Determination of sodium cromoglycate in pharmaceutical dosage forms using TLC-densitometry.

A TLC-UV densitometric method for the determination of sodium cromoglycate (SCG) in ophthalmic solutions, gels and capsules has been developed. After TLC separation of active substance on silica gel GF254 using methanol-water-ethylacetate (15:45:40 v/v/v) as the mobile phase, densitometric measurements were performed with HPTLC scanner at 254 nm. The proposed method is rapid and simple, free from interference by adjuvants and can be suggested for the routine analysis of sodium cromoglycate.


[Textual study of Chinese drug loulu].

Through a critical study of Loulu in ancient Chinese herbals, it is concluded that the botanical origin of Loulu should be Qizhou Loulu, the dried root of Rhaponticum uniflorum of family Compositae, while the dried root of Echinops latifolius, which is also one of the species specified in Chinese Pharmacopoeia, should not be used as Loulu because of its deficiency of herbal evidences and totally different chemical constituents from those of the former. It is therefore recommended the latter plant be deleted from the Chinese Pharmacopoeia.


[Pharmacognostical studies on two species of Chinese drug caowu produced in Sichuan].

This paper deals with 2 species of medicinal roots of Aconitum legendrei and A. geniculatum which are used in Sichuan as Caowu. The morphological and histological characteristics of these two roots are described.


[Experimental studies on growing seedlings of Morinda officinalis How].

By using the techniques of growing seedlings in bowshaped shed covered with plastic sheeting plus treatment with plant growth regulator, vegetative and generative propagation tests have been made of Morinda officinalis. Scientific evidences have thus been provided for growing seedlings of Morinda officinalis.


[Effect of the root of Polygonum multiflorum Thunb. and its processed products on fat accumulation in the liver of mice].

Experiments have shown that the root of Polygonum multiflorum exhibits inhibitory effect on triglyceride (TG) accumulation in the liver of mice induced by CCl4, cortisone acetate and thioacetamide (TAA). Its processed products (I, II) were found to be effective in lowering the accumulated TG induced by cortisone acetate. The root of Polygonum multiflorum and its processed products also reduced the enlargement of liver by CCl4.


[Synchronized control of specific gravity, drug contents and recovery rate of inspissated extracts].

As a result of experimentation we have developed a method that helps to synchronize the control of the three preset criteria, i.e. specific gravity, drug contents and recovery rate, in the process of preparing traditional Chinese medicines. Simple and easy to use, the method is also good for similar purposes in the preparation of traditional Chinese syrups.


[Research on sterilization of pathogens by high electrostatic voltage method].

An experimental research has been carried out on the sterilization of four kinds of pathogens by high electrostatic method along with an inquiry into the influence of voltage waveform and the treated time on sterilization. It is concluded that pathogens can be killed efficiently by corona discharge field.


[Saponins in the fruit pedicels of Panax notoginseng (Burk.) F.H. Chen (continue)].

Six saponins were isolated from the fruit pedicels of Panax notoginseng. Five of them were identified as gypenoside-XVII, -XV, ginsenoside-Rb1, and notoginsenoside-Fc, -Fa on the basis of chemical methods, spectroscopic analysis and comparison with authentic standards. Quantitative determination of the major saponins in fruit pedicels from the plant was made by thin layer chromatography-densitometry.


[Chemical constituents of Hedysarum polybotrys Hand.-Mazz].

Butanedioic acid was isolated from the ethyl alcohol extract of Hedysarum polybotrys. The methylated carboxylic acid was identified by GC-MS method.


[Anti-inflammatory and analgesic actions of artificial and fermentative Ganoderma sinense (AFGS)].

Both AFGS and natural Ganoderma sinense (NGS) have obvious anti-inflammatory and analgesic effects for arthritis in rats induced by carrageenan and the pain reaction in mice induced by hot scalding as well as HAC-induced writhing. AFGS also can reduce the edematous swelling of mice's ears, reduce the capillary permeability of mice skin and obviously inhibit cotton pellets granuloma implanted in rats. It can promote cytophagy capacity of the reticular endothelial cells in mice. No irritation on the gastric mucosa in rats has been observed.


[Pharmacokinetics of liensinine in rabbits].

A method for the determination of plasma concentration of liensinine with HPLC and pharmacokinetic study of liensinine in rabbits were reported. Assay linearity was shown over the range of 0.125-2.5 micrograms/ml serum with regression coefficient of 0.9997. The mean recoveries of liensinine in plasma (within-day and between-days) were all more than 99% of the dose and the coefficients of variation were less than 5%. After a single intravenous injection of liensinine 6mg/kg to rabbit. The pharmacokinetic characteristics were found to fit a two-compartment open model. Important parameters were: t1/2 alpha = 8.303 min t1/2 beta = 129.960min AUC = 132.67 micrograms.min/ml CL = 0.045 L/min Vc = 2.768 L/kg.


[The protective effect of Hippophae rhamnoides L. on hyperlipidemic serum cultured smooth muscle cells in vitro].

The effect of Hippophae rhamnoides on hyperlipidemic rabbit serum (HRS) cultured smooth muscle cells (SMC) was observed in comparison with vitamin E(VE). The results show that Hippophae rhamnoides, much like VE, is also a potent antioxidant. It strongly decreases the MDA content in HRS cultured SMC and protect the cells from the injury of lipid peroxidation, and thus keeps the SMC growing and proliferating health. The results implicate that Hippophae rhamnoides is an effective antioxidant, and one of the important mechanisms of Hippophae rhamnoides in anti-atherosclerosis reported recently may be closely related to the action of anti-lipid peroxidation.


Furan and thiophene analogues of omeprazole.

Synthesis and structure of some analogs of the omeprazole containing furan and thiophene rings are reported. Their effects on the basal and the histamine-stimulated secretion were evaluated on the isolated rat stomach.


Chemical stability of insulin. 4. Mechanisms and kinetics of chemical transformations in pharmaceutical formulation.

Insulin decomposes by a multitude of chemical reactions [1-3]. It deamidates at two different residues by entirely different mechanisms. In acid, deamidation at AsnA21 is intramolecularly catalyzed by the protonated C-terminal, whereas above pH 6 an intermediate imide formation at residue AsnB3 leads to isoAsp and Asp derivatives. The imide formation requires a large rotation around the alpha-carbon/peptide carbonyl carbon bond at B3, corresponding to a 10 A movement of the B-chain N-terminal. The main determinant for the rate of B3 deamidation, as well as for the ratio between the two products formed, is the local conformational structure, which is highly influenced by various excipients and the physical state of the insulin. An amazing thermolysin-like, autoproteolytic cleavage of the A-chain takes place in rhombohedral insulin crystals, mediated by a concerted catalytic action by several, inter-hexameric functional groups and Zn2+. Intermolecular, covalent cross-linking of insulin molecules occurs via several mechanisms. The most prominent type of mechanism is aminolysis by the N-terminals, leading to isopeptide linkages with the A-chain side-chain amides of residues GlnA15, AsnA18 and AsnA21. The same type of reaction also leads to covalent cross-linking of the N-terminal in protamine with insulin. Disulfide exchange reactions, initiated by lysis of the A7-B7 disulfide bridge, lead mainly to formation of covalent oligo- and polymers. Activation energy (Ea) for the neutral deamidation and the aminolysis reactions was found to be 80 and 119 KJ/mol, respectively.


Chemical stability of insulin. 5. Isolation, characterization and identification of insulin transformation products.

During storage of insulin formulated for therapy, minor amounts of various degradation and covalent di- and polymerization products are formed [1-3]. The main chemical transformation products were isolated from aged preparations and characterized chemically and biologically. The most prominent products formed in neutral medium were identified as a mixture of deamidation products hydrolyzed at residue B3, namely isoAsp B3 and Asp B3 derivatives. A hydrolysis product formed only in crystals of insulin zinc suspensions containing a surplus of zinc ions in the supernatant was identified as an A8-A9 cleavage product. The small amounts of covalent insulin dimers (CID) formed in all formulations were shown to be a heterogenous mixture of 5-6 different CIDs with a composition dependent on the pharmaceutical formulation. The chemical characteristics of the CIDs indicate that they are formed through a transamidation reaction mainly between the B-chain N-terminal and one of the four amide side-chains of the A chain. GlnA15, AsnA18 and, in particular, AsnA21 participate in the formation of such isopeptide links between two insulin molecules. The covalent insulin-protamine products (CIPP) formed during storage of NPH preparations presumably originate from a similar reaction between the protamine N-terminal with an amide in insulin. Covalent polymerization products, mainly formed during storage of amorphously suspended insulin at higher temperature, were shown to be due to disulfide interactions. Biological in vivo potencies relative to native insulin were less than 2% for the split-(A8-A9)-product and for the covalent disulfide exchange polymers, 4% for the CIPP, approximately 15% for the CIDs, whereas the B3 derivatives exhibited full potency. Rabbit immunization experiments revealed that none of the insulin transformation products had significantly increased immunogenicity in rabbits.


Relative bioavailability in man of noscapine administered in lozenges and mixture.

The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture.


The limbic system: a review of its empirical foundation.

The concept of the limbic system is highly influential in many areas of the neurosciences and in their applications to clinical medicine. The value of this concept has been questioned, denied, and defended several times in the past but a comprehensive critical evaluation has never been published. In this article we take several approaches to analyse empirical data of relevance to the limbic system. First we delineate its factual application in different areas. The limbic system has a very wide scope and divergent use. Secondly we extract criteria for its definition from research literature using the bibliographic database Medline. The limbic system has been defined variously on a number of different descriptive levels from morphology to behaviour. Thirdly we review its empirical foundations comparing evidence from different sources. The limbic system lacks an adequate empirical definition in spite of numerous efforts. Last we evaluate its construction as a scientific concept from empirical facts. The limbic system is a non-empirical explanatory concept for poorly understood brain functions. We conclude that the concept of the limbic system cannot be accepted on empirical grounds. However, it is a very attractive concept in the search for explanation of brain function. The non-empirical contents of the limbic system remains largely unexplored.


Can rats solve a simple version of the traveling salesman problem?

Whereas correct tours through the radial arm maze are almost equally long, free choice mazes with multiple goals scattered in an open field allow the animal to select the shortest one from a multitude of correct tours. Thirteen rats were trained (at 10 trials per day) to visit an array of cylindrical feeders in an open field (40 x 100 cm) with reward available only when visiting the last feeder of the set. In Expt. 1 with eight feeders arranged in five different configurations the rats made after 10 days of training 1 error in the first 8 choices and incidence of errorless trials was about 20%. In Expt. 2. the use of six feeders in a rectangular (A) or double triangle (B) configuration increased the incidence of errorless trials to 60%. Expt. 3 showed that performance in the 6-feeder maze was significantly impaired by 6 mg/kg ketamine or 0.25 mg/kg scopolamine but not by lower dosages of these drugs. Tours generated on errorless trials (each feeder visited only once) during 10 days of Expt. 2 were analyzed. Six places can be visited in 6! = 720 different closed tours the lengths of which (in arbitrary units) range from 6.00 to 10.12 for A and from 6.83 to 10.47 for B. Whereas random generation of correct routes yielded only 5% of the shortest tours, they were clearly preferred by rats (41% in A and 45% in B). The apparent proficiency of rats in this optimization problem is probably not due to cognitive comparison of the possible correct routes but rather to following a simple rule 'Always go to the nearest not yet visited feeder'.


The ontogenesis of sensorimotor reflexes in the Mongolian gerbil Meriones unguiculatus.

The ontogeny of a number of sensorimotor reflexes has been studied in the Mongolian gerbil. In contrast to a number of other mammals, the gerbil has relatively long and strong hindlimbs but small forelimbs, indicating their different importance for a number of locomotor acts, and during the developmental period studied, the hindlimbs grow at a much faster rate than the forelimbs. The following sequence of appearance and maturation of the reflexes was observed: rooting, forelimb hopping, surface body righting, forelimb grasp, hindlimb hopping, chin tactile placing, visual placing, air body righting and, at the same time, forelimb and hindlimb tactile placing. This sequence concords with the general gradient of development and maturation of the spinal and brain centers subserving these reflexes, as evaluated from Nissl preparations. The results indicate that there is no clearcut rostro-caudal gradient of postnatal maturation of the spinal cord and the spinally mediated reflexes, but that there is a general caudo-rostral gradient of brain maturation and of the brain-mediated reflexes. Comparisons with other mammals are made.


Behavior-related cortical activity and swim-to-platform performance in the aged rat.

Aged rats (26 months) usually retained normal acetylcholine-dependent and serotonin-dependent forms of neocortical low-voltage fast activity and serotonin-dependent hippocampal rhythmical slow-wave activity. In a simple swim-to-platform test, aged rats (23 and 26 months) performed normally in acquisition and in retention over a 7-day period. The results are discussed in relation to the common assumption that aged rats provide a valid model of human senile dementia.


Classical conditioning after temporal lobe lesions in man: sparing of simple discrimination and extinction.

Recent reports of impaired conditional discrimination learning in temporal lobectomy subjects have raised the question of response inhibition deficits in these patients. In the present study, left and right temporal lobectomy subjects and healthy controls completed an eyelid conditioning task, which required simple two-tone discrimination learning, followed by extinction. There were no group differences with regard to discrimination learning or extinction. General deficits in response inhibition are therefore not likely to account for the impairment in conditional discrimination observed in temporal lobectomy patients.


The effect of imagery perspectives on the psychophysiological responses to imagined exercise.

The effect of imagery perspectives, i.e. internal imagery vs. external imagery, on the psychophysiological responses to imagined exercise was investigated in the present study. Thirty male and female college students were randomly assigned to perform either internal imagery, external imagery or simple rest in addition to actual exercise. Metabolic, cardiovascular and perceptual responses were recorded before, during and after imagined exercise, actual exercise and rest. The results indicated that internal imagery resulted in a significant increase in ventilation and this response differed from the control condition. Effort sense was higher with internal imagery compared with external imagery. However, both internal and external imagery produced significant elevations in systolic blood pressure (SBP) from pre- to post-imagery, and these values were identical to those observed with actual exercise. Therefore, some responses to imagery were like those seen during actual exercise. Oxygen consumption (VO2), respiratory rate (RR), respiratory exchange ratio (RER), heart rate (HR) and diastolic blood pressure (DBP) were similar between internal and external imagery. It is concluded that the psychophysiological responses to internal imagery resemble actual exercise more than external imagery.


Sexual behavior enhances postictal behavioral depression in kindled rats: opioid involvement.

Past research has demonstrated brain opioid and GABA release in response to ejaculation. In the present study we evaluated the potential role of these neurotransmitters in the postictal behavioral depression (PBD), after-discharge (AD) duration, and seizure intensity in rats kindled in the medial preoptic area (MPOA) and amygdala (AMG). The PBD, the AD duration and the seizure intensity were measured after a standard kindling stimulus and after a standard kindling stimulus applied 2 min after ejaculation. The PBD was significantly increased when the animals were stimulated 2 min after ejaculation. This increase was found in MPOA- but not in AMG-kindled rats. Ejaculation had no effect on AD duration or seizure intensity. Naloxone administration before the initiation of sexual behavior completely blocked the increase in PBD in MPOA-kindled rats. It is suggested, by indirect evidence, that opioid release during sexual behavior is added to the release associated with kindled seizures, increasing the duration of the PBD. Since sexual behavior lacked effect on AD duration or seizure intensity, no evidence could be found suggesting that functionally relevant amounts of GABA are released during this behavior.


The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation.

A two-lever choice paradigm with concurrent variable interval schedules of reward was used to measure the growth in the subjective magnitude of reward as a function of current, by finding the adjustment in the stimulating current required to offset a given difference in the rates at which two rewards were received. Increasing current by a factor of 2 increased subjective reward magnitude by a factor ranging from as little as 3 to as much as 4,000. This range was about as great between electrodes within one rat as between electrodes and rats. In the light of earlier findings regarding the equivalent effects of increments is current and pulse frequency, these large differences cannot readily be explained by differing fiber densities at the site of stimulation. It is suggested that the medial forebrain bundle terminates in more than one spatio-temporal integration mechanism. The magnitude of the spatio-temporally integrated effect of a barrage of action potentials in the reward-relevant axons depends on which subset of reward-relevant axons is excited by the stimulation.


[Morpho-functional considerations on the annulate lamellae of the human oocyte].

Ovarian biopsy specimens from four girls in complete remission state of acute lymphoblastic leukemia, previously treated with antiblastic chemotherapy for about three years, were examined by means of electron microscopy. The normal morphology of residual follicles and, in particular, the observation that annulate lamellae were always present in oocytes of primordial and primary follicles, gave the chance to consider a possible functional role and to suggest a prognosis for future fertility. The similarities in structure to the nuclear envelope and the relation between annulate lamellae and other cellular organelles (especially endoplasmic reticulum and ribosomes) suggest that lamellae may be involved in the release, assembly or activation of stored development information. The annulate lamellae could prove to be an important organelle that participates in the regulation of gene expression. Therefore, the presence of annulate lamellae in oocytes of primordial and primary follicles may present the possibility of a normal development for these cells in which long-lived gene products are synthesized and transported to the cytoplasm for storage and use later in development. The above hypothesis, while leads to consider these patients at risk for low fertility and early menopause, does not consider them as definitely infertile.


[Intramural ganglia of the human gallbladder: morphological and functional observations].

The purpose of this study was the reinvestigation of the intrinsic innervation of human gall bladder with an immunohistochemical technique named peroxidase anti-peroxidase (PAP). The antigen demonstrated was the S100 protein normally present in the surface of glial cells, Schwann cells and satellite cells in ganglia. The tissues used were taken from 20 human gall bladders, fixed after surgery. This technique is not specific to demonstrate adrenergic or cholinergic innervation but it reveals just myelinated fibers. The current study was undertaken in order to study the organization and the function of plexus of nerves and ganglia present in the wall of the gall bladder. The neck of the gall bladder was the region in which the higher number of nerve cells and nervous fibers was present. The technique used has demonstrated ganglionated plexus and nerves in submucosal layer, fibromuscular and adventitial layer according to the enteric nervous system. All ganglia are postganglionic stations related with preganglionic cholinergic fibers. These results confirm that the intramural ganglia of the gall bladder are analogous to those of the enteric nervous system according to their common origin.


[Macronuclear DNA and total protein contents of mating types I and II of Paramecium primaurelia, during the phase of maturity and the transition to senescence. Preliminary observations].

Concerning the studies on mating type differentiation and life cycle development in Paramecium primaurelia stock 90, both macronuclear DNA and total protein contents have been measured cytofluorometrically in mating type I and mating type II isogenic cell lines growing in logarithmic phase, throughout their maturity period and transition to senescence. The target was to investigate whether the two mating types undergo clonal decline in different times, as the previous studies suggested. The results indicate that, throughout the maturity period, macronuclear DNA and total protein contents vary both in mating type I and mating type II cell lines; moreover, aged phenotypes as the dramatic decrease of both contents, firstly occur in mating type II which, therefore, appears to be submitted to clonal decline before mating type I.


Food ingestion and egestion in mating reactive populations of Paramecium primaurelia.

The study of food ingestion and egestion carried out on Paramecium primaurelia mating reactive cells shows that, after their transfer into a medium with suspended particles, the complementary mating type cells exhibit very significant differences in the food vacuole formation and egestion rate. Under the same external environmental conditions, the mating type II cells form and egest a higher number of food vacuoles when compared with mating type I cells. The higher rate of food vacuole formation shown by the mating type II cells is related to their faster growth rate.


[Mixed-function oxidase induction as a test for the biological monitoring of water: limitations and prospects].

The induction in fish liver of some enzyme activities, and typically of microsomal mixed-function oxidases (MFO), provides the earliest biological warning signal of exposure to pollutants. Our studies provided evidence that the basal levels of cytochrome P-450 and specific MFO activities, such as arylhydrocarbon hydroxylase (AHH) and ethoxyresorufin deethylase (EROD), were strongly influenced by the diet in freshwater fish (Oncorhynchus mykiss). The response of fish liver to a known enzyme inducer, i.e., beta-naphthoflavone, was also affected by the diet, which therefore should be carefully controlled in laboratory studies. Under field conditions MFO activities were significantly enhanced in the liver of O. mykiss kept in polluted river water as well as in the liver of the seawater fish Diplodus annularis collected from a polluted harbour area, as compared to specimens of the same species collected from an unpolluted reference area.


[Cytogenetic damage in fish (Oncorhynchus mykiss) exposed in situ to water from a polluted river].

Specimens of rainbow trout (Oncorhynchus mykiss) were exposed in situ for 7, 15, and 30 days to the water of the Po River either upstream or downstream the immission of the Lambro River, a small affluent which is highly polluted with industrial wastes. A third group of animals was maintained as control in aquarium with a flow of unchlorinated fresh water. Blood smears were obtained from each of the 90 trout specimens and examined under the microscope. The number of micronucleated erythrocytes (MNE) was registered by scoring at least 2,000 cells per animal. No increases in the number of MNE was detected in the animals exposed upstream the confluence, as compared to controls. Conversely, a significant increase in the frequency of MNE after 7 days of exposure to the water of the downstream site was observed. This frequency remained elevated, yet not significantly, after 15 and 30 days of exposure. This study demonstrates the validity of in situ exposure and the usefulness of cytogenetic end-points for environmental biomonitoring.


[Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 1) Studies during normal sodium and potassium balance].

We have investigated the effective role of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in normal potassium balance in both absence (N3) and presence of E (N3.E). All subjects were submitted to normal dietary intake of sodium (150 mmol/d) and potassium (50 mmol/d). The basal values of PRA, urinary aldosterone and plasma electrolytes were in the normal range. The only significant effect produced by E was a reduction in mean arterial pressure, without significant changes in creatinine cl., urinary hydro-electrolyte excretions as well as urinary excretions of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)


[Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 2) Studies during moderate potassium depletion].

We have investigated the relative roles of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in potassium depletion in both absence (D4) and presence of E (D4.E). Potassium depletion was induced by adaptation to a normal sodium (150 mmol/d) and low potassium (< or = 10 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. The cumulative potassium deficit achieved at the end of the depletive treatment was 214 +/- 54 mmol. This treatment induced significant decrease in basal plasma potassium concentration and increase in PRA without affecting urinary aldosterone and plasma sodium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


[Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 3) Relative roles of angiotensin II and prostanoids in early hypokalemic dysfunction].

We have investigated the relative roles of some renal prostanoids and angiotensin II in the hypokalemic renal dysfunction. To this aim we have evaluated the renal function in healthy women in induced potassium depletion of moderate degree before and after acute inhibition of cyclooxygenase (indomethacin, I) or angiotensin converting enzyme (enalapril, E). The renal function was explored by clearance (cl.) method during hypotonic polyuria induced by oral water load followed by 5% dextrose solution infusion; the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Potassium depletion was induced in 12 subjects by adaptation to low potassium (< or = 10 mmol/d) and normal sodium (150 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. In 6 subjects paired functional studies were performed in absence (D3) and presence of I (D3.I), 100 mg administered i.m. immediately before the water load. In other 6 subjects, paired studies were performed in absence (D4) and presence of E (D4.E), 10 mg administered per os 1 hour before the water load. No significant difference between D3 and D4 was observed as regards the potassium cumulative deficit as well as the basal values of plasma potassium concentration and plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliability and upper normal variability limits of pattern reversal visual evoked potential parameters.

Twenty healthy volunteers aged 21-48 years (10 males, 10 females) were submitted to pattern reversal visual evoked potentials with 15' and 30' checks. The recordings were repeated after 7 days to assess reliability and upper normal variability limits of the following parameters: latencies of N70, P100, N140 and peak-to peak amplitudes of N70-P100, P100-N140. Reliability was tested with intraclass correlation coefficient, which was excellent or good for all parameters. Test-retest variability limits were computed with = 0.01 for absolute latency differences and relative amplitude differences.


Study of 4-NQO induced mutations at the HPRT locus in CHO cell lines. Possible influences of preferential DNA-repair on the mutational spectrum.

In the attempt to determine the possible influence of excision repair processes on 4-NQO mutational spectra in mammalian cells, 4-NQO-induced mutants at the hprt locus were isolated in excision repair proficient (AA8) and deficient (UV5) CHO cell lines. DNA sequencing data on these mutants revealed that DNA repair may indeed modulate the induced mutational spectrum. In particular, more splice mutations were found in the repair proficient than in the repair deficient cells. This can be interpreted by a difference in repairability of the two principal 4-NQO G-adducts or by the existence of a transcription-coupled DNA preferential repair process.


Sex, race, age, and violent offending.

Although there is an increase in attention being paid to race and sex variations in crime and delinquency, little has been done to disaggregate the "gender-ratio" problem in order to account for participation in particular offenses, specifically different types of violent crime. Virtually all of the research pertaining to the interaction of gender, race and -violent crime focuses on murder and dichotomizes race into white and black, or white and nonwhite. This paper uses New York City arrest data to examine the extent of violence within various race-sex-crime subgroups. Rates of violent offending (i.e., homicide, robbery, assault, and burglary) are presented for black, Hispanic and white males and females. Regardless of violent crime type, black and Hispanic females exhibited high rates of offending relative to white females. Furthermore, the violent offending rates of black females paralleled those of white males. These findings suggest that an examination of gender differences in violent offending, independent of race, will produce incomplete and potentially misleading interpretations. The paper also provides a social structural explanation of the disproportionate involvement of black females (and males) in violent crime.


Patterns of homicide among the elderly.

Forty-five homicide offenders aged 55 and older are analyzed in the contexts of their deadly acts. Analyses include demographic and social characteristics of offenders and victims, demographic and social relationships between offenders and victims, circumstances of offense, and arrest disposition. Where feasible, comparisons are made with age-general populations of homicide offenders. Explanatory insights based on the "routine activity approach are offered.


Attitudes and practices of doctors toward spouse assault victims: an Australian study.

The attitudes and practices of 96 doctors toward spousal assault victims in the Australian Capital Territory, Australia, were investigated by questionnaire surveys distributed to general practitioners. The results indicate that although most doctors believe that members of their profession should play a role in prevention and treatment, many doctors may be failing to do so. In general, the sample was fairly homogeneous attitudinally, although long-serving practitioners tend to have more conservative attitudes about the causes of spousal assault and about doctors' role in prevention; and female doctors have more liberal beliefs than males about some aspects of causation and intervention. However, the latters' responses are less sympathetic when questioned about their own feelings and practices. Very few of the doctors had received any training on domestic violence issues, and for those that had, such training was minimal. There is nevertheless an indication that training has influenced some beliefs. The findings are not surprising in the context of the historical and current Australian ethos which perpetuates traditional gender stratification and wife battering.


Coping capacity among women with abusive partners.

Coping capacity, although increasingly implicated as a mediating force in how individuals respond to personal threat, is an underrecognized factor in work with women of abusive partners. To explore the utility of coping capacity as a multivariable set to guide intervention with women of abusive partners, findings are reported comparing four groups of women: those whose partners do not engage in abuse, are abusive toward them, are sex offenders of children for whom the woman is a parent, or are offenders of children for whom the woman is not a parent. Three variable sets were included: vulnerability factors that may negatively influence appraisals of threat and ability to cope with abuse; coping responses that include cognitive, emotional, and behavioral reactions to the abuse; and coping resources expected to mediate effects of vulnerability factors and to influence the mobilization (of lack thereof) of coping responses. There were significant differences in coping capacity profiles across the four groups. These appeared to be a continuum of coping capacity, with women who were most directly threatened showing the lowest and women who were least directly threatened showing the highest levels of coping capacity. In order from the lowest to the highest levels of coping capacity were (1) battered women, (2) women whose partners are offenders against their children, (3) women whose partners are offenders against children of whom they are not the parent, and (4) control group women. The paper ends with a conceptual interpretation of the mediating functions of coping resources and implications for intervention and further study.


The role of family factors, physical abuse, and sexual victimization experiences in high-risk youths' alcohol and other drug use and delinquency: a longitudinal model.

Our understanding of the adverse effects of early child physical and sexual abuse has developed to a point where there is need to elucidate the processes by which various developmental outcomes occur. Limited variability on key measures of family stress and in youths' drug use, other delinquent behavior and abuse histories in the general population has limited theory development. Using data from an ongoing, longitudinal study of juvenile detainees, we test a developmental damage model of the relationships among the youths' family background and problem factors, their sexual victimization and physical abuse experiences, and their substance use and delinquent behavior over time. The hypothesized model was supported by the data. Theoretical and policy implications of the results are drawn. In particular, early intervention with high-risk youths and their families is needed to address effectively their problems and troubled behavior before drug use and delinquent careers become firmly established.


After the crisis: a needs assessment of women leaving a domestic violence shelter.

The current study presents the results of a needs assessment of 141 women exiting an emergency shelter for women with abusive partners. Extensive in-person interviews were conducted. Results indicate that battered women need numerous community resources upon their shelter exit, including legal assistance, employment, and housing. Race, age, and whether a woman was returning to her assailant influenced which resources she reported needing at shelter exit. Most of the women had experienced severe abuse and injuries, and required physical protection. Implications of these findings as they relate to program development and integration of social services are discussed.


The role of mitochondrial DNA rearrangements in aging and human diseases.

Instabilities and point mutations of the high molecular weight mitochondrial DNA (mtDNA) were shown to be correlated with various degenerative processes in both lower eukaryotes as well as in mammals. In filamentous fungi, circular and linear plasmids were demonstrated to be involved in mtDNA rearrangements and in the genetic control of senescence. In addition, in these eukaryotic microorganisms, which have proved to be ideal model systems in experimental gerontology, a number of nuclear genes were identified controlling the stability of the mitochondrial genome. Although the mitochondrial genome of mammals, including humans, appears to be quite stable in comparison to other species, mtDNA instabilities of the type described in fungi were observed in mitochondria of patients with different mitochondrial degenerative disorders (CPEO, KSS, Pearson syndrome, LHON, MERRF, MELAS). It was later demonstrated that such mtDNA rearrangements appear to accumulate progressively during aging in human subjects. These data suggest that instabilities of the mitochondrial genome may play an important role in the control of life span not only in lower eukaryotes, but also in humans.


Coping with health problems in old age. A longitudinal approach.

An analysis of medical, psychological, and social data of the Bonn Longitudinal Study on Aging, comparing a subgroup of the BOLSA sample, which developed different forms of chronic disease four to six years after the beginning of the study, and a healthy subsample, points to different patterns of coping in these two subgroups. The sequence of these response patterns provides some evidence for a special form of psychosocial competence of chronically ill aged persons, which developed in an 'accelerated' way in the ill group, and in a retarded way in the initially healthy group. The findings emphasize the need for continuing research into the psychosocial aspects of coping with chronic disease in old age.


The oldest old and their children: how strong are the relationships?

Eighty-five-year-old parents (N = 99) and their middle-aged children (N = 58) participated in a study on solidarity in intergenerational relationships in Sweden. The research model utilized evaluated six dimensions of family solidarity: family structures and associational, affectional, consensual, functional and normative solidarity. The finding of close family bonds in most of these areas may be attributed to the fact that the extensive Swedish public home-help system facilitated relationships on more equal terms. While the children were relieved from much responsibility for their parents' needs, most parents did not experience feelings of dependency on their children. It was in fact evident that even very old parents can be a source for help to their children. Children were, however, the main providers for emotional support and this role could not be substituted by formal caregivers.


Differences in cerebrospinal fluid gangliosides between "probable Alzheimer's disease" and normal aging.

The four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, were determined in cerebrospinal fluid (CSF) of 43 patients with "probable Alzheimer's disease (AD)" and 40 healthy controls without psychiatric or neurological disorders. The total concentration of the four gangliosides did not differ significantly between "probable AD" group (116 +/- 58 nmol/L) and controls (92 +/- 31 nmol/L), but the proportion between the gangliosides was changed. In the "probable AD" group compared with the age-matched control group, there was an increase in both the GM1 (22.6 +/- 9.3% vs 12.6 +/- 4.1%; p < 0.0001) and GD1a (32.1 +/- 9.8% vs 23.3 +/- 5.7%; p < 0.0005) proportion, and a decrease in the GD1b (20.0 +/- 6.6% vs 23.8 +/- 6.0%; p < 0.05) and GT1b (25.3 +/- 7.9 vs 40.3 +/- 9.3%; p < 0.0001) proportion. The proportion of GM1 showed a positive correlation with age in the control group (r = 0.45; p < 0.01), but a negative correlation with age in the "probable AD" group (r = -0.37; p < 0.05). Thus, although the increase in proportion GM1 in the "probable AD" group was preferentially found in younger "probable AD" patients, it was not caused by age differences. While the pathogenetic mechanism for these changes in CSF-gangliosides in "probable AD" remains to be established, it may reflect the degeneration of nerve cells and synapses.


Components of competence in the community aged.

Following a discussion of different approaches to the definition of 'competence' and their theoretical background, the need for both situation-specific and global conceptualizations of this construct is stressed. Aside from competencies for physical and social survival, those related to psychological survival should be considered. A battery of indicators of competence, as used in the Bonn Longitudinal Study on Aging (BOLSA), was helpful in identifying six groups of elderly people with different levels of competence in the range of 'normal' aging. Cognitive and personality variables most significantly differentiated the competence groups. On the basis of these findings, the value of complex competence models and the need for situation-specific and person-specific assessments of competence is stressed.


Unrecognized dementia: sociodemographic correlates.

Eighteen geriatric patients, aged 77 +/- 8 years, in whom a diagnosis of dementia was formulated during an unrelated hospital stay, were studied to clarify why dementia had not been detected at an earlier stage. The control group was composed of 20 patients aged 79 +/- 11 years with a comparable degree of cognitive impairment who had been recognized 1-3 years previously. The index group was characterized by a lower formal education (5.2 +/- 3.7 years vs 8.5 +/- 4.7 years, p < 0.05), and higher prevalence of subjects living in rural areas (50% vs 10%, p < 0.006); other sociodemographic variables (age, sex, marital status, employment before retirement) could not distinguish the groups. A multivariate logistic regression analysis showed that the end point late diagnosis was significantly correlated with the independent variables, rural residence (odds ratio = 4.65, C.I. = 1.7-12.9) and lower occupational role (odds ratio = 3.3, C.I. = 1.2-9.5). A structured interview with relatives of the patients disclosed 3 main reasons accounting for later diagnosis: poor awareness of the problem of dementia; respect for parents and grandparents; and negligible effect of this problem on family life and economy. In the control group, dementia had been diagnosed earlier mostly because of its heavier social and economic impact on the family.


Differentiated thyroid carcinoma in the elderly.

Prognostic factors and therapeutic results in a group of 268 patients with differentiated thyroid cancer (DTC) aged over 60 years are reported. These cases were selected from a total of 1457 DTC-patients seen at our Center from 1967 to 1987. All elderly patients underwent total thyroidectomy, and were treated with 131I therapy and suppressive hormonal therapy. Moreover, external radiotherapy was performed in 20% and chemotherapy in 3.8% of all cases. Follow-up included periodical clinical examination, serum Thyroglobulin (Tg) determination, 131I total body scan (TBS), and echographic and radiologic survey. Several unfavorable prognostic factors were identified in elderly patients with DTC. In comparison with data obtained in a group of patients under 60 years of age, 1) the follicular histologic type was increased, papillary/follicular ratio was 1.1 vs 2.6; 2) the F/M ratio was decreased, 1.5 vs 2.8 for papillary tumors, and 1.7 vs 3.6 for follicular tumors; 3) the rate of cases with local extrathyroid tumor growth and distant metastases was higher, and 4) rates of metastases to bone and metastases with low 131I uptake were increased. Moreover, the 10-year survival rate in elderly patients with lymph node and distant metastases was significantly reduced compared to younger patients, both for papillary and follicular cancer. The finding of detectable serum Tg levels was well correlated with the presence of metastatic disease. Moreover, Tg sensitivity was higher than TBS in showing the presence of metastatic foci. DTC in elderly people must be considered an aggressive tumor both for follicular and papillary histologic types. A radical approach is recommended: total thyroidectomy, 131I administration, and suppressive hormonal therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


80-year-old men have elevated plasma concentrations of catecholamines but decreased plasma renin activity and aldosterone as compared to young men.

Plasma concentrations of adrenaline, noradrenaline, aldosterone and plasma renin activity were determined in a selected group of 80-year-old men (N = 41) in good health without clinical signs of cardiovascular disease, and were compared to levels in young healthy males (N = 20, 24-28 years). Plasma adrenaline and noradrenaline concentrations were higher (0.24 median; 25th-75th percentiles 0.16-0.34 nmol/L vs 0.15; 0.11-0.18 nmol/L, p < 0.01 and 2.22; 1.58-3.27 nmol/L vs 1.15; 1.00-1.74 nmol/L, p < 0.001), and plasma renin activity and plasma aldosterone concentration were lower in the old than in the young men (0.65; 0.35-1.04 micrograms/L/1h vs 2.09; 1.23-2.41 micrograms/L/1h, p < 0.001 and 0.12; 0.09-0.19 nmol/L vs 0.38; 0.28-0.54 nmol/L, p < 0.001). In conclusion, increased plasma concentrations of catecholamines and decreased plasma concentration of aldosterone and plasma renin activity in old men, as compared to young men, must be considered when interpreting data of these hormones in elderly men.


A comparison of community care of elderly people in Wales and Northern Ireland.

This study compares the provision of community services for elderly people in Wales and Northern Ireland using data from two independent surveys. Despite sampling and definitional problems, certain interesting comparisons can be obtained. In general, elderly people in the Northern Ireland sample seem more likely to be dependent and more disabled than those in Wales. Northern Ireland people receive less help, but the help given is more likely to be from statutory services than in Wales; in many cases statutory help is the sole source of support. Further, in Wales there is more specialized care for very disabled elderly people living in the community, and the work is more likely to be shared by carers and the statutory services. There is however still considerable unmet need in both countries. A comparative study using common definitions and methods would be of considerable interest in relation to the debate concerning the relative shares of health care resources in the United Kingdom.


[Molecular and cellular aspects of the cardioprotective mechanism of phosphocreatine].

The present state of investigations on molecular and cellular mechanisms of cardioprotective effects of phosphocreatine (PCr) is reviewed. The protective effect of PCr is manifested as significant improvement of heart contractile function recovery, lowering of diastolic pressure elevation and myocardial enzymes release during postischemic reperfusion as well as better preservation of high energy phosphates in comparison with control. Data from multidisciplinary studies using physico-chemical, physiological, pharmacological etc. approaches suggest that one of the key mechanisms of PCr action is its interaction with the sarcolemmal membrane. The authors own data obtained with the use of spin-labeled ESR-probe incorporated into the isolated sarcolemmal vesicles provide direct evidence in favor of the ordering effect of PCr sarcolemmal phospholipid packing with essential involvement of Ca2+ ions. PCr transform membrane phospholipids into more structured gel-like state. The results of biomedical studies suggest that the mechanism of this protective action is complex and includes at least four components: 1) inhibition of lysophosphoglyceride accumulation in the ischemic myocardium and preservation of cardiac cell sarcolemma structure via zwitterionic interaction with PCr molecules; ii) extracellular action consisting in inhibition of platelet aggregation via ADP removal in the extracellular creatine kinase reaction and increasing plasticity of red blood cells; iii) PCr penetration into cells maintenance of high local ATP levels is possible; iiii) inhibition of adenine nucleotide degradation at the step of 5'-nucleotidase reaction in cardiac cell sarcolemma.


[Enzymes in thick filaments of vertebrate cross-striated muscles].

Contemporary data on three enzymes of vertebrate cross-striated muscle thick filaments, such as creatine kinase, AMP-deaminase and phosphofructokinase, are reviewed. The physico-chemical, enzymatic and regulatory properties and localization of these enzymes in different zones of the thick filament are considered. The functional relevance of localization of creatine kinase, AMP-deaminase and phosphofructokinase on thick filaments is discussed in terms of the possible role of the enzyme adsorption on subcellular structures in regulation of metabolic processes.


[The effect of lysolecithin on rat liver microsome monooxygenase activity after induction by xenobiotics of the methylcholanthrene type].

Effects of exogenous gamma-myristoyl- and gamma-palmitoyllysolecithins on physico-chemical characteristics of rat liver microsomes, such as hydrophobicity and viscosity, as well as on oxidative NADPH-dependent O-deethylation of 7-ethoxycoumarin (7-EC), O-demethylation of p-nitroanisole (p-NA) and hydroxylation of 3.4-benz(a)pyrene (BP) induced by the mechylcholanthrene xenobiotics methylcholanthrene (MCh), beta-naphthoflavone (NF) and Sovol (SV) have been investigated. The specific inducible form of P-450c showed different affinity for the substrates. Lysolecithin decreased the hydrophobicity but only slightly increased membrane viscosity, whereas the monooxygenase substrates neutralized these effects. Lysolecithin (2-20 micrograms/mg of microsomal protein) inhibited the activity of deethylase 7-EC (maximally by 11%) in NF- and SV-induced microsomes, this inhibiting effect being more pronounced than that in MCh-induced microsomes. At higher concentrations lysolecithin inhibited the rate of 7-EC deethylation in MCh-induced microsomes more strongly; the maximal inhibition (23%) was observed at the protein concentration of 60 micrograms/mg. In case of NF- and SV-induced microsomes the inhibition was 18%. The inhibiting effect of lysolecithin on 7-EC dealkylation was expressed in a lesser degree than that on p-NA O-demethylation in induced (but not intact) microsomes. A significant positive correlation has been found between the changes in hydrophobicity and inhibition rates in the presence of lysolecithin, however only for 7-EC deethylation.


[Regulation of the activity of neuron-specific enolase by certain endogenous compounds].

The effects of glycolysis metabolites and some amino acids on the activity of bovine brain enolase have been studied. The inhibiting effect of glycolysis metabolites, of which two (2-phosphoglycolate and glyceraldehyde 3-phosphate) may be functionally significant, has been demonstrated. The action mechanisms of these compounds within a range of physiological concentrations as well as the combined effect of glyceraldehyde 3-phosphate and phosphoglyceromutase on enolase activity have been investigated.


[The effect of tetrahydrofuran on the microsomal monooxygenase system in vitro and in vivo].

The effects of tetrahydrofuran (THF) on rat liver microsomes in vitro and in vivo were opposite. In vitro THF inhibited the p-nitrophenol (PNP) hydroxylase activity of microsomes from control rats and from rats treated with PB, acetone, and isoniazide--by 50, 20, 60, and 80%, respectively. THF inhibited dimethylnitrosamine (NDMA) demethylation in control and induced microsomes in a lesser degree. THF increased the total cytochrome P-450 content as well as the contents of cytochromes P-450IIE1 and P-450IIB1/B2. The activities of PNP-hydroxylation and NDMA-demethylation increased also, whereas the PR-dealkylation activity was unchanged. An increase in the THF dose caused inhibition of the rat liver microsomal monooxygenase system.


[Uneven distribution of amino acid substitutions throughout the amino acid sequence of homologous proteins].

A set of aligned homologous protein sequences is divided into two groups consisting of m and n most related sequences. The value of position variability for homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible m*n pairs of amino acid residues in that position divided by m*n. The position variability value plotted versus the sequence position number with a window of 10 positions gives the intergroup local variability profile. Area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area Sr for 1000 random homologous protein families. If S is greater than Sr by more than 2 standard deviation units sigma r, the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(Sr+ 2 sigma r) are cut off by two straight lines to locate significant regions. The difference (S-Sr) given in standard deviation units sigma r is believed to be the amino acid substitution overall irregularity along the homologous protein sequences OI = (S-Sr)/sigma r. The significant conservative and variable regions of six homologous sequence families (phospholipase A2, cytochromes b, alpha-subunits of Na,K-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre and human rhodopsins) were identified. It was shown that for artificial homologous protein sequences derived by k-fold lengthening of natural protein sequences, the OI value rises as square root of k. To compare the degree of substitution irregularity in homologous protein sequence families of different lengths L the value of standard substitution overall irregularity for L = 250 is proposed.


[Purification and properties of pyrocatechase II from Pseudomonas putida strain 87].

Induction of modified ortho-pathway enzymes (catechol 1.2-dioxygenase II, muconate cycloisomerase II, dienelactone hydrolase, and maleylacetate reductase) was found in Pseudomonas putida 87, when 3-chlorobenzoic acid was used as a sole carbon and energy source. Catechol 1.2-dioxygenase II, the key chlorocatechol cleaving enzyme, was purified and characterized. The enzyme molecular mass as determined by gel filtration was 65,000 Da; the minimum molecular mass upon SDS electrophoresis was 33,000 Da. The pH and temperature optima for the enzyme were 7.2-7.8 and 35 degrees C, respectively. The highest stability of catechol 1.2-dioxygenase II upon storage was observed in 50 mM Tris-HCl buffer pH 7.8 at 4 degrees C. The relative values of Vmax for catechol 1.2-dioxygenase II with 3-chloro-, 4-chloro-, and 3.5-dichlorocatechols were 28%, 50%, and 41% of those for catechol. The enzyme affinity for chlorocatechols was 3-9 times higher than for methylcatechols and 10-20 times higher than for unsubstituted catechol.


[Isolation and properties of superoxide dismutase from human blood plasma].

A procedure for purification of superoxide dismutase (SOD) from human blood plasma has been developed, which includes gel filtration on Ultrogels AcA-34 and AcA-44 (LKB, Sweden). The protein purified from blood plasma is a glycoprotein which is thermostable at 70-80 degrees C. The molecular mass of the protein determined immediately after gel filtration is approximately 147,000 daltons. A comparative analysis of effects on the SOD activity of plasma and erythrocytes of compounds capable of forming chelating complexes with metals within the enzyme active center has been carried out. The purified enzyme differs by its physico-chemical characteristics from cytosolic Cu,Zn-SOD and pertains to a new class of SOD, the so-called extracellular SOD, detected in some biological fluids.


[Energy metabolism and contractile function of the heart in diabetic cardiomyopathy: effect of ischemia and reperfusion].

Physiological parameters, rates of mitochondrial respiration, high energy phosphate levels and creatine phosphokinase (CPK) activity were investigated in the hearts from control and alloxan-induced diabetic rabbits before and after 40-min total ischemia and reperfusion. Diabetic hearts demonstrated significant decreases in the rates of contraction (+dP/dt) and relaxation (-dP/dt), heart rates and cardiac work compared to control hearts. Determination of mitochondrial respiration rates in saponin-skinned fibers showed a low mitochondrial respiratory function in diabetic hearts. It was found that the ATP and ADP levels and the total and mitochondrial isoenzyme activities of CPK in diabetic hearts were lowered in comparison with control. A post-ischemic recovery of cardiac performance for diabetic hearts was better than in controls. After reperfusion diabetic hearts had increased ATP levels. The data obtained demonstrate some abnormalities of both cardiac performance and energy metabolism in the hearts of diabetic animals and a decreased sensitivity of the latter to ischemic injury.


Studies on gastroprotection induced by capsaicin and papaverine.

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose-dependently the area of ethanol-induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i.v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i.v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.


Direct protective action of epidermal growth factor on isolated gastric mucosal surface epithelial cells.

Epidermal growth factor (EGF) protects gastric mucosa against acute injury produced by a variety of damaging agents, but the mechanism of its protective action is not clear. Since the surface epithelial cells (SEC) are important component of gastric mucosal defence, we studied whether EGF may directly protect isolated gastric SEC against ethanol injury in vitro, in condition independent of systemic factors and whether endogenous prostaglandins may play a role in EGF's protective action. The isolated SEC from rat gastric mucosa were preincubated in medium only, or medium containing 0.0001-10.0 micrograms/ml of h-rEGF for 15 minutes, and incubated with 8% ethanol for 1 hour. In another study the above experiment was repeated but cells were pretreated with 10(-4) or 10(-5) M indomethacin before EGF treatment. The cell viability was assessed by fast green exclusion test. Incubation of SEC with 8% ethanol significantly reduced SEC cell viability to 50 +/- 2%: EGF 0.1 or 1.0 microgram/ml significantly reduced ethanol induced damage (cell viability 59 +/- 3 and 62 +/- 3% respectively). Pretreatment with 10(-4) M indomethacin (the dose which does not affect SEC viability but inhibit PGE2 and PGI2 generation), significantly reduced protective action of EGF against 8% ethanol injury. EGF 1.0 and 10.0 micrograms/ml alone without ethanol increased PGE2 and 6 keto PGF1 alpha generation by SEC. These studies demonstrated: 1) EGF is able to protect gastric surface epithelial cells directly without mediation by systemic factors. 2) EGF induced protection of SEC may in part be mediated by prostaglandins.


Platelet activating factor (PAF) inhibitor (TCV-309) reduces caerulein- and PAF-induced pancreatitis. A morphologic and functional study in the rat.

Caerulein-induced acute pancreatitis was studied in rats. Consistent with this type of acute pancreatitis morphological (edema, leukocytic infiltration and acinar cell vaculization) and biochemical (increase in pancreatic protein content. PAF release and serum amylase) changes developed 5 hours after caerulein administration. In addition increase in pancreatic weight and decrease in pancreatic blood flow were noticed. PAF administration caused pancreatic damage similar in some parameters to caerulein-induced pancreatitis, along with reduction of pancreatic blood flow, increase in pancreatic protein content, and serum amylase. TCV-309, a selective PAF antagonist, administered prior to caerulein and/or PAF, reduced caerulein-induced pancreatitis and prevented PAF-induced pancreatitis. Results of our present studies indicate the crucial role of PAF in pathogenesis of experimental acute pancreatitis.


The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart.

The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.


Vasopressin release from posterior pituitary lobe incubated in situ after preganglionic stimulation of the rat superior cervical ganglion.

In urethane-chloralose anaesthesia the pituitary gland was exposed by transpharyngeal approach in rats. The anterior lobe was removed and the posterior lobe was incubated in situ, that is in conditions of anatomical integrity of the hypothalamus with the posterior pituitary lobe. The 15-min samples of the medium incubating the posterior pituitary lobe in situ were collected. Vasopressin (AVP) content in the incubation medium was determined by radioimmunoassay. The stimulation of preganglionic fibers of the superior cervical ganglion (SCG) with alternate short (5 s) bursts of electric pulses with short (5 s) breaks did not change AVP release. However, stimulation of preganglionic fibres with alternate long (30 s) bursts of electric pulses with long (30 s) breaks evoked an increase in AVP release after some latency. Probably, at the hypothalamic or posterior pituitary level temporal summation should occur affecting vasopressinergic neurons or their endings and evoking AVP release.


Induction of ornithine decarboxylase in normal and protein kinase C--depleted human colon carcinoma cells.

To examine the role of protein kinase C (PKC) in induction of human colon adenocarcinoma cell line, DETA/W, by polypeptide growth-promoting factors, ornithine decarboxylase activity (ODC) and DNA synthesis were determined in cells depleted of PKC. PKC depletion was achieved by prolonged cultivation (more than 30 passages) with 10(-6) M phorbol 12-myristate 13-acelate. Lack of PKC in studied cells was proved by measurements of PKC activity and immunoreactivity. Although ODC activities and DNA syntheses in PKC-depleted cells were decreased by about 40-50% compared to normal DETA/W cells, the percentage increase of these mitogen-responsive reactions was quantitatively similar in both cell sublines. These results raise the possibility that not all of the biological responses to growth factors are connected with the activation of calcium-dependent PKC.


Human centrifugation: new approach in the treatment of diabetic background retinopathy (preliminary communication).

In previous studies we reported that Human Centrifugation Treatment (HCT) provoked endogenous prostaglandin liberation by a mechanical stimulus over the vessel walls. Up to now, the importance of Prostacyclin (PGI2) and HCT in the treatment of diabetic retinopathy has not been investigated. We studied the efficacy of one month of HCT in background retinopathy (BR). We evaluated the evolution of the visual acuity and the eye fundus at one, three six and one year after HCT in twenty-five patients. PGI2 levels were determined before and after HCT in seven patients and four normal volunteers. HCT was performed in a centrifuge Isasi's Model. Patients were exposed daily for 1 hour to acceleration profiles from head to feet during a period of a month. This preliminary communication demonstrated that: HCT provokes endogenous PGI2 liberation (p < 0.001), b) HCT substantially reduces vascular leakage and macular edema improving the visual acuity (p < 0.001); c) HCT has long-lasting beneficial effects.


In vitro uptake of 18-hydroxycorticosterone by regions of the central nervous system.

The specific uptake of tritiated 18-hydroxycorticosterone (18-OH-B) by purified cell nuclear fractions and cytosol of medulla oblongata, pons, amygdala, anterior pituitary, hypothalamus, hippocampus, preoptic-area and lung from adrenalectomized animals was investigated after incubation of tissue sections with radioactive ligand. We found that 18-OH-B was taken up mainly by nuclei obtained from pons and medulla oblongata; this profile differs from previous observations with the closely related steroids corticosterone and aldosterone, which are mostly concentrated by the limbic system. Based on this finding, as well as on former studies with 18-OH-B, we suggest that this steroid may exert its action on renal excretion of protons as well as on central nervous system structures involved in respiratory regulation, related to that excretion.


Time-dependency for the effect of different stressors on rat pineal melatonin content.

This study describes the effects of two stressors, swimming for 15 min or i.p. beta-carboline (beta-CCE) injection, on rat pineal melatonin levels when applied either at the end of the light period of daily photoperiod (1800 h) or at the expected melatonin maximum (at 2200 h). Neither procedure affected melatonin levels at 1800 h. In contrast, both stressors were effective to augment pineal melatonin content when applied at 2200 h. When applied at light-dark transition, only beta-CCE injection increased pineal melatonin levels at the middle of the night. Neither procedure was effective to counteract the inhibition of pineal melatonin content caused by prolonging the light phase for 4 h. Deprivation for two days of water, but not of food, augmented pineal melatonin levels in rats killed at the end of the light period, up to levels that were undistinguishable from those found at 2200 h. No differences were found between the two stressors and controls when tested at 2200 h. The present results further support the concept that stressful stimuli can influence differentially pineal melatonin production.


[Evaluation of the method for early pregnancy factor detection (EPF) in swine. Significance in early pregnancy diagnosis].

Early pregnancy factor (EPF) is a protein detected in the serum of pregnant females in most mammals, before implantation of the embryo; its activity is detected by the rosette inhibition test (RIT). After preincubation of lymphocytes in serum of non-pregnant pigs, the mean titre of RIT was 10.80 +/- 0.32. The upper limit of the 95% confidence interval was calculated to be 11.44. Therefore, all titres 12 were defined indicating the presence of EPF activity. The incubation of lymphocytes in serum of pregnancy caused a significant increase in the mean rosette inhibition titre, raising it to 19.88 +/- 1.13 (p < 0.001). False negative results were obtained for 10% of pregnant pigs. EPF positive activity was detected in only one non-pregnant pig (RIT = 20). This assay is not quantitative nor suitable for pregnancy diagnosis taking into account RIT values dispersion.


Human centrifugation machine a physiological stimulator of endogenous prostaglandin synthesis.

A new model of human centrifugation machine with clinical purposes which makes possible to stimulate endogenous prostaglandin synthesis by a mechanical stimulus over the vessel walls is presented. The different therapeutical applications of this machine were demonstrated in lymphedema, peripheral obstructive arteriopathies, reflex sympathetic dystrophy syndrome, diabetic background retinopathy and coronary artery disease.


The effect of parental alcohol dependence on perceived children's behavior.

The effect of past-year parental alcohol dependence on perceived children's behavioral problems was assessed using data from a general population sample of 3,409 father-child pairs and 5,892 mother-child pairs. Eight percent of the children living in households containing fathers had an alcoholic father; 2% of those living with mothers had an alcoholic mother. Behavioral problems in the 3 months preceding the interview were assessed using a list of 32 indicators and were evaluated by an adult household member, usually the child's mother. The unadjusted odds of a child's being in the top 10th percentile of the behavioral problem distribution were increased by a factor of 1.7 for paternal alcoholism and 2.2 for maternal alcoholism. After adjustment for social and demographic characteristics of the child and family, the odds ratio for alcohol dependence in the mother dropped to 1.6; the odds ratio for paternal alcohol dependence remained at 1.7. Parental alcohol dependence did not interact with social and demographic factors in its association with children's behavioral problems.


The relationship of dieting severity and bulimic behaviors to alcohol and other drug use in young women.

Patients with bulimia nervosa frequently have problems with alcoholism and other substance abuse. The goal of this study was to assess whether this relationship between eating abnormalities and substance abuse extends to subthreshold levels of dieting and substance use. A self-administered questionnaire assessing dieting and substance use (alcohol, cigarettes, and marijuana) was completed by 1,796 women prior to their freshman year in college. Using a scale derived from DSM-III-R criteria for bulimia nervosa and previous research in this population, subjects were categorized as nondieters, casual, intense, severe, at-risk or bulimic dieters. The relationship between the dieting-severity category and frequency and intensity of alcohol use and frequency of marijuana and cigarette use was assessed. DSM-III-R criteria for bulimia nervosa were met by 1.6% of the women. Only 13.8% of these women were nondieters. Increasing dieting severity was positively associated with increasing prevalence of alcohol, cigarette, and marijuana use and with increasing frequency and intensity of alcohol use. The bulimic and at-risk dieters were similar in their alcohol and drug use. The relationship between eating disorders and alcoholism and other substance abuse noted in clinical populations extends in a continuous, graded manner to subthreshold levels of dieting and substance use behaviors. Dieting-related attitudes and behaviors in young women may be related to increased susceptibility to alcohol and drug abuse.


The development and reliability of the RAATE-CE.

The Recovery Attitude And Treatment Evaluator-Clinical Evaluation (RAATE-CE) utilizes a brief, structured clinical interview that assesses five key dimensions that produce a clinically relevant and useful severity profile of the patient for making placement, continued stay, discharge, and treatment-planning decisions. The RAATE-CE also measures treatment progress. These five dimensions are: (A) degree of resistance to treatment (including denial of addiction problems); (B) degree of resistance to continuing care (including self-help groups); (C) acuity of biomedical problems; (D) acuity of psychiatric-psychological problems; and (E) the degree to which the psychosocial environment is supportive or detrimental to recovery. Data on 139 publicly funded, high-severity subjects suggest that the RAATE-CE demonstrates an interrater reliability across the five dimensions between .59 and .77, and an internal consistency reliability range between .65 and .87.


Alcohol and anxiety: postdrink-performance feedback alters affective and self-evaluative responses to a subsequent social stressor.

Several models of alcohol use and abuse implicate self-evaluation as a variable that mediates alcohol's anxiolytic effects. Self-evaluation when drinking, in turn, is affected by people's causal attributions for their behavior and alcohol expectancies. Accordingly, postdrink performance feedback was manipulated by having 20 subjects engage in a set of tasks before and after a moderate dose of alcohol. Half of the subjects received feedback that alcohol impaired their task performance whereas the other half received feedback that alcohol did not impair their performance. All subjects then participated in a stressful social interaction. As expected, subjects in the high behavioral impairment condition made more external performance attributions during the social stressor and reported less negative self-evaluation and subjective anxiety than subjects in the low behavioral impairment condition. Alcohol expectancies appeared to account partially for the data. The results indicate that information concerning alcohol-induced behavioral impairment moderates alcohol's effects on self-evaluation and subjective anxiety.


A Cocaine High-Risk Situations Questionnaire: development and psychometric properties.

Although high-risk situations have been identified for alcoholism, opiate abuse, and smoking, further research is needed to identify high-risk situations for cocaine abuse. A 233-item Cocaine High-Risk Situations Survey was developed based on a comprehensive literature review and was administered to 179 cocaine users in treatment. Situations that occurred infrequently or that were not often associated with cocaine use were eliminated and the remaining 89 items were factor analyzed using half the sample with confirmatory factor analysis on the remainder of the sample. Only one factor was found for frequency of cocaine use in these situations. The 21 items with high factor loadings and a diverse range of content were retained for subsequent analyses and renamed the Cocaine High-Risk Situations Questionnaire (CHRSQ). Reliability and convergent and discriminant validity of this scale were demonstrated. Frequency of alcohol use in the same situations was not significantly related to cocaine use and abuse, supporting discriminant validity. The findings suggest that the frequency of ongoing cocaine use is not determined by specific situations. Theoretical and clinical implications are discussed.


Alcohol use and personality relationships in U.S. and Polish adolescents.

To obtain information, which could be useful to the design of intervention and prevention programs for adolescent alcohol users and potential users, personality and alcohol use data were collected from over 300 Polish and U.S. 15-year-olds. Thirty percent of these subjects were already drinking on a more or less consistent basis. Users were angry, nonconforming, and impulsive-antisocial persons in both countries. Future research and potential intervention and prevention strategies are discussed.


Observer reports of smoking status: a replication.

Observer and self-reports of abstinence from smoking were compared at 2-, 7-, 14-, 30-, 90-, and 180-day follow-ups and with biochemical verification at 180-day follow-up in a study of 630 self-quitters. Observer reports were often not returned (25-65%), rarely refuted self-reported abstinence (< 1%), and were often discordant with biochemical results (32%). These results replicate a prior finding (Hughes, 1990) that observer verification of smoking status during a prospective study of cessation is not very helpful.


Basic fibroblast growth factor high and low affinity binding sites in developing mouse brain, hippocampus and cerebellum.

Fibroblast growth factors (FGFs), first extracted from brain and retina, are potent neurotrophic factors. They stimulate neuroblast proliferation and neuron differentiation and survival. In order to study the spatial and temporal distribution of the target cells in the mouse brain we studied by autoradiography and quantified by image analysis 125I-bFGF binding sites as a function of development. We have revealed the presence of two types of specific bFGF receptors. One is heparitinase sensitive and is co-localized with heparan sulfate proteoglycans of the basement membranes (meninges, choroid plexus and blood vessels). It is not developmentally regulated and corresponds to the low affinity receptors. It may be a storage form. The second type is heparitinase resistant and is modified during development, matching, in the adult, layering of the hippocampus and cerebellum. At 13 days of embryonic development there is a preferential distribution of silver grains on the ecto- and neuroectodermal tissues. In the adult, the labeling is localized on the neural process layers. It likely corresponds to the specific binding to cell high affinity receptors. Binding patterns according to the developmental stages of the brain can be correlated with mitotic, migration and differentiation phases of the neuronal cells.


The role of calcium, polyamines and centrosomes in the formation and organization of cleavage furrows in amphibian eggs.

Cleavage furrows of amphibian eggs exhibit characteristic morphological features: the presence of finger-like microvilli (MV) along their outer edges, the formation of furrow walls from new plasma membrane lacking MV, and the subsequent retrieval of this membrane during the infolding of the furrow. A similar structure can be induced, specifically, by certain cytoplasmic components such as centrosomes, polyamines and calcium. Their respective roles in the events associated with the furrowing process have been investigated by injecting these agents into nucleated and enucleated Pleurodeles eggs and evaluating their effects using cytochemical labelling of the egg surface with a biotin-streptavidin system. The injection of polyamines (spermine or spermidine) and in some cases, calcium into enucleated eggs provoked MV elongation and the appearance of newly formed, smooth plasma membrane. In these eggs, this membrane was not incorporated into the furrows, and as a consequence, the blastomeres did not actually separate. In contrast, the injection of centrosomes into enucleated eggs induced both the incorporation and internalization of new membrane, resulting in the formation of furrows and a true cellularization of the eggs, identical to the cleavage process observed in fertilized eggs. The present results provide further evidence that the establishment of the furrow depends on two complementary interacting systems: the contractile elements of the egg cortex which regulate the insertion of new membrane and the mitotic center which is essential for the invagination of the furrow.


Structure of the mouse gene encoding peripherin: a neuronal intermediate filament protein.

The gene encoding mouse peripherin, a neuronal intermediate filament protein, has been cloned. Its sequence, through 1021 nucleotides composing the 5'-flanking region, nine exons, eight introns and 547 nucleotides of the 3'-flanking region, as well as its transcription initiation site have been determined. The amino acid coding sequence differs from that of the rat peripherin gene. The mouse gene has an additional histidine near the N-terminal end, and shows three conservative and two non-conservative changes. The promoter sequence, containing the binding sites for transcription factors as well as other sequences is homologous to promoter regions of other type III intermediate filament protein genes and other neuronal-specific genes.


Changes in retinal pigment epithelial cell autofluorescence and protein expression associated with phagocytosis of rod outer segments in vitro.

The accumulation of autofluorescent lipofuscin was quantified in cultured human retinal pigment epithelial (RPE) cells phagocytosing bovine rod outer segments (BROS) and the expression of proteins in these cells was investigated. Results showed a steady increase in autofluorescence of RPE cells over a 4-week period as measured by fluorophotometric flow cytometry. A significantly greater increase in autofluorescence was found in the cultured RPE cells from a 7-year-old donor compared with those from a 47-year-old donor. Within both groups the BROS-challenged cells had significantly higher fluorescence readings than the control cells which were not challenged. Autoradiography of 35S-labelled proteins separated by polyacrylamide gel electrophoresis (PAGE) revealed a small distinct band at 102 kDa in BROS-challenged RPE cells of both bovine and human origin that did not appear in control or microsphere-phagocytosing RPE cells. The intensity of the signal was unrelated to the duration of the challenge period.


Principal and intercalated cells in primary cultures of rabbit renal collecting tubules revealed by monoclonal antibodies.

In this study we describe the production and characterization of two monoclonal antibodies (mAb 503 and mAb 703) raised against the apical membrane of rabbit cortical collecting tubule (CCT) cells. The specificity of the two monoclonal antibodies was studied by immunoelectron microscopy on kidney sections. These antibodies were used to identify principal and intercalated cells in primary cultures of CCT. To assess the maintenance of the basic characteristics of the cortical collecting cells during the growth process we determined the biochemical and electrophysiological properties of cultured CCT. Of the monoclonal antibodies produced mAb 503 was specifically directed against the luminal membrane of intercalated cells as shown by immunoelectron microscopy. mAb 703 bound specifically the apical membrane of the principal cells. In primary cultures of CCT mAb 503 and mAb 703 bound antigens present on the apical membrane of different cells and permitted the study of the distribution of the two cell types. Results showed the maintenance of the epithelial polarity of cultured CCT and the expression of specific antigens.


D-galacturonic acid derivatives as acceptors and donors in glycosylation reactions.

Jones oxidation of suitably protected allyl beta-D-galactopyranosides and subsequent esterification were reinvestigated. Partial deprotection of the resulting D-galacturonic acid derivatives afforded compounds suitable for transformation into glycosyl acceptors. The synthesis of 2-, 3-, and 4-trityl ethers, relying on efficient differential protecting-group strategies, is described. Trityl-cyanoethylidene condensation of these trityl ethers, leading to the protected disaccharide units beta-D-GalpA-(1-->2)-D-GalpA and beta-D-GalpA-(1-->3)-GalpA with high stereoselectivity, is demonstrated. A beta-D-GalpA-(1-->4)-D-GalpA disaccharide was also prepared.


Synthesis of a heteroglycuronan derivative containing the beta-D-galactopyranosyluronic acid (1-->3)-L-rhamnose repeating unit.

Helferich glycosylation of the cyanoethylidene L-rhamnose derivative 3 with the galactosyluronic bromide 2 gave the disaccharide 4 as a key intermediate in the synthesis of the monomer 13 for trityl-cyanoethylidene condensation (TCC). The following formation of the monomer 13, including introduction of a trityl group at O-3', proceeded in six steps. Because of the difficulty of some steps, an alternative route for 13 was tested. Model compounds 20, 21, and 22 were synthesized in order to confirm the stereoregularity of the products of the polycondensation. The polycondensation of the monomer gave D-GalpA-(1-->3)-L-Rha-oligomer derivatives consisting mainly of three repeating units. This result is in contrast with the degree of polymerisation (dp > or = 22) of other synthetic rhamnans, but is very similar to dp 2-7 of homo- and hetero-glucuronan derivatives.


Strong competitive inhibition of porcine pancreatic alpha-amylase by aminodeoxy derivatives of maltose and maltotriose.

The syntheses are described of 6-amino-6-deoxymaltose (2), the 6-amino-6-deoxy (4), 6'-amino-6'-deoxy (6), and 6"-amino-6"-deoxy (8) derivatives of maltotriose, and the methyl alpha- (10) and beta-glycoside (12) and the 1-deoxy derivative (16) of 4. The Ki values (microM) of these competitive inhibitors of porcine pancreatic alpha-amylase were: 2, 88; 4, 1.9; 6, 2.0; 8, 175; 10, 360; 12, 9000; 16, 7600 (cf. 1800 for maltotriose and 3000 for methyl alpha-maltotrioside). The low values for 4 and 6 reflect reinforcement of the normal binding by ionic attraction and, possibly, interaction of the reducing end groups with the protein.


Synthesis of (+)- and (-)-nojirimycin and their 1-deoxy derivatives from myo-inositol.

The conversion of the naturally abundant cyclitol, myo-inositol (4), into (+)-nojirimycin (1a), its enantiomer (1b), and their 1-deoxy analogues (2a and 2b) is described. Biological assay of 2a, 2b, and the bisulfite adducts of 1a and 1b (3a and 3b) showed that the compounds having the unnatural L-gluco configuration (2b and 3b) possess moderate-to-high inhibitory activity against almond beta-D-glucosidase and bovine liver beta-D-galactosidase.


Crystal structure of methyl 3-O-beta-D-glucopyranosyl-beta-D-glucopyranoside (methyl beta-D-laminarabioside) monohydrate.

Crystals of methyl 3-O-beta-D-glucopyranosyl-beta-D-glucopyranoside (methyl beta-D-laminarabioside) belong to the orthorhombic system, space group P2(1)2(1)2, with a = 14.548(2), b = 24.252(7), c = 4.938(1) A, and Z = 4. The crystal structure was solved by the direct method and refined by the full-matrix least-squares procedure to an R-value of 0.062 for 1099 observed reflections in the X-ray data. The molecular structure is similar to that of beta-D-laminarabiose. The torsional angles around the glycosidic bonds are influenced by both the existence of an intramolecular hydrogen bond at O-4'... O-5 and the exo-anomeric effect. In the nonreducing residue, the exocyclic O-5-C-5-C-6-O-6 and C-4-C-5-C-6-O-6 torsional angles are (+)gauche and trans, respectively, whereas the corresponding torsional angles in the reducing residue are (-)gauche and (+)gauche. One water molecule cocrystallizes with each disaccharide, and the crystal structure is stabilized mainly by intra- and inter-molecular hydrogen bonds involving water molecules.


Synthesis and 13C NMR spectra of 2,3-di-O-glycosyl derivatives of methyl alpha-L-rhamnopyranoside and methyl alpha-D-mannopyranoside.

The syntheses are described of 2,3-di-O-glycosyl derivatives of methyl alpha-L-rhamnopyranoside (1-5) and alpha-D-mannopyranoside (6-9). [formula: see text] [table: see text] The deviation from additivity in 13C NMR spectra calculated for 1-9 were similar for stereochemically related trisaccharides.


Effects of fluoride and methanehydroxydiphosphate on enamel and on dentine demineralization.

The aim of this article was to investigate the effects of methanehydroxydiphosphonate (MHDP) and fluoride (F) separately and combined, on the demineralization process in enamel and in dentine under constant composition conditions. The demineralization was carried out in solutions containing 3 mM calcium, 3 mM phosphate, pH = 5.0, and either 6 microM MHDP, 12 microM F or 6 microM MHDP and 12 microM F. After demineralization periods (t) between 24 and 140 h, the lesion depth l and the mineral loss delta Z were measured by transverse microradiography of the enamel and dentine specimens. The amount of mineral lost during demineralization averaged over the lesion depth, R = delta Z/l, was calculated. R approximately 17 vol% for both enamel and dentine, both delta Z and l being greater for dentine than for enamel by approximately the same factor. The results show that under the same conditions dentine is attacked much more strongly than enamel. The lesion progress with time is quite different for the two tissues: in enamel the lesion depth progresses als l3 = alpha t + beta, in dentine as l2 = alpha't + beta'. The slopes alpha and alpha' decrease in the order MHDP > F > MHDP+F. In enamel the combined inhibitor effect is only slightly larger than the effect of F alone; in dentine the inhibiting effects of F and MHDP are approximately additive. The inhibitor interactions can be described by the Langmuir adsorption theory.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of occlusion on the fluoride distribution in rat molar cementum.

This study was undertaken to examine the influence of occlusion on the fluoride distribution in cementum following an experiment in which the occlusion in rats was locally altered by extracting the upper left molar. These and control rats with normal occlusion were given water containing 0 or 100 ppm fluoride for 12 weeks. The fluoride distributions in cementum from both first lower molars of the same animal were compared. The fluoride concentrations had increased throughout the tissue as a result of increased fluoride administration, irrespective of any changes in occlusion. They were, as usual, generally highest at or near the cementum surface and decrease towards the interior of the tissue. Where there had been a change in occlusion, the thickness of cementum was less than that of the contralateral tooth, but, despite this, the fluoride profiles in contralateral teeth were similar in both experimental and control rats. In the experimental rats, on the other hand, the total fluoride tended to be lower, and the mean fluoride tended to be higher in left molars without antagonists. These findings were never seen in the control rats. It was concluded that the alteration in occlusion influenced the fluoride distribution in the cementum through its effect on the rate of cementum formation.


Salivary clearance from different regions of the mouth in children.

The aim of this study was to evaluate the rates of salivary clearance at seven different locations in children. The diffusant was 1 mol/l KCl in a 1.0% agarose matrix, placed in small acrylic devices which could be fastened to the teeth with dental floss. The diffusion chambers were taken from the mouth at selected time intervals and the gels transferred quantitatively to flasks containing 400 ml of 100 ppm NaCl. The fluid was agitated intermittently for 1 h and analyzed for potassium by atomic absorption spectrophotometry. For 12 subjects (5 years of age), the clearance halftimes (the time for the initial potassium concentration to decrease by half) were lowest in the lower anterior lingual regions and were highest in the upper anterior buccal regions. When the salivary flow was stimulated, the clearance halftimes for the lower and upper anterior buccal sites in the 6 subjects without spaces between their anterior teeth were significantly higher than in the 6 subjects with spaces. The results show that the clearance halftime is longest for the upper anterior buccal site which is the site most prone to nursing bottle caries in the deciduous dentition.


Plaque formation in vivo and bacterial attachment in vitro on permanently hydrophobic and hydrophilic surfaces.

Highly hydrated polyethylene oxide (PEO) films represent one type of surface modification which may interfere with biofilm formation. Protein adsorption and saliva-mediated bacterial adherence were investigated in vitro on normal and hydrophobized glass surfaces and on glass surfaces with immobilized PEO films. More protein and bacteria bound to untreated compared to hydrophobized and PEO-treated glass. Pellicle and plaque formation was also studied in vivo on ceramic crown surfaces either untreated, hydrophobized or with immobilized PEO films. Pellicle and plaque formation was similar on the untreated ceramic and PEO surfaces. Less plaque seemed to collect on these surfaces compared to adjacent normal tooth surfaces. Almost no plaque accumulated on the hydrophobic crown surface and it was virtually devoid of stainable pellicle. Even after 7 days in the mouth without oral hygiene this surface was very hydrophobic and the disclosing solution could not spread.