In preliminary test in rats, compounds V2, V6 and V7 showed marked hypotensive activity.


[Behcet's disease. Experience of an internal medicine service from 1982 to 1991].

The authors present the results of a retrospective study on Behçet's disease, concerning 19 patients observed in Medicine Service 2 (Santo António dos Capuchos Hospital) between 1982 and 1991. There were 15 male and 4 female patients, with a mean age of 33. The clinical manifestations were: oral--100%, ocular--100%, genital--89%, articular--79%, cutaneous--68%, general non-specific manifestations--52%, venous--26%, peripheral nervous system--21%, central nervous system--10% and persistent headaches--10%.


[Psychiatric morbidity in general hospital inpatients].

Psychiatric morbidity was studied in 73 patients of three Units (Medicine, Surgery and Obstetrics) of a general hospital (S. Francisco Xavier Hospital, Lisbon). In the first stage, the patients were clinically evaluated by their doctors. In the second stage, psychiatrists using the General Health Questionnaire (G.H.Q. 30) interviewed all the patients according to the clinical evaluation, 41% of the patients had a significant psychological disorder. However, very significant differences were found between the prevalence rates in the three units. As defined by the G.H.Q. 30, 50 patients (68.5%) had psychiatric disorders, which is statistically different from the results obtained through clinical evaluation. The depression and anxiety syndromes were the most frequent disorders. Organic mental disorders were less frequent and almost limited to medical patients. The results of this study confirm a high rate of psychiatric morbidity in the general hospital, although considerable differences exist between the three units included in the study. We can also conclude that many psychiatric disorders are not correctly identified. This fact, more frequent in units where there is a more brief doctor-patient relationship, supports the necessity of implementing liaison psychiatry programs.


[Depression as the sign of true self].

Referring to examples from the poetry of Fernando Pessoa and Mário de Sá Carneiro, we draw attention to the narcissistic relationship between mother and baby, to the role of the mirror-image of the mother's face, and to the organization of a false self caused by a deficiency both of that function, and of the narcissistic investment of the child. The false self is a defence mechanism which protects the true self. This may appear as a depressive state with a feeling of loss and emptiness. The depression is, in such cases, a sign and a clue which may lead to the revelation of the true self.


[Blood transfusion in sickle cell disease].

Sickle cell disease is a genetic disorder characterized by the presence of hemoglobin S. This hemoglobin has a low affinity for oxygen, allowing a good oxygenation of tissues with low levels of hemoglobin. Therefore, blood transfusions are not necessary to correct basal anemia, but are indispensable in the treatment and prevention of some complications. Detailed indications for blood transfusions are presented, as well as the different types of transfusion usually performed: simple, exchange and hypertransfusion. Finally, reference is made to the preferable blood components to be used, complications related with transfusion, the preventive measures to be taken and the need for a patient's transfusion record.


[Safety in hemophilia A treatment. Viral inactivation of FVIII:C concentrates].

In the last thirty years, factor VIII concentrates have been the mainstay of hemophilia treatment, first as wet cryoprecipitate and later as dry concentrates commercially available. The evidence of a high risk of blood-born virus transmission by these products provoked the development of new methods for virus inactivation. We report these methods with special attention to their safety, and mention the new perspectives of treatment with recombinant DNA FVIII:C and ultimately by gene insertion therapy.


[Evaluation of blood esterases in Alzheimer's disease].

The aim of this work was to evaluate a possible correlation between erythrocyte acetylcholinesterase activity (AChE) and membrane fluidity expressed by fluorescence polarization of--1,6--diphenyl 1,3,5--hexatriene (DPH). Blood samples of 34 Alzheimer's patients (18F and 16M) were obtained and haemoglobin concentration, haematocrit, plasma (butyrylcholinesterase, BuChE) and erythrocyte (AChE) esterase activities and fluorescence polarization after introduction of DPH in erythrocyte membrane have been determined. Results were compared with values obtained from blood samples of 34 apparently healthy volunteers with the same age variation (53-82 years). There was no correlation between AChE activity and fluorescence polarization in the control group nor in the patients' group. There was a significant negative correlation (r = -0.82; p < 0.001) between mean corpuscular hemoglobin concentration (MCHG) and erythrocyte acetylcholinesterase activity in Alzheimer's patients. This correlation suggests that any variation of internal globular viscosity (or MCHG) may indirectly affect AChE enzymatic activity and consequently contribute to the loss of interrelation between AChE activity and membrane lipid fluidity, verified in the present work. A biological marker for Alzheimer's disease diagnosis remains to be discovered.


[Drug surveillance: concepts, objectives, and methods].

Adverse reactions to drugs, by their frequency and morbidity, constitute a very important problem in clinical practice today. However, it is not always possible to establish the definitive causal relationship between the drug and the clinico-laboratory situation. This is not only due to the variability of these findings and the inherent difficulties of the methodology used, but also the fact that most doctors show little sensitivity to such an important subject. In this paper we present a short review of the drug surveillance programme: basic concepts, objectives and the most important methodology, as well as the current situation in the EEC countries.


[Research in child mental health].

Some considerations are made about current child psychiatry research and its future challenge. We analyse some studies about parental psychopathological influence in the early relationship, mentioning obstacles and advantages of some clinical and epidemiological research methods. We emphasize the value of interaction, observation and the use of videoscopy in infant clinical research. In Portugal, the lack of motivation to work in mental health research is an impediment to establishing clinical and training priorities.


[Ethics, health & society].

The sudden advent of new technological devices and sophisticated methods in both biological research and medical practice alerted different social groups to the development of unprecedented problems for moral counsel and decision-making. The field of study called bioethics grew out of religiously motivated concerns, but nowadays it attracts the attention of politicians, lawyers, religious thinkers, philosophers, scientists and doctors. Bioethics is becoming a sphere of interest to an increasing number of people. Each of these groups bring their own values, which are sometimes not in total agreement with the traditional values of medical ethics, to discussion. Therefore, the Author defends a more active participation of doctors through their representative bodies in the discussion of policies concerning the research and development of new technologies, and also the individual use of them when they are available, so that the practice of medicine may preserve the hippocratic legacy, accepting only the external influences when they are not in conflict with the intrinsic morality of medicine.


[Myxedema coma].

Five patients, 4 female and 1 male, aged 45 to 73, were observed in myxedema coma between 1984 and 1992. In three patients hypothyroidism was not known. Depressed consciousness, hypothermia, bradycardia and no goiter were common to all and a precipitating factor could be identified in 3 of them. Therapy included L-thyroxine and/or triiodothyronine by nasogastric tube, hydrocortisone and supportive measures. Outcome was good in the 2 patients with known precipitating event, less impaired consciousness and normalization of body temperature by the third day of treatment.


Hippocampal rhythmic slow activity (RSA) in the cat after intraseptal injections of muscarinic cholinolytics.

Influence of intraseptal injections of cholinolytics on hippocampal rhythmic slow activity (RSA) was investigated in cats. Results of the first experiment have shown that neither atropine (At) nor scopolamine (Sc) injected into the medial septum in doses of 20 micrograms prevented the induction of RSA by a cholinergic (carbachol-CCh) stimulation of the anterior hypothalamus as well as by electrical stimulation of posterior hypothalamus or periaqueductal grey substance (PAG), and were only partially effective in prevention of the spontaneous RSA. RSA did not appear spontaneously and could not be induced by electrical brain stimulation after intraperitoneal injections of At (2.0 mg/kg) or Sc (0.2 mg/kg). Results of the second experiment have shown that intraseptal injections of At (5.0 or 10.0 micrograms) are also ineffective in prevention of RSA induction by CCh (2.5 micrograms) injected into the same septal locus. The data suggest that the medial septum cannot be regarded as the common muscarinic link within the RSA generating system of the cat.


Pharmacological and physicochemical properties of collagen breakdown-products.

It has been found that the pharmacologically active, low molecular products obtained by digestion of telopeptides-deprived type I collagen with bacterial collagenase is a heterogenous mixture of at least 21 peptides of different molecular weight. They contain 3 to 15 amino acid residues. About 80% of them are tripeptides of the sequence Gly-Pro-X. The most abundant are two peptides: Gly-Pro-Hyp and Gly-Pro-Ala. The peptides injected into the lateral cerebral ventricle of the rat evoked some behavioral effects. They decreased the psychomotoric activity (evaluated with Lat's test) and increased the cataleptic action of haloperidol. On the other hand, they did not exert any effect on amphetamine-induced stereotypy and did not counteract the apomorphine-induced stereotypy.


The differences between simultaneously or separately tested instrumental sexual responses in rats.

The instrumental sexual responses were investigated in male and female rats in the following experimental situations: (1) when the instrumental responses were tested simultaneously in the male and the female (2) when the male was a subject and the female was used as a reward only, and (3) when the opposite was true. The analysis of the data indicated that if the instrumental responses were tested separately in male and female rats, the male response latencies were significantly shorter than the female ones, while during the simultaneous testing no such difference was observed. This phenomenon seems to be a result of avoiding by the male rat of the frustration which occurs during waiting for the female after accomplishing the instrumental response.


Asymmetry in visual evoked potentials to gratings registered in the two hemispheres of the human brain.

The study aimed at testing, by a visual evoked potential method, the hypothesis of the hemispheric specialization in processing of high and low-spatial frequencies. Twenty four right-handed subjects (12 males and 12 females) were presented with square-wave vertical gratings of various spatial frequencies (0.67, 0.86, 1.20, 2.00, 2.40, 3.00, 3.30, 6.00 and 7.50 c/deg). Gratings were presented in nine separate blocks each containing 64 exposures. Time of exposure was 30 ms and the interstimulus interval varied from 2 to 3.5 s. VEPs were recorded with electrodes located at O1 and O2 and referred to Cz according to the 10/20 system. Amplitudes and latencies of two VEPs components (N130-150 and P200-240) were analyzed. The results showed larger amplitudes of VEPs registered in the right hemisphere of both males and females. This difference, however, was apparent in the earlier component of VEPs in females and in the later component in males. The observed hemispheric asymmetry did not depend on the spatial frequency of grating. Females demonstrated longer latencies than males for both N and P components. Our data suggest that the right hemisphere predominates in processing grating stimuli, but the dynamics of this process differ in the two sexes. The results do not support Sergent's hypothesis which postulate the right hemisphere specialization for low spatial frequencies and the left hemisphere specialization for high spatial frequencies.


Hemispheric asymmetry in event related potentials associated with positive and negative emotions.

Event-related potentials from symmetrical points of the left and right frontal and occipital cortex were recorded while subjects experienced positive and negative emotions. The emotions were elicited by either missing or hitting a target with a photoelectric gun. Twenty three right-handers (10 males and 13 females) were tested. Each subject took part in two sessions. In the first session the subjects were informed about their performance (hit or miss) after each shot. In the second, control session, no feedback was given. The amplitudes of P180 potential registered from the occipital cortex were higher in the right than in the left cerebral hemisphere, irrespectively of subjects' performance (i.e. a miss or a hit). No such tendency was observed in potentials registered from the frontal cortex. These regularities emerged only in the feedback situation, i.e. when subjects were informed about their performance, although higher ERPs were registered for hits than for misses. The results support the hypothesis that the posterior region of the right hemisphere is more engaged than the left one in experiencing emotions, irrespectively of their sign.


Response strategy in two-choice visual discrimination in the rabbit.

Rabbits were trained to discriminate striated patterns of different orientation in a two-choice discrimination box. After the 90% correct level had been reached, motor behaviour was studied during visual discrimination. It was found that the animals made their decision after seeing one of the two stimuli. This finding is in disagreement with an earlier study from which it was concluded that the animal's choice is mainly controlled by the unrewarded stimulus (Van Hof and Van Hof-van Duin 1984).


The role of calcium in the regulation of melatonin biosynthesis in the retina.

Vertebrate retina rhythmically produces melatonin, a hormone involved in the regulation of several intraocular processes cued by environmental lighting conditions. Calcium ions play an important role in the induction process of serotonin N-acetyltransferase (NAT), a key regulatory enzyme in melatonin biosynthetic pathway. The physiological, i.e. nocturnal, increase of NAT activity in the retina depends on transmembrane transport of Ca2+ through the L-type of voltage-sensitive calcium channels. It is suggested that Ca2+ may regulate NAT activity indirectly, by affecting the intracellular cyclic AMP content, which is, in turn, critical in the regulation of melatonin biosynthesis. The mode and mechanisms of Ca2+ action on processes governing melatonin formation in the retina are discussed.


[Dopaminergic neurons and clinical neuropsychiatry].

The neurobiologic acquisitions in the realm of the dopaminergic neurons are analyzed and discussed in connection with related clinical problems. Both "neurological" (extrapyramidal; autonomic; neuro endocrine) and "psychiatric" (bradifrenia; dissociation; depression of mood) symptoms and syndromes--whose pathophysiology and pharmacotherapy involves dopaminergic transmission--are discussed. The peculiar physiological meaning of dopaminergic neurons between the monoaminergic adaptive systems is stressed.


The use of EEG activating procedures in epileptology.

Epileptic seizures and EEG interictal paroxysmal activity (PA) usually occur in an apparently unpredictable fashion, and a small number of patients with truly epileptic seizures may not present any PA on repeated EEGs. With the aim of increasing the possibility of recording interictal or ictal PA, several activation procedures are routinely carried out. In rarer instances, seizures seem to be more or less specifically evoked by unusual triggering procedures, or are chronologically related to biological rhythms. These different activating procedures may have different effectiveness depending on the type of epileptic syndrome. In the present paper the Authors describe the different activating procedures, both routinely employed and unusual ones. Their possible differential use with regard to the different epileptic syndromes and to the specific epileptologic history of the patient are examined. A selective use of these procedures is suggested, as an accurate choice of such techniques may increase the diagnostic usefulness of the EEG, in particular in patients whose basal recording is not contributory.


Photoparoxysmal response on eye closure in photosensitive patients.

The Authors studied the presence of photoparoxysmal response (PPR) during intermittent photic stimulation (IPS) in 2,888 consecutive EEG recordings. PPR was present in 2.3% of EEGs and 10% of all patients referred to EEG laboratory for epilepsy (45 patients, 18 males, 27 females (M:F ratio 1:1.5), mean age 12 yrs). In 24 (53.3%) of these patients PPR was evident only (24.4%) or strikingly (28.9%) on eye closure during IPS. In 7 patients no other epileptic abnormalities were found on basal EEG and during hyperventilation, nor during IPS with eyes closed and with eyes open. The Authors consider the eye closure during IPS the most useful method to reveal a PPR in photosensitive patients and believe that a good IPS technique must include this procedure in the routine EEG examination.


"Memory-scanning" event-related potentials. Correlations with verbal and performance scores.

Auditory and visual event-related potentials (ERPs) to a digit probe identification task in a modified Sternberg paradigm have been compared with psychological tests of verbal and performance ability (WAIS) in 19 healthy subjects. We have found a significant correlation between ERP amplitude and test scores. The higher the scores the "more negative" the responses. Correlations were stimulus-modality dependent. Auditory and visual ERPs were strongly correlated with "verbal" and "performance" IQ, respectively. The characteristics of these IQ-dependent electrophysiological features suggest that they may be related to the ability to allocate attention.


In vivo administration of propranolol decreases exaggerated amounts of serum TNF-alpha in patients with migraine without aura. Possible mechanism of action.

Patients with migraine without aura (MWA) display elevated amounts of Tumor Necrosis Factor (TNF)-alpha in their sera. In this study in 18 patients with MWA the in vivo effect of propranolol, a beta blocker agent, was evaluated with regard to the TNF serum levels before and after treatment. Results show that in 9 out 11 patients exaggerated serum concentrations of TNF reverted to normality after three months of therapy. Some hypotheses on the mechanisms of action of propranolol in terms of modulation of the immune response are formulated.


Cytokines in the pathogenesis of multiple sclerosis.

The authors evaluate the involvement of various cytokines (interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha and gamma-interferon) in the pathogenesis of multiple sclerosis. The cytokines might participate in nervous tissue damage by promoting demyelination and oligodendrocyte injury or by enhancing local immune response. In addition, several authors reported increased levels of some cytokines in serum and cerebrospinal fluid of patients with multiple sclerosis. These findings suggest that cytokines can play a significant role in the immunopathogenesis of the disease.


Acute effect of flunarizine on saccadic eye movements.

It has been postulated that flunarizine (FNZ) acts on the brain through a stabilizing effect on membrane electrical activity of neurones. It has been also suggested that neurogenic events characterized by an increased tendency of nerve cells to fire, could be involved in the pathogenesis of migraine and epilepsy. The study was aimed to assess the effect of a single oral dose of FNZ (20 mg) on CNS specific functions by means of computer analysis of saccadic eye movements. The study was performed on six healthy volunteers according to a double-blind, cross-over, placebo controlled design. FNZ produced a significant reduction only of peak saccadic velocity, thus suggesting a rather specific and selective effect on the burst cells of the para-median pontine reticular formation.


[Clinical and electrophysiological findings in various hereditary sensory neuropathies].

An electrophysiological study, comprehensive of peripheral sensory and motor conduction velocity (SCV, MCV), motor cortical stimulation (CS), median nerve somatosensory evoked potentials (SSEPs), brainstem evoked potentials (BAEPs) and sural nerve biopsy, was performed on 100 hereditary ataxia patients: 48 with Friedreich's ataxia (FA), 18 with Early Onset Cerebellar Ataxia (EOCA) and 34 with Autosomal Dominant Cerebellar Ataxia (ADCA). An early "peripheral" and "central" sensory impairment was observed in FA probably due to axonal loss and not related to disease severity or duration. On the contrary, BAEP and CS findings suggested a progressive involvement of the auditory and motor pathways. The presence of a non progressive sensory neuropathy allowed a distinction of EOCA patients in two groups: with and without peripheral neuropathy. The clinical and genetic heterogeneity was confirmed by the variability of evoked potential results. The ADCA patients showed the mildest degree of electrophysiologic abnormalities with an involvement of the peripheral pathways, both sensory and motor, more frequent than the central ones.


Evoked potentials in brain death. A critical review.

The development of transplant surgery has determined the necessity to revise criteria and to apply new electrophysiologic techniques to add further informations when survival of brain function is in question. The EPs, which provide a sensitive tool for assessment of integrity of main sensorial systems, could have a place in the electrophysiologic evaluation of the brain death. This review deals with the role of EPs in brain death and points out the main patterns found in that clinical condition.


Plasma exchange and i.v.-immunoglobulins: new approaches to the treatment of Guillain-Barre' syndrome.

We report the results obtained with plasma exchange (PE) in 26 patients (18 males, 8 females) with Guillain-Barré Syndrome (GBS) of maximal severity and also the results with IVGG in 7 patients (3 males, 4 females) where PE could not be employed. A complete clinical and neurophysiological evaluation was carried out. A follow-up was effected at regular intervals for a year. From this study the efficacy of PE in GBS was confirmed and a correlation was found between the amplitude of the muscular potential registered in the acute phase and the prognosis of the illness. PE is not effective for patients with a fulminant course and blocking of conduction. Good results have been obtained with IVGG therapy, which seems to be safe and effective whenever PE is not possible.