Quantitative studies on the occurrence of praziquantel in milk and plasma of lactating women.

10 healthy lactating women were treated orally with the anthelmintic praziquantel (Biltricide), and the resulting timedependent concentrations of the unchanged substance in plasma and milk were determined simultaneously. 5 of the women ("1st trial") received the single dose of 50 mg/kg; the other 5 women ("2nd trial") were treated three times at 4 hour intervals with 20 mg/kg. During the 1st trial a maximal plasma-concentration of 1.30 mg/l (arithmetic mean) was found. Subsequently the mean plasma-concentration decreased continuously and after 24 h it was only 0.4% of the maximum. During the 2nd trial the highest mean value (1.92 mg/l) was found 10 h after the first administration; after 32 h (24 h after the last administration) the mean value was 0.6% of the maximum mean value. The mean areas under the concentration/time-curves were 5.25 h. mg/l and 13.8 h . mg/l, respectively. The plasma half-life was estimated to be 3 hours. In both trials the concentration/time-curves of the milk corresponded qualitatively to those of the plasma. However, in each person and at each time, the concentration in the milk were essentially lower than those in the plasma. On the average, the plasma-concentrations were four times higher than the milk-concentrations. The mean values of the milk-concentrations increased and decreased correspondingly with those of the plasma-concentrations. At the end of the investigation (24 and 32 h, respectively, from the beginning) they were lower than the limit of determination (4 microgram/l). The mean excretion with the milk of the 10 women was 0.0008% of the given dose. From the comparative concentration/time-course, it could be demonstrated that the milk does not represent a deep department but readily equilibrates with the plasma. Equilibration obviously takes place by passive diffusion and not by active secretion.


Increase in lifespan of rats following polypeptide pineal extract treatment.

The 20 month-long treatment of female rats with daily doses of 0.1 or 0.5 mg of polypeptide pineal extract (PPE) per animal increased their lifespan by 10 and 25%, respectively, as compared with controls. At the age of 16--18 months, 38% of control rats exhibited persistent disturbances in estral function (constant estrus or repeated pseudogestations), whereas these disorders were observed in 7% of experimental animals only. After administration of PPE to 16--18 month-old female rats checked for sterility by a two-week mating, a second mating period resulted in gestation development in four out of 16 animals and deliveries, accordingly. While chronic treatment with PPE did not affect the rate of neoplasm incidence, the mean age of tumour detection in the control group was 697 days and in experimental groups it was 811 and 868 days, respectively. Certain aspects of the interrelationship of rate of ageing, lifespan and specific age pathology are discussed.


[Iodine concentration in the blood and urine in children depending on the goiter size].

Epidemiological investigations have shown that at the Białystok Province about 30% of children and youth is afflicted with goitre. In this area drinking water is poor in iodine and iodine supply with food is quite unsatisfactory. The purpose of the present work has been to check the behaviour of the serum and urine iodine in children with thyroid goitre. The estimations of I in blood serum were made in 126 children with goitre (I, II, and III, according to the WHO classification) and in 100 healthy children. The method used included buthanol extraction according to Fisher and Morris. The concentration of iodine and its excretion rate in urine were assessed in 119 children with goitre of various advancement, an; in 170 children not affected with goitre, using the method of Fisher and Morris adopted to urine analysis. The authors found the following values for serum protein bound iodine: control group 4.9 microgram/100 ml, at average; 4.3 microgram/100 ml, 3.0 microgram/100 ml, and 2.6 microgram/100 ml in those affected with I, II, and III of the goitre, respectively. The 24 hr urine excretion rate of iodine in healthy children amounted to 66.4 microgram, and 64.2 microgram, 53.6 microgram, and 4o.2 microgram in those with I, II, and III goitre, respectively. The above results indicate a significant decrease of iodine concentration in blood serum and in urine in children with goitre; this decrease has been found to be dependent on the degree of the thyroid gland enlargement. The differences were statistically significant.


Clinical, hormonal and semiological data in adult men operated in childhood for hypospadias.

Examination of 16 adult men operated in childhood for hypospadias revealed signs of moderate injury of the male genital system. It appears that accessory sexual glands were mainly responsible for the observed abnormalities. Since testicular position and size, serum testosterone and FSH levels were normal it seems that hypospadias and the accompanied disturbances are connected with reduction of responsiveness of target tissues to androgen stimuli rather, than with lesion of the testicle. The coexistence of normal serum testosterone and elevation of serum LH suggests the decrease of sensitivity of hypothalamic or pituitary receptors to negative feedback influence of androgens. The consciousness of sexual inadequacy noted in some cases was mainly of emotional character.


Mutational analysis of natural alleles in and affecting the B incompatibility factor of Schizophyllum.

Primary mutations in the alleles of alpha 1 and beta 7 of the B incompatibility factor of Schizophyllum were induced with X rays. An additional mutation unlinked to the B factor and affecting its regulatory function was detected. This mutation is effective in monokaryons with most B-factor specificities. The spectra of induced mutations in different alleles is discussed in reference to a polarity in the expression of the recognition function and the regulatory function by each locus of the B incompatibility factor.


The ultrastructural morphology of leukemia L 1210 ascites tumor cells transplanted with different frequency.

The mouse lymphatic leukemia L 1210 ascites tumor cells were transplanted every 3rd (L1210/3) or 6th day (L 1210/6) and then examined by an electron microscope. In cytoplasm of L 1210 cells thick bundles of 8 nm filaments were observed. Lysosomes were more numerous in L 1210/6 cells. Results obtained from morphometric datas shown that the relative cell volume of L 1210/6 population was 1.59 time larger as compared with L 1210/3. The index of nuclear volume to cell volume was very similar in both populations. The relative volume of endoplasmic reticulum was more than twice larger in the L 1210/3 population. The cell surface area was larger in the L 1210/6 cells as compared with this in L 1210/3 cells, but the increase in the surface was not proportional to the increase of the cell volume. The relative surface area of endoplasmic reticulum cisternae was smaller in L 1210/6 cells than in L 1210/3 population.


The effect of hyperthyroidism induced by thyroideum siccatum on the central nervous system: an electron microscopic study.

Ten adult male rats were administered orally with thyroideum siccatum every day to produce a hyperfunctional state of thyroid hormone. They were examined electron microscopically for the fine structure of the brain. Clinically, experimental rats lost in weight, manifested a hyperactive, irritative attitude, and were in an aggressive state. Electron microscopically, the nerve cells showed a slight increase in the number of mitochondria in the frontal cortex, spiral and petaloid variation of ER in the thalamus. The specific findings in the experimental rats were variations of synapse observed in the frontal and temporal cortex, gyrus hippocampi, and thalamus, centering around the hypothalamus. They included meandering of the presynaptic membrane, formation of vacuoles by the presynaptic membrane, saccate projection of this membrane to the postsynapse, and changes in vacuoles which were torn off and fell into the dendrite. These variations occurred in the synaptic membrane and ER, probably because synthesis of the membrane had been accelerated remarkably by the action of thyroid hormones. They were considered to have brought about abnormalities to the conductive and transmission system. They seemed to be closely related with emotional disturbances and psychic symptoms, since such variations were particularly apparent in the hypothalamus.


[Transperitoneal fine needle biopsy of retroperitoneal lymph nodes in cancer diagnosis].

Preoperative lymphography was performed in 97 patients with urological malignoma. Fine needle punctions were performed of 458 suspicious as well as non-suspecious lymph nodes. In 22 cases lymphographic and cytological findings were compared with histological results after lymphadenectomy. It could be shown that of 15 cases with lymph node metastases lymphographic and cytologic findings were corresponding in 6 cases. In 9 cases tumor cells were found in lymph nodes even though the lymphogram was rated non-suspicious. It is concluded that fine needle biopsy of lymph nodes after lymphography is an important improvement in preoperative diagnosis of malignoma.


The effect of basic proteins on the haemostatic system of the dog.

Intravenous administration of histones or protamine to dogs resulted in a fall of the number of blood platelets, a lowered prothrombin consumption, a fall in the fibrinogen level, activation of the fibrinolytic system and deterioration of blood clot retraction.


The suckling-induced rise of plasma prolactin in lactating rats: its dependence on stage of lactation and litter size.

The response of plasma prolactin in vigorous suckling was measured in lactating rats which had been isolated for 10-12 h from their offspring. Plasma prolactin was investigated during suckling at various stages of lactation. The results demonstrate that prolactin responds maximally to suckling already in the first days of lactation. In the second half of the lactation period, the prolactin rise in the plasma induced by suckling decreases gradually; this is not due to a reduced suck-intensity of older pups. A relationship is found between the height of the suckling-induced prolactin rise and litter size. The data suggest that during suckling in the first weeks of lactation the pituitary secretes large amounts of prolactin at a constant rate. It is speculated that in the first minutes of suckling, receptors may clear considerable amounts of released prolactin from the circulation.


Serum thrombocytopoietic activity in thrombocytopenias.

By means of a bioassay performed in rats utilizing 75Se-selenomethionine as a platelet marker in vivo, serum thrombocytopoietic activity (STA) was determined in 9 healthy volunteers and in 82 patients with thrombocytopenia, viz. 27 cases of ITP (9 acute and 18 chronic), 19 of aplastic anaemia, 19 of acute leukaemia and 17 of chronic proliferative disorders. STA was the highest in the ITP group (p less than 0.01), particularly in the cases of short duration (p less than 0.001). In acute leukaemia, the STA was remarkably elevated (p less than 0.02) and a negative correlation between STA and blood platelet count could be demonstrated. A negative correlation between STA and the duration of thrombocytopenia was also found in the patients with ITP. No significant increase of STA was observed in patients with ITP after corticosteroid administration. In 5 out of 7 cases who responded satisfactorily to splenectomy a significant fall of STA was demonstrated after surgery. A slight, but statistically significant, rise of the STA value was found in patients with aplastic anaemia (p less than 0.05). No STA elevation was observed in the cases of chronic proliferative disorders with thrombocytopenia.


Sister chromatid exchanges in cultured peripheral lymphocytes from twins.

Sister chromatid exchange points (SCE points) on individual chromosomes were studied in cultured lymphocytes from 11 monozygotic (MZ) and nine dizygotic (DZ) same-sexed pairs by means of sequential Q-banding and BUdR-Giemsa techniques. No statistically significant variation between unrelated individuals with respect to SCE points on specific chromosomes was found. Intrapair differences in the number of SCE points on specific chromosomes were not significantly smaller between MZ twin partners as compared with DZ partners. The results suggest that genetic factors do not play any major role in the frequency and distribution of SCE in normal subjects.


Familial transmission of a translocation Y/14.

A translocation of heterochromatic material, brightly fluorescent after actinomycin D-DAPI staining, to the short arm of chromosome 14 was prenatally detected during cytogenetic examination of cells obtained by amniocentesis on the indication of advanced maternal age. Besides this abnormal chromosome, 43 autosomes and two X chromosomes were present. Silver staining made clear that an active nucleolus-organizing region was included in the translocation product. Both the intense fluorescence and the size of the translocated extra heterochromatic block were indicative of a Yq origin. Upon cytogenetic investigation of the parents, the mother appeared to carry the same t(Y;14) chromosome. Therefore, we expected a normal girl to be born. This was confirmed after birth.


Comparison of the intracellular lipids of cultured vascular endothelial cells and fibroblasts.

The lipids of human umbilical vein endothelial cells, calf aortic endothelial cells and foreskin fibroblasts have been compared. Cell cultures were established, and, upon confluency, the lipids were extracted and analyzed with respect to total lipid content, classes of lipids and total lipid fatty acid composition. The total quantity of lipid per milligram protein found in both human umbilical vein endothelium and calf aorta endothelium was similar to that found in fibroblasts grown in similar medium. Both types of endothelium contained the same major neutral lipid classes as fibroblasts, although they contained more phospholipid than did fibroblasts. The fatty acid composition of the three cells examined was influenced by cell type as well as the type of serum in the culture medium.


Canine rabies seasonality.

Data on births and oestrus cycles of 531 randomly sampled female dogs in Lima, Peru, were collected during 1974. Changes in the proportions of puppies in the canine population throughout the year were similar to the seasonal distribution of canine rabies. This finding has implication for the funding and thrust of any control programme.


Reimplantation of completely amputated rat limb.

A technique for the amputation and immediate reimplantation of rats legs was studied using a microsurgical technique. Complete survival of the reimplanted leg was achieved by basing the blood supply on anastomoses of arteries about 0.4 mm in external diameter. Anastomoses of vessels in that range by interrupted sutures of 10/0 and 11/0 black monofilament nylon proved to be compatible with leg survival. The ultimate survival of the reimplanted limbs depended upon microsurgical technique, preoperative and operative heparinization and external protection during the recovery phase. Animals are alive and using the replanted limb, several months postoperatively.


A comparative study of electrosurgical vs. cold urethrotomy in the treatment of urethral strictures.

Thirty-one patients with urethral stricture were subjected to internal urethrotomy under visual control. The patients were divided into two groups according to the surgical procedure: electrosurgical or cold resection. A modification of the Sachse knife was introduced in order to permit its use with the American Cystoscope Makers Inc. instruments. The success rate with cold resection was 81.81% and with the electrosurgical procedure 40%. Internal urethrotomy with cold resection is a simple and harmless operation, being a first choice in the treatment of urethral stricture.


[Experiences with CO2-laser-surgery in otorhinolaryngology (author's transl)].

Experiences with 70 CO2-laser procedures are reported. 39 operations were performed in the larynx, 7 in the pharynx, 4 in the oral cavity; 19 were tonsillectomies and 1 the excision of an exophytic skin tumor. The advantages of the CO2-laser-surgery are: minimal hemorrhage during surgery, excellent visibility in the operative field, slight postoperative edema and reduced postoperative pain. Surgery with the CO-2-laser beam is best performed for the following indications: endolaryngeal microsurgery, procedures in highly vascularized organs (tongue) or on well vascularized tumors (hemangioma), operations in hemophiliacs.


Mitotic rate of thyroid follicular cells in untreated and goitrogen-treated rats: variation with time of day.

The paper presents the results of investigations into the mitotic rates of thyroid follicular cells of adult male rats maintained under controlled conditions of temperature, photoperiod and handling. The mitotic rate in eight successive 3 hour periods of the day showed a clear mitotic rhythm, with a maximum at 12.00--15.00 hours in untreated rats. The mitotic rate over the 24 hour period was 7.6+/-0.83(S.E.)metaphases/10000 cells/hour. Rats treated with the antithyroid drug, carbimazole, for three weeks were manifestly hypothyroid, as shown by decreases in oxygen consumption and rate of growth. With carbimazole the mitotic rate of the thyroid follicular cells was increased three-fold, and the mitotic rhythm was no longer detectable. In an experiment to test the efficiency of vincristine sulphate, the accumulation of metaphases after 1 mg/kg or 2 mg/kg vincristine was linear for 0.5--8 hours, although, at the higher dose, the number of metaphases was reduced after 8 hours. The mean daily mitotic rate in untreated rats was approximately commensurate with the rate of increase of body weight, which supports the classification of follicular cells as an 'expanding cell population'.


High resolution scanning electron microscopy of elastic cartilage.

The elastic cartilage of the rat epiglottis was studied with a high-resolution SEM technique. The chondrocytes were found to be anchored in their lacunae by fibrils running in from the territorial matrix. This matrix exhibited a dense network of fibrils arranged tangentially around the lacunar cavity. The fibrils of the inter-territorial matrix however, formed a three dimensional network of sheets with interconnecting fibrils. The SEM has shown up for the first time a substructure in the fibrils in the form of circular protuberances arranged circumferentially around the fibrils and forming ridges 12--19 nm apart. We suggest that the fibrils are collagen, and the protuberances are the proteoglycans attached to the collagen fibrils. Globules seen attached to the fibrils are most probably 'matrix granules' as observed in other kinds of cartilage. The total inability to visualize elastin with the high resolution SEM is puzzling.


Mechanisms of smooth muscle antibody production: a clinical study in children with infections, haemolytic syndromes, and idiopathic thrombocytopenic purpura.

Sera from 530 children suffering from various diseases and from 64 controls were tested for smooth muscle autoantibodies (SMA) by indirect immunofluorescence. A high incidence of SMA (51-86%) was found in patients with viral and bacterial infections (viral hepatitis, infectious mononucleosis, measles, mumps, chickenpox, typhoid fever, and brucellosis), independently of liver invovlvement, and in patients with acute haemolytic anaemia due to G-6-PD deficiency (48%). By contrast, the incidence of SMA from patients with beta-thalassaemia major and idiopathic thrombocytopenic purpura was no higher than in the controls. The discrepancy in incidence in haemolytic anaemias due to different causes may reflect the effect of endogenous and extrinsic agents. In the viral infections, SMA were mainly of the IgM class and gave an 'SMA-V' staining pattern. In bacterial infections (typhoid fever and brucellosis), SMA were either IgG only or IgM and IgG, and the staining pattern was also mainly 'SMA-V'. In infections which affect or may affect the liver (viral hepatitis, infectious mononucleosis, typhoid fever, and brucellosis), SMA was present at high titres (1:80-1:320), whereas in infections not affecting the liver (measles, mumps, and chickenpox) the titres were lower (less than or equal to 1:80). In most patients SMA occurred transiently and without apparent pathogenetic significance. The antigen against which infection-induced SMA is directed is not actin; its nature has yet to be identified.


How concentrate feeding affects glucoregulatory hormones in ruminants: implications in bovine ketosis.

Twenty-four feedlot steers and four sheep were fed roughage or grain rations while three other sheep received intraduodenal infusions of amino acids, glucose, volatile fatty acids, and proteins to determine whether the release of plasma glucagon-like immunoreactivity is influenced by dietary factors and the composition of duodenal chyme. Plasma glucagon-like immunoreactivity rose in both cattle and sheep as the proportion of grain in their rations was increased. In response to intraduodenal infusions, only glucose stimulated glucagon-like immunoreactivity release. These experiments demonstrate that plasma glucagon-like immunoreactivity concentrations change in cattle and sheep in response to the amount of grain consumed and that glucagon-like immunoreactivity release is triggered by glucose in intestinal chyme.


Oral nicotinic acid as a treatment for ketosis.

Changes in blood metabolites and milk production were measured in eight cows with subclinical or clinical ketosis following treatment with daily doses of 12 g nicotinic acid fed with the concentrate mixture. Ketotic cows displayed a positive milk ketone test, reduced milk production and feed intake, hypoglycemia, hyperketonemia, and elevated free fatty acids in plasma. The milk ketone test was negative in all cows 5 to 9 days following initiation of treatment. After 7 days of treatment, milk production and glucose in plasma were increased while there were decreases in plasma beta-hydroxybutyrate and free fatty acids. No relapses occurred.


Quantitative regularities of development of endogenous infection in irradiated organism (survey of literature).

Statistical analysis of data from the literature and the author's own experimental results was carried out in order to reveal functional dependence between the dose of irradiation and the development of endogenous infection in an irradiated organism. Direct linear dependence was established between the dose of irradiation and the severity of endogenous infection at doses causing death from the "bone-marrow" syndrome in acute radiation sickness. In the case of death from the "intestinal" syndrome, inverse linear dependence can be observed between the dose of irradiation and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the course of acute radiation disease. The importance of endogenous infection in death of the organism is neutralized after irradiation in doses causing death "under the ray".


Epidemic of acute haemorrhagic conjunctivitis in Freetown, Sierra Leone, in 1970.

Epidemiological features of the epidemic of acute haemorrhagic conjunctivitis in Freetown, Sierra Leone, in 1970, are described. On the basis of hospital figures and a House-to -House survey of 0.9% of the population it is estimated that 50-53% of Freetown's population suffered from the conjunctivitis in 20 weeks. Though no causative agent was isolated, it is supposed, on the basis of the striking similarity with other outbreaks, that the epidemic was caused by enterovirus type 70. Hospital figures, a house-to-house survey and a survey in a closed community provided evidence that man-to-man contact was the principal mode of spread.


Prospective study on streptococcal pharyngitis among a town population.

A one-year-round study on pharyngitis incidence among the general population of a town (24,300 inhabitants) was carried out. All patients, with pharyngitis who visited health centres were examined clinically and mcirobiologically. The overall pharyngitis incidence rate and the streptococcal pharyngitis incidence rate were, respectively, 8.3 and 3.9 cases per 100 population. Age-related incidence was highest in the group of 5-10 years, seasonal incidence was highest in autumn. Clinical diagnoses made preliminary to bacteriological examination were correct in only a half of the streptococcal pharyngitis cases. The accuracy of clinical diagnosis of streptococcal pharyngitis could, at best, be raised to 80% if fever of less than or equal to 38.0 degrees C and presence of exudate on tonsils should be considered significant criteria. A great majority of the streptococcal pharyngitis cases were caused by group A streptococci; the prevailing  M types were 12, 1 and 3. Emphasis is laid on the necessity of performing microbiological examination of all pharyngitis cases in order to ensure etiological diagnosis and causal therapy. 15)


Prevalence of ornithosis and other Chlamydia-like infections in the Ukrainian SSR.

The prevalence of ornithosis and other Chlamydia infections among various groups of the population, some species of birds and mammals was studied in several regions of the Ukrainian SSR. Among the town population having no occupational contact with domestic fowl and farm animals, complement-fixing antibodies to group ornithosis antigen were found in 6.5% of the examined, among the inhabitants of rural localities in 8.4% and among the workers of poultry farms in 19.9%. During the examination of the immunological state of the workers of cattle-breeding farms, antibodies were detected in 15.1%. Pigeons, hens and ducks were investigated as probable sources of infection. The number of positively reacting individuals was 53.7, 13,7 and 24.9%, respectively. This indicates that they play a role in the spread of infection. The obtained data point out a considerable spread of Chlamydia infections among farm animals. Positive results of serological examination were recorded in pigs in 25.7%, in calves in 15.1% and in 8.6% of cases examined.


Testosterone-estradiol-binding globulin, unbound and total estradiol and testosterone, and total progesterone during the menstrual cycle in women with epilepsy taking antiepileptic drugs.

Total plasma estradiol, progesterone, testosterone, and the binding capacity of testosterone-estradiol-binding globulin (TeBG) were measured and plasma unbound estradiol and testosterone calculated, every second day during nine cycles in six patients with epilepsy. They all received phenytoin as one medication. Some had additionally, phenobarbital or ethosuximide. Plasma concentrations were compared with those of a group of healthy women without medication. Total plasma testosterone and TeBG binding capacity were significantly increased in the treated group, as compared to the control group. However, the unbound testosterone concentration was within the range of the controls. The percentage unbound testosterone of total plasma concentration was clearly below that of the control group. This indicates that there was a primarily increased TeBG binding capacity in patients taking antiepileptic drugs.


Circannual changes in plasma concentrations of immunoreactive retinol-binding protein and luteinizing hormone in male and female Japanese quail.

In a single experiment, lasting for 18 months, male and female quail were exposed to an annual cycle of artificial photoperiod synchronized with sunrise and sunset, and their plasma levels of immunoreactive retinol-binding protein (IRBP) and LH were monitored at frequent intervals. Plasma levels of both IRBP and LH showed a repeating annual cycle with maximal levels during the spring/summer, the period of reproductive activity and highest rate of egg-laying, and minimal levels during the autumn/winter. Plasma levels of IRBP and LH were significantly, but only weakly, correlated with each other. The possible role of LH in the regulation of plasma IRBP during reproduction is discussed. Evidence is presented that the proportion of IRBP which does not carry retinol (retinol-binding apoprotein; apoRBP) varies throughout the female breeding cycle and that the high apoRBP concentration noted in the spring/summer period may be related to the deposition of retinol in the egg.


Suppression of pituitary secretion of follicle-stimulating hormone by porcine follicular fluid during pro-oestrus and oestrus in the rat: effects on gonadotrophin and steroid secretion, follicular development and ovulation during the following cycle.

In this study, we have examined whether the suppression of raised plasma FSH concentrations at pro-oestrus and/or oestrus by porcine follicular fluid (PFF) affected the development of follicles for ovulation in the next cycle. Adult, 4-day-cyclic rats were injected with PFF or pig serum at various hours of pro-oestrus and oestrus. Plasma FSH levels were suppressed following PFF treatment at any time of pro-oestrus and oestrus. Furthermore, this suppression was always followed by a 'rebound' increase in plasma FSH. In contrast, plasma LH concentrations were unaffected by PFF treatment and neither gonadotrophin was altered by treatment with pig serum. When rats treated with PFF or pig serum were allowed to complete one additional cycle, plasma LH and FSH concentrations at the pro-oestrus and oestrus after treatment were not significantly different among groups regardless of treatment or time of treatment. All ovaries of rats treated with PFF or pig serum on the next pro-oestrus morning before ovulation were histologically similar. Furthermore, all animals ovulated a normal complement of ova at the next oestrus regardless of whether preovulatory, secondary or both increases of plasma FSH had been blocked by PFF treatment during the previous cycle. However, animals given PFF during the preceding cycle, plasma oestradiol and progesterone concentrations were significantly altered on the morning and afternoon of pro-oestrus respectively. These results suggest that increased plasma FSH concentrations at pro-oestrus and oestrus may not be essential for folliculogenesis and ovulation in the subsequent cycle. Alternatively, the 'rebound' of FSH on day 1 of dioestrus after the suppression of both phases of FSH secretion at pro-oestrus and oestrus may be sufficient to provide ovulatory follicles for the next pro-oestrous day.


A cellular mechanism for the palatal shelf reorientation from a vertical to a horizontal plane in hamster: light and electron microscopic study.

Cellular and subcellular events during reorientation of the palatal shelf in hamster fetuses are described. An alteration in the morphology of the epithelial and the mesenchymal cells is observed during shelf realignment from a vertical to a horizontal plane. The mesenchymal cells elongate and subsequently appear to protrude in the medially bulging palatal shelf. Microtubules, microfilaments and close contacts are associated with elongation of the mesenchymal cells. The cells of the thickened epithelium may play a mechanical role in providing direction to the mesenchymal cells during palatal shelf reorientation. The altered morphology of the mesenchymal cells may be associated with the intrinsic shelf force implicit in Walker and Fraser's theory of palatal shelf reorientation.


[Recessive microencephaly linked to the X chromosome].

A family with X-linked recessive microcephaly is reported. As patients there were found 8 men or boys respectively out of 3 generations, all of them being related by their mentally healthy mothers. Besides microcephaly the patients showed growth retardation and obesity. Some of them, in addition, had various anomalies as inguinal or umbilical hernias, cryptorchism, tapering fingers, contractures, deeply rooted thumbs and club-feet. There were no hints for a metabolic defect or a chromosomal aberration. The dermatoglyphics could be investigated in 5 patients and showed in all of them a shifting of the axial triradius into the distal position t'. Comparing the own findings with case reports on X-linked microcephalies, the above mentioned family was found not to correspond to any of these observations. It is assumed that in this family, a new disease has occurred which until now has not yet been described, so that the X-linked microcephalies seem to be a heterogenous group of disease from the genetic point of view.


A case of complete testicular feminisation and 47,XXY karyotype.

A very rare case of complete testicular feminisation with a 47,XXY sex chromosome complement is described. The X-chromatin is positive. The subject studied, who belongs to a family in which four other members have Morris's syndrome and have a 46,XY karyotype, is a perfect phenotypic female. The endocrine situation is unique and resembles, in part, that of subjects with Klinefelter's syndrome.


Antagonism by naloxone of tolerance and dependence in mice given a single dose of morphine.

The effect of naloxone given at various times after morphine administration on the development of tolerance to and dependence on a single dose of morphine was studied. Naloxone antagonized the analgesic effect of morphine and the development of tolerance to and dependence on morphine, dose dependently. The time course of the development of tolerance to a single dose of morphine almost paralleled that of dependence on morphine but the time course of the disappearance of tolerance did not coincide with that of dependence. When start of the duration of action of morphine was blocked by naloxone for various time intervals, the degree of tolerance to and dependence on morphine was antagonized, time dependently. When the end of the duration of action of morphine was antagonized by naloxone for various time intervals, tolerance and dependence which developed up to that time was completely antagonized by naloxone.


Mode of antagonistic action of levallorphan in morphine-dependent rats and assessment of physical dependence liability.

The antagonistic mode of levallorphan in rats dependent on morphine or codeine was studied from the viewpoints of the doses of morphine and the lengths of administration and also from the standpoint of timing of the challenge. In morphine-dependent rats on morphine-admixed food (60--100 mg/kg/day) for 1, 3 and 6 weeks, the rate of maximum weight loss on application of levallorphan (2 mg/kg, s.c.) did not correlate with the length of morphine treatment. The rate of weight loss on single application of levallorphan 0, 6, 12 or 24 hours after withdrawal or morphine was lower with the passage of time after the withdrawal. Rats which were given levallorphan 3 times in succession, i.e., at 0, 5 and 10 hours after morphine withdrawal showed such a pattern of weight loss that the first application of levallorphan resulted in 7% loss, while with the second and third applications there was little weight loss. Despite the continued withdrawal, the animals began to gain body weight as early as 14 hour, and body weight was totally recovered before the withdrawal in 24 hour. In conclusion, it is advisable to challenge with levallorphan at 0 hour of withdrawal to obtain qualitative and reproducible results. In addition, the application of levallorphan to morphine-dependent rats at adequate intervals provides for the early recovery of abstinence signs.


[Schaemic necrosis of urethra after repeat surgical attempt at the correction of stress incontinence. Vesicocervicoplasty (author's transl)].

This patient had been operated upon 3 times unsuccessfully for stress incontinence (buttressing of the bladder neck by the vaginal route, the first time); almost entire urethra has been lost. Neourethra reconstructed from bladder neck muscle and sling procedure. Total continenece preserved. 35 years follow-up.


Eating pattern of morphine dependent rats.

To analyze the drug ingestion patterns of rats in the course of dependence development while on the drug-admixed food (DAF) method, an automatic food intake measuring apparatus was developed. Rats were put on morphine-admixed food, and the food ingestion patterns were recorded with the apparatus in the course of dependence development, during drug withdrawal and at the time of challenge with levallorphan. The naive rats ate the regular diet intermittently at night, and the eating time of morphine-treated rats was longer than that of naive rats. The treated rats also exhibited a frequent eating behavior after 4--5 days on the morphine treatment. During morphine withdrawal, the animal gradually ate the regular diet at about 1-hour intervals, even after evolvement of abstinence signs. When the morphine-dependent rats were given levallorphan, they neither ate nor approached to the food for the first 2--3 hours, but after this time, showed abrupt increases in these activities. Thus, the drug intake pattern of rats in the course of morphine dependence development suggests a correlation between the stage of development of physical dependence and the stage when the animals frequently eat the drug-admixed food.


[Pyosalpinx].

A hundred-and-fourteen women with pyosalpinx, treated in the Varazdin hospital, are presented. The youngest patient was 16 and the oldest 63 years old. According to case history, 28 women denied having been pregnant. Eighty-one women (71%) were treated only with puncture and instillation and 33 (29%) surgically. Among the latter, 12 were surgically treated for peritonitis or under the picture of appendicitis at the Surgical Department. Surgical interventions ranged from unilateral adnexectomy to bilateral adnexectomy with hysterectomy, depending on age, the extent of the process, and other findings (myoma, carcinoma, etc.).


[Intrauterine growth retardation of newborns with congenital anomalies].

The authors examined 11,799 newborns whose intrauterine life lasted from 28 to 42 weeks. In the group of dysmature infants (443) malformations were present in 11% and in the group of prematures (841) in 4.3%. Malformations were divided according to localization. The most significant difference was observed in the occurrence of malformations of the extremities (dysmature infants 27.17% and prematures 15.79%). It is concluded that malformations appear to be considerably more frequent in dismature infants than in prematures and that by their presence they affect the child's intrauterine growth.


The local immune response in the mammary gland of the sow following infusion of a protein antigen.

A study was made of the local immune response in the udder of the sow following infusion of a soluble antigen. Four mammary glands of each of four pregnant sows were infused with ferritin prepartum. Samples of blood, colostrum, and milk were collected during the following lactation; animals were slaughtered and mammary tissue removed for immunohistology. Blood, colostrum, milk, and mammary tissues were similarly collected from nonimmunized (control) sows. Colostral and milk whey from immunized sows contained higher levels of immunoglobulins than whey from control sows. There was an increase in numbers of IgA-containing plasma cells and total lymphoid cells in mammary tissue of immunized sows compared with controls. The results suggested that the local immune response was at least as great in non-infused glands as infused glands of immunized sows.


Multiple sclerosis : is it transplacentally induced?

The aetiology of multiple sclerosis MS is not known. Most research workers believe a viral aetiology. An alternate theory - namely transplacental induction of MS is outlined. Correlative evidence is drawn from epidemiological studies, models of transplacentally induced conditions, metabolic disturbances in utero that can affect myelin development or result in offspring with defective immunological competence and surveillance. The relationship between B group vitamin deficiencies and mineral deficiencies and MS is considered. Primary, secondary and tertiary prevention of MS in view of this theory is outlined.


Pig Bel.

Pig Bel is a form of acute, segmental, necrotizing enteritis presenting as a common and life-threatening disease among the people (particularly the children) of the Highlands of Papua New Guinea. It relates to the consumption of pig meat and is thought to be caused by Clostridium welchii type C (an organism not usually present in the human intestine), the organism being transmitted to man by means of contaminated pig meat. Pig Bel resembles the diseases called "Darmbrand" which occurred in Northern Germany in the years that immediately followed World War II. Darmbrand was associated with a Clostridium welchii infection, possibly precipitated by malnutrition. It disappeared within a few years of its recognition. Conditions that closely resemble the clinical and pathological features of Pig Bel have been reported from Uganda and Thailand. In these countries, only a few cases have been encountered and they have not been associated with the eating of pig meat or with a clostridial infection.


Primary culture of mammalian nephron epithelia: requirements for cell outgrowth and proliferation from defined explanted nephron segments.

Nephron segments were dissected from fetal or from early postnatal rabbit kidneys (n = 86) and explanted individually into primary tissue culture. Outgrowth of epithelioid cells and proliferation in monolayers from the collecting tubule and the thick ascending limb of Henle's loop occurred regularly if a special substratum and matrix were used. Media were either supplemented with non-proteins (defined media) or with embryo extract and fetal sera (undefined media). Outgrowth and monolayer spreading were recorded by Differential Interference Contrast Microscopy. Monolayer cells resemble those seen with the same recording technique during tubule in vitro perfusion. Undefined media were essential for growth of convoluted tubule segments from embryonic Nephron Anlagen and outgrowth of cells from proximal straight tubules, in contrast to the distal nephron segments. The specific functional and morphological properties of cells derived from primary culture of nephron segments are under study.


[Angiosarcoma of the breast. Apropos of a case].

A case of angiosarcoma of the breast is described. This is an unusual, malignant, vascular tumour observed in young, fertile women. Its aetiopathogenesis, histological picture and pathological anatomy are described, and reference is made to the deceptively benign nature it often displays initially, its diagnosis, and its clinical picture. Emphasis is also placed on the limited possibilities of treatment, and its dependence on the earliest possible diagnosis for a certain degree of validity.


Influence of replacement of chloride by sulphate upon urine excretion and glomerular filtration rate in blood perfused isolated dog kidneys.

Tubular reabsorption was inhibited in isolated dog kidneys by the progressive substitution of plasma chloride by sulphate. In the absence of antidiuretic hormone activity, urine output remained unchanged owing to an equivalent decrease in glomerular filtration rate. This equilibrium was demonstrated under conditions of "saline natriuresis" and was not disturbed by furosemide. Although the impairment of glomerular filtration rate was accompanied by a decrease of total renal blood flow, the equilibrium was not disrupted by angiotensin antagonism. Sodium excretion was enhanced by low plasma chloride concentrations in the absence, but not in the presence of furosemide. The results are not compatible with a specific role of osmolality, sodium or chloride concentrations in the tubular fluid in the adjustment of glomerular filtration. Simultaneous changes in blood flow and tubular flow resistances might explain the results. It is suggested that, in contrast to the mechanism of tubulo-glomerular feedback found in individual nephrons of hydropenic animals, this intrarenal mechanism might serve to protect the organism against sodium loss under conditions of high intake.


Parallel between antianxiety and cardiovascular effects of chlordiazepoxide in genetically nervous dogs.

There is evidence that cardiac arrhythmias are partially of CNS origin, and that certain drugs affect arrhythmia, both positively and negatively, through CNS action. We hypothesized and confirmed that chlordiazepoxide diminished the well-established incidence of arrhythmias (A-V blocks and nodal escapes) in five nervous pointer dogs. It is known that this drug normalizes behavior and aids in the bar-pressing performance of nervous dogs. Nervous dogs tend to have low heart rates (HRs) while normals have higher HRs. Chlordiazepoxide increased HRs in our five nervous dogs, and we postulated that HR increase would be less or none in normals. This was confirmed in a later study of five normals. A further study of eight normal dogs and eight nervous dogs essentially reproduced these findings, suggesting the possibility that the slow heart rates and the behavioral abnormality have a common basis, expected to be some CNS biochemical lesion.


Thermogenesis and thermolysis during sleeping and waking in the rat.

Thermogenesis (VO2), sensible heat loss and subcutaneous back temperature were recorded simultaneously during sleeping and waking in both intact and depilated rats at Ra ranging from 21--28 degrees C. VO2 increased during wakefulness (W), decreased and plateaued during slow wave sleep (SWS) and then decreased 10% with each paradoxical sleep (PS) phase. Sensible heat loss, which represented about 90% of the heat production, increased and plateaued during SWS, decreased in W and generally rose abruptly (+40%) during PS. After removal of the fur the mean levels of VO2 and sensible heat loss were increased by 20--50% and returned to normal values within two weeks, although their variations related to stages of sleep were unchanged. These results concerning thermogenesis and thermolysis are in agreement with the variations of body temperature (brain excluded) during sleeping and waking.


Microsphere size and determination of intrarenal blood flow distribution in the rat.

The influence of microsphere size upon the estimation of cardiac output (CO), renal blood flow (RBF) and its cortical distribution (ICBFD) was evaluated by simultaneous injection of 8.5 +/- 0.8 micrometer (SD) and 12.7 +/- 1.7 micrometer (SD) spheres in control conditions and after hemorrhagic hypotension (HH rats). The values of CO and RBF were unaffected whilst the ratio of flow to outer and inner halves of cortex (OCF/ICF) was 32% higher with 12.7 micrometer than with 8.5 micrometer spheres in both groups. Microscopic analysis of cleared kidneys slices confirmed that large spheres were more concentrated in outermost and less concentrated in innermost glomeruli than small spheres. In addition, the ratio of sphere number per outermost to that per innermost glomerulus (fs/fjm), and approximation of glomerular blood flow distribution was 1.74 and 1.76 with large spheres and 0.98 and 1.06 with small spheres in control and HH rats respectively. It is concluded that the artifact due to sphere size was not minimized in low flow conditions (HH rats) and that 8.5 micrometer spheres may be a more realistic marker of glomerular blood flow distribution in the rat than 12.7 micrometer spheres.


A continuous wave Doppler velocimeter for monitoring blood flow in the popliteal artery, compared with venous occlusion plethysmography of the calf.

A transcutaneous Doppler velocimeter has been used for monitoring changes in blood flow in the popliteal artery during and after exercise of the calf muscles on a calf-ergometer. The instrument and the positioning of the probe are described. The validity of the Doppler measurements has been assessed by comparing results after exercise and after 5 min arterial occlusion with venous occlusion plethysmography. For 10 healthy volunteers calibration lines were found which are curved. This can be ascribed partly to alinearity of the Doppler instrument and partly to changes of the diameter of the popliteal artery. Displacement of the probe with respect to the artery, which influences the measured velocity signal, can be detected and to a certain extent corrected by taking into account the intensity of the Doppler signal. The largest deviation of a data point from the corresponding calibration line varies for the ten subjects between 90 and 170 Hz in the high flow range (mean Doppler frequency around 1000 Hz) and between 20 and 60 Hz in the low flow range (mean Doppler frequency below 200 Hz).


Salivary cooling, escape reaction and heat pain in capsaicin-desensitized rats.

Salivary thermolytic mechanisms (weight of salivary glands, effect of desalivation on water intake and body temperature, grooming activity) as well as escape behaviour and reaction to heat pain were studied in capsaicin-desensitized and control rats exposed to various warm ambient temperatures. Body temperature of the desensitized rats increased more than the controls' at all the ambient temperatures studied (32, 34 and 36 degrees C); however, significant differences in the mechanism of salivary cooling were obtained only at 34 and 36 degrees C. Central impairment of saliva spreading in desensitized rats seems evident. Complete surgical desalivation did not increase hyperthermia of control and desensitized animals in warm environments. Therefore other mechanisms, primarily vasodilatatory, must also be involved in the rat's thermolytic normal response. Although desensitized rats did not show a tendency to escape from the warm environment their response to heat pain was normal. In conclusion, it is suggested that heat perception in desensitized animals is impaired; however, the existence of some capsaicin-insensitive thermolytic mechanisms (prone extension of the body) cannot be excluded.


Blockade of pressor responses to angiotensins I and II and noradrenaline using phentolamine, propranolol and hexamethonium in conscious rabbits.

Angiotensin I is known to have direct agonist activity at some target tissues, independent of its conversion to angiotensin II. Aspects of its possible direct role as a pressor agent were investigated in conscious rabbits. Phentolamine (3 mg/kg i.v.), a dose which did not affect baseline blood pressure, reduced the pressor response to angiotensin II by 17% (P less than 0.05) but did not alter the sensitivity to angiotensin I. Noradrenaline activity was reduced by 56%. Propranolol (2 mg/kg i.v.), a dose which did not affect baseline blood pressure but which substantially reduced the depressor response to isoprenaline, had no effect on the pressor activity of either angiotensin I or II. Noradrenaline potency was reduced by 32%. Hexamethonium (20 mg/kg i.v.), caused a potentiation of the response to angiotensin I and II and noradrenaline. This was probably a non-specific action associated with the decrease in baseline blood pressure. No differential effect of ganglion blockade on the two angiotensins was noted. The dissociation of the effects of phentolamine on angiotensins I and II provides further evidence that pressor actions of these two compounds act through partially different mechanisms.


A new and simple technique for the generation of visual evoked potentials in freely moving animals.

A new and simple technique for the generation of visual evoked brain-potentials (VEP) by the aid of a light-emitting diode (LED) is presented. The method allows the generation of VEPs in freely moving animals under constant stimulation conditions and prevents moreover any acoustic disturbances.


Changes in liquid-junction potential following chloride replacement in cat papillary muscle.

The transient depolarizations in cat papillary muscle produced by chloride substitution with low mobility anions are largely due to changes in liquid-junction potential at the tissue level.


Sulfur amino acid and methyl donor status of corn-soy diets fed to starting broiler chicks and turkey poults.

Experiments were conducted to determine the effects of supplementing corn-soy-bean meal-white grease diets with sulfur amino acids and methyl group donors for starting broiler-strain chicks. The diets (23% protein and 3200 kcal ME/kg) were fed to quadruplicate lots of chicks in battery brooders. The diets were calculated to contain .37% methionine, .37% cystine, and 1499 mg/kg choline. Chemical and microbiological assays yielded values of .32% and .42% for methionine and cystine content respectively. Results of 5 chick experiments showed that supplementing this diet with .23% DL-methionine significantly (P less than .05) improved 3 week-gain (375 vs. 415 g) and feed/gain (1.54 vs. 1.47) over that obtained with the basal diet. When L-cystine and 2(CaSO4).H2O failed to give a significant (P greater than .05) response, compounds capable of donating methyl groups were fed. Significant (P less than .05) responses in gain (404 and 420) and feed/gain (1.48 and 1.51) over the basal were obtained with choline and betaine. These responses were not significantly (P greater than .05) different from that obtained with methionine. Serine and sodium formate failed to give consistent responses. Using a poult diet of 28% protein and 2800 kcal ME/kg, a significant (P less than .05) response to DL-methionine was again observed, with intermediate responses to betaine, choline, and serine. It is concluded that (within the limits of the experimental model) corn-soy type diets contain an adequate amount of total sulfur amino acid for chicks, but not poults, when sufficient choline or betaine are provided.


Effect of cued and uncued inescapable shock on voluntary alcohol consumption in rats.

Rats were given cued and uncued inescapable shock; their voluntary alcohol intake was compared to a group given a yoked cue but no shock. Results suggested that, unlike uncued inescapable shock, cued inescapable shock caused an increase in voluntary alcohol intake, although the increase was insufficient to produce overt inebriation. It was suggested that the increase which occurred was due to a combination of adjunctive drinking and a gustatory and olfactory discrimination breakdown, both occurring in direct response to shock.


A frequency analysis of behavior components of the serotonin syndrome produced by p-chloroamphetamine.

A time-sampling frequency analysis was made of criterion behaviors following injection of 2.5--10 mg/kg dosages of p-chloroamphetamine (PCA). Stereotypic behaviors (forepaw treading, circling, head weaving and inching) increased with increasing dosages and normal behaviors (grooming, rearing, and instances of inactivity) decreased. Composite scores of stereotypic behavior were a positive, linear function of PCA dosage. Composite scores of normal behavior showed near maximal inhibition at 5 mg/kg. Splayed hindlimbs is a reliable and sensitive indicator of PCA action, but vocalization, tremors, diarrhea and autonomic signs are not. Preinjection of PCA strongly attenuated the PCA-induec syndrome, as expected, since the preinjection should deplete brain serotonin and reduce the amount released by the second PCA injection.


Morphine and naloxone's effects on sexual behavior of the female golden hamster.

The effects of morphine and naloxone were observed after administration to female golden hamsters (Mesocricetus auratus). Large doses of morphine, 80 mg/kg, consistently produced sedation and behavioral depression of responses to nociceptive stimuli. Smaller doses of morphine (e.g., 10 mg/kg), that produced few other behavioral changes, suppressed a measure of female sexual responding. The suppressive effects on sexual behavior were reversed by 4 mg/kg of naloxone. Morphine administered intracerebroventricularly had little effect on sexual responding, even at doses which produced other side effects. Doses of 4 and 8 mg/kg of naloxone in opioid-naive subjects did not reliably alter sexual responding up to 2 hr after administration. These observations lead to the suggestion that morphine produces effects which are incompatible with full sexual functioning in female hamsters.


Behavioral antecedents of cocaine-induced stereotypy.

The effect of cocaine on discriminative behavior was determined in a study in which the subjects' ongoing behavior at the time of drug administration was manipulated. Cats were trained in a discrimination task where bar-pressing when a tone was present (S+) resulted in milk reinforcement. When the tone was absent (S-) milk was not delivered. The duration of these periods varied randomly during 30-min sessions and responses during S- delayed the next trial. Once a high level of discrimination was achieved, drug testing was begun. Ongoing behavior was manipulated by scheduling either a 5-min S+ or S- period immediately after cocaine injection (1 mg/kg). When S+ followed cocaine, stereotyped bar-pressing developed with markedly increased responding during the remainder of the session. In contrast, when S- followed cocaine, suppression of bar-pressing developed. The effect could be reversed in most subjects when stimulus conditions were later reversed. A similar experiment using rats yielded similar results. These results indicate that ongoing behavior and stimulus conditions are critically important in determining the behavioral effects of cocaine.


HLA antigens in immunologic thrombocytopenic purpura (ITP).

79 patients with definite ITP were investigated for HLA-A, -B, -C antigens. There was an increased frequencey of HLA-B5 in the entire groups (27.8% vs. 16.5% in controls and for HLA-B12 in male patients. However, after correction for the number of antigens tested, the difference of antigen frequencies became insignificant.


Zinc status in normal Thai infants and children.

Serum zinc levels in Thai infants and children from newborn to 14 years were studied. Data showed that serum zinc levels of infants were significantly lower than that of children (P less than 0.0005) although serum zinc levels in infants were low. They appeared to have normal growth and development. Beyond one year of age serum zinc levels increased with increasing age and there was no reduction in serum zinc level in pubertal subjects. Serum retinol binding protein was also studied. It was found to be low at birth and started to increased in the age of 1--5 months, the relationship between serum zinc and serum RBP was not apparent either in the younger age groups or in adult population.


A survey on intestinal parasitic infections in Laotian refugees at Ubon Province, Northeastern Thailand, with special reference to schistosomiasis.

454 stool specimens were collected from the Laotian refugees residing in the refugee camp, Ubon Province, from August 8 to 11, 1978, and were examined by formalin ether sedimentation technique. One of them (0.22%) was infected with Schistosoma mekongi. Since there are freshwater hydrobiid snails, Lithoglyphopsis aperta, the intermediate host of S. mekongi in that area, it is probable that the disease may become established in Northeastern Thailand in the future, which will eventually lead to health and economic problems in Thailand.


In vitro inhibition of rat uterine contractility induced by 5 alpha and 5 beta progestins.

Ten natural progestins were evaluated for their capacity to inhibit the in vitro motility of rat's uterus. Progestins with their ring A reduced in the 5 beta position were significantly more potent than delta 4-3 keto and 5 alpha reduced progestins. These last progestins were ineffective to inhibit uterine motility excepting 3 alpha-hydroxy-5 alpha-pregnan-20-one which was slightly less effective than progesterone. The potency of the progestins to inhibit uterine motility was related to their capacity to induce membrane stabilization. The data indicates that 5 beta, but not 5 alpha reduction of progesterone, may be important for regulating myometrial activity.


Measurement of the testosterone binding parameters for both testosterone-estradiol binding globulin and albumin in individual serum samples.

This report describes a solid phase method for the characterization of testosterone binding to both albumin and testosterone-estradiol binding globulin (TeBG). TeBG is adsorbed from serum samples onto a solid phase matrix of concanavalin A covalently linked to 4B Sepharose. The binding of testosterone is then examined both in the presence and absence of the endogenous serum albumin. Analysis of the resulting Scatchard plots permits determination of the TeBG binding capacity, TeBG association constant and a parameter of albumin binding equivalent to the product of its affinity and capacity for binding testosterone. Results showed that the TeBG capacity was lower in men than in women (18.4 +/- 5.8 vs. 33.1 +/- 19.2 nM, p less than 0.01). The association constant was greater in men (1.59 +/- 0.35 vs. 1.19 +/- 0.32 x 10(9)M-1, 10(9)M-1, p less than 0.01). There was no difference in the albumin binding parameter (43.8 +/- 18.3 vs. 46.6 +/- 15.5, NS). These parameters can then be used to calculate the distribution of the circulating testosterone into albumin bound, TeBG bound and unbound fractions.


[Daily and seasonal changes in the oviposition activities of Culex pipiens pipiens L. (author's transl)].

The oviposition activity of C. p. pipiens during summer and autumn has been investigated at two breeding sites in West and North Germany. The egg rafts were collected and counted daily or hourly. Soon after its begin oviposition reached a high peak and then decreased sharply and faded out towards sunrise. There was an obvious correlation between the hourly maximum number of egg rafts deposited and nightfall. The peak of oviposition regularly followed the sunset with one hour delay. It shifted with the changing daylight period according to the season and geographic latitude. The decrease and ending of the oviposition in September is considered not to be related to the decreasing temperatures, but to be due to the disappearance of the gonoactive summer generation and the predominance of the diapausing females of the over-wintering population.


[The epidemiological significance of neo-natal parasitism with microfilariae of Onchocerca volvulus (author's transl)].

Between April 1977 and June 1978, 214 babies born of 210 mothers infected with Onchocerciasis, were examined at the maternity of Po Hospital (Upper Volta). In four of them (1.9%) dermal microfilariae of Onchocerca volvulus were found during the first week after birth. In two other cases microfilariae were seen in the tissue of the umbilical cord. All specimens from placentas and amniotic fluid gave negative results. The infected babies were reexamined monthly monthly from 2 to 18 months, depending on the cases. One child remained positive until the 6th month follow-up. The base-line examination of 5.757 children less than 2 years old from different villages in the WHO Onchocerciasis Control Programme in the Volta River Basin Area showed that 1% of children less than one year old and 2% of children of 12 to 23 months old were carriers of dermal microfilariae. These results indicate that in meso- or hyperendemic areas children less than one year old and carriers of microfilariae of Onchocerca volbulus may have been infected in utero. The existence of such cases, in an area of vector control, does not prove a residual vector borne transmission.


Women, doctors, and family health care: some lessons from rural Java.

The following article describes traditional health care systems of rural Indonesian women. It distinguishes the central from the peripheral aspects of systems that women have developed to meet their own needs and contrasts them with modern health care systems. It suggests what can be done to keep the valuable features of each approach.


[Aspects of the development of ocular onchocerciasis in West-Africa after three years of simulium control (authors transl)].

In four rural West-African communities with different degrees of ocular affection the development of ocular onchocerciasis has been evaluated after three years of vector control. In the area of a successful disruption of the transmission the population with a slight degree of ocular onchocerciasis before control operations started, did not show an aggravation of the lesions. In those groups severely affected at the beginning of vector control the lesions showed no progression in the majority of the cases. The diminuition of the ocular parasite load, resulting from the reduced transmission, appears to be an important factor in the change of the incidence of blindness and severe ocular lesions attributable to onchocerciasis. Contrary to this the aggravation of ocular lesions was found to be more severe in a community situated in the area reinvaded by the vector than in those that did not experience a reinvasion of the fly.


The laboratory maintenance and rearing of Simulium damnosum complex species as a research tool for the Onchocerciasis Control Programme in the Vola River Basin.

The laboratory maintenance and rearing of Stimulium damnosum complex species and the cytotaxonomic determination of reared larvae, has been useful to OCP in the following fields of investigation: 1. Species identification of reinvading females. 2. Distribution of biting populations of S. damnosum complex species. 3. Identification of eggs and small larvae found within the OCP area. 4. Host preferences of species within the complex. 5. Vector potential of S. damnosum complex species for Onchocerca volvulus and O. ochengi. 6. Provision of identified material for morphological investigation. The technique of indirect adult identification using reared larvae, may eventually by largely superseded by progress in morphological taxonomy.


The use of the starch grain and phenolsulphonphthalein tests to investigate infertile cows.

The starch grain and phenolsulphonphthalein (PSP) tests were used to investigate the patency of the fallopian tubes in five "repeat breeder" cows. Evidence of tubal lesions was determined in three cows on rectal palpation. Using the starch grain test, bilateral occlusion was determined in three animals, left sided occlusion was determined in one and right sided occlusion in another. Using the PSP test there was evidence of bilateral occlusion in two of the four coes which were tested. In four cows the genital organs were examined visually and by palpation at laparotomy and in two cows tubal occlusion was confirmed when they were flushed with saline, and patency restored. In one animal both ovaries were almost completely encapsulated, while in the fourth adhesions involving the fimbriae occluded the ostia. There were broken down and this cow was the only one which subsequently conceived.


The California Child Health and Development Studies: twenty years of research.

The Child Health and Development Studies are prospective longitudinal studies of pregnancy and delivery, and of health and development of the children from birth until adolescence. The studies are conducted on members of a prepaid medical insurance plan, and reside in the Oakland area of California, USA. The infants were born in one hospital, between 1659 and 1967. A variety of biomedical studies have been published; these have been summarized in separate sections representing the major research projects. Currently, an adolescent study is in progress in which the older children of the study cohort participate.


[Lymphatic vessels in the uterus of aging nulliparous and multiparous mice].

The morphological changes in the uterine lymphatics in aging nulliparous and multiparous mice, as shown by the application of dyestuffs (patient blue violet and Japan ink) are described, and their appearance corresponds to that described in earlier papiers by Fabian (1976, 1977, 1978). It is apparent on the basis of these findings that with the cessation of the sexual cycle, the previous regularly repeated morphological changes in the mouses uterus move into another stage, and associated with this the lymphatics inevitably take part in the aging process. According to Lindner (1975) this is essentially a dynamic process, rather than one which is purely passive, dengerative or involutional.


Persistent measles virus infection in a calf kidney cell line. Note III. Cellular alterations in the selected chronically infected K-2 cell line.

Marked morphological, growth and chromosome alterations pointing to in vitro cellular transformation were made evident in a selected calf kidney cell line (K-2) chronically infected with measles virus. The transformed cell line released infectant virus and had no oncogenic potential for the hamster.


Benzo(a)pyrene contents of meat products.

The Benzo(a)pyrene contents of 386 smoked and 18 grilled meat products were determined by application of capillary gas-chromatography-mass fragmentography using inner standards. 82 per cent of 183 black smoked hams contained appreciably more than the legal maximum amount of 1 ppb. The quantities of BaP increased very much with increase of soot accumulation on the surface. Only 15 per cent of 95 hams and only 9 per cent of 87 sausages smoked by normal methods had excessive BaP content. The amounts in excess of 1 ppb were much lower in these hams. Bratwurst grilled by use of pine-cones, spruce-cones and hard wood contained on average 28 ppb BaP. The BaP amounts of Bratwurst grilled over charcoal were without exception lower than 1 ppb.


[Are television cameramen and sound operators overstressed?].

Sickness absences occurred between 1975 and 1977 among 29 cameramen and sound operators of the Swiss Television Corporation (in French language) in charge of outside reports have been compared with both those of a control group working in TV studio and with those of the staff of the Federal Administration. No significant difference was found between these three groups as regards absences for illnesses and injuries lasting one to three days and for injuries lasting more than three days. On the other hand, illnesses of more than three days were significantly more frequent among the cameramen and sound operators. This was mainly due to a very high rate of psychosomatic diseases and nervous breakdown. This difference has been attributed rather to professional fag than to attraction to these professions of more vulnerable people.


[Hemolytic crisis in nocturnal paroxysmal hemoglobinuria after ingestion of acetic acid].

In a female patient with paroxysmal nocturnal haemoglobinuria a dramatic haemolytic crisis developed after ingestion of acetic acid. The pathogenesis of the disease, therapeutic possibilities and possible mechanism of haemolysis are discussed.


Position of ultimobranchial body cysts in the human fetal thyroid gland.

In a series of 21 human fetal thyroid glands examined histologically in serial sections, seven ultimobranchial body cysts were found. The position of these cysts correlated well with the distribution of calcitonin-containing cells found by previous investigators in the adult thyroid gland. Ultimobranchial body cysts found external to the thyroid lobes may offer a developmental explanation for the paucity of calcitonin found in some adult thyroid glands. The close developmental relationship between the parathyroid gland and the ultimobranchial body could explain the presence of calcitonin found in these glands in some adults.


Inhibition of intestinal smooth muscle contraction by surface-active alkyltrimethylammonium salts.

The effects of surface-active alkyltrimethylammonium salts (C10--C20) on the contractile activity of isolated rat jejunum and on the gastrointestinal motility in anaesthetized rats were studied. The surfactants caused a dose-dependent depression of spontaneous contractions and of acetyl-beta-methylcholine and BaCl2 induced contractions of isolated rat jejunum. The depressant activity of the surface-active alkyltrimethylammonium salts on smooth muscle contraction increased with an increase in the length of the alkyl chain to maximum activity at C16. It is suggested that the depressant activity of the surface-active alkyltrimethylammonium salts on smooth muscle contraction is due to a non-specific interaction of the surfactants with the cellmembrane of the muscle cells. No effect on gastric and intestinal motility in vivo was observed following intragastric or intraintestinal administrations of surface-active alkyltrimethylammonium salts. This lack of effect upon intraintestinal or intragastric administration probably depends on an inability of the surfactants to reach the site of action when administered from the mucosal side.


Regional cerebral blood flow and visual attention in the awake isolated cerebrium of the pretrigeminal cat.

The effect of visual stimulation on cerebral blood flow (CBF) was studied in five cats with brainstem transection at the pretrigeminal level. The CBF was measured in the occipital and frontal cortex by external monitoring of the clearance of 133Xe. As a visual stimulus, a feather duster moving for 2 min in front of the cats eyes was used. This stimulus evoked an increase of CBF. In the occipital cortex the CBF increase was greater and comparable to that evoked by elevation of the arterial pCO2. Both in the occipital and frontal cortex the CBF response was positively correlated with the intensity of the ocular-following reflex and the cortical EEG arousal. It is concluded that the CBF increase was correlated with the degree of attention paid by the cat to the visual stimulus.


Brief clinical report: the Dubowitz syndrome in a teenager.

The Dubowitz syndrome has been recognized during the past few years as a new, distinct intrauterine growth-retardation syndrome with autosomal recessive inheritance. One new patient is presented, a 10 1/2-year-old slightly mentally retarded girl.


Complete androgen insensitivity with a normal amount of 5 alpha-dihydrotestosterone-binding activity in labium majus skin fibroblasts.

We have studied labium majus skin fibroblast strains from six unrelated, previously unreported, patients with complete androgen insensitivity (CAI). Four have markedly reduced specific 5 alpha-dihydrotestosterone-binding (DHT-binding) activity (receptor-negative). The other two (receptor-positive) have normal activities in whole-cell homogenates, the 100,000g supernatant of cell sonicates prepared in 0.4 MKCl, purified whole nuclei, and the nuclear fraction that resists extraction with 0.4 MKCl. In one of the two, the DHT-binding macromolecules in the cytosol and 0.4 M KCl-extractable nuclear fraction have normal molecular sieving profiles and binding activities. One of the receptor-positive patients has maternally related affected relatives in three successive genetations. Appreciable unexplained interexperimental variation of the DHT-binding activities in genital skin fibroblast strains demands that multiple assays be performed on a strain before its receptor status is classified quantitatively. In our experience to date with genital skin fibroblasts, four of 13 propositi with CAI have been receptor-positive.


[Contribution to the definition of reference values in the hare: hematology -- blood biochemistry (author's transl)].

The following hematological and biochemical reference values were determined in 150 hares: hematocrit, blood count and leucocytic formula, Na, K, Cl, P, Ca, Mg, Cu, Zn, glucose, urea, creatinine, uric acid, cholesterol, bilirubin, triglycerides, proteins and fractions, PAL, PAC, TGO, TGP, amylase, GGT, LDH. Once the effects of sex and age have been established, the references defined here will be used as a base for interpreting disturbances linked either to pathology or nutrition.


[Binding capacity of testosterone estradiol binding globulin (TeBG) in normal children and in children with endocrine pathology].

The binding capacity of plasma TeBG was measured by polyacrylamide gel electrophoresis. In normal prepubertal children the values are identical in the two sexes boys (6.23 +/- 1.72 microgram/dl); girls (6.21 +/- 1.93 microgram/dl). In boys puberty induces an immediate and highly significant (p less than 0.001) drop in TeBG (1.79 +/- 0.75 microgram/dl) while it remains unchanged in girls (5.34 +/- 0.92 microgram/dl). In newborn males there is a physiological rise in plasma testosterone in the first months of life with a parallel rise in TeBG. In boys with precocious puberty the drop in TeBG is delayed in comparison to the rise in plasma testosterone. The pubertal drop of TeBG is delayed and incomplete in boys with male pseudohermaphroditism. The data indicates that the measurement of TeBG binding capacity can be used as an indirect method to evaluate the peripheral effect of testosterone. The lack of effect of HCG on TeBG means that this test is of no value as a functional assessment of prepubertal subjects.


Effect of human plasma apolipoproteins on the activity of purified lecithin: cholesterol acyltransferase.

An active preparation of lecithin: cholesterol acyltransferase (LCAT, EC 2.3.1.43) was isolated from human plasma by density ultracentrifugation, high-density lipoprotein affinity chromatography, DEAE-Sepharose and hydroxylapatite chromatography. This enzyme preparation gave a single band on polyacrylamide gel electrophoresis in 8 M urea and on sodium dodecyl sulfate gel electrophoresis. Upon analytical isoelectric focusing the enzyme separated into at least five isoforms with isoelectric points ranging from 5.1 to 5.5. The enzyme with an apparent molecular weight of 66,000 +/- 2,000 was characterized by a high content of glutamic acid, aspartic acid, leucine and glycine and contained approximately 31 moles of glucosamine/10(3) moles of protein and no galactosamine. The purified enzyme, stored at 20-40 microgram/ml at 4 degrees C, had a half-life of 26 +/- 4 days. The effect of purified human plasma apolipoproteins A-I, A-II, C-I, C-II, C-III and D on the activity of purified LCAT was studied, using egg-yolk lecithin (40 microM): cholesterol (10 microM) vesicles prepared in 1.25% ethanol in the absence or presence of 0.5% albumin. Addition of albumin to the incubation mixture nearly doubled the esterification rate of LCAT with A-I as activator (n=4), whereas it inhibited esterification by approximately 35% (n=3) if C-I was the activator. Maximum activation by C-I yielded only 13 +/- 6% (vesicles with albumin) or 42 +/- 5% (vesicles without albumin) of the LCAT activity obtained with A-I. Each of the apoproteins A-II, C-II, C-III and D inhibited the LCAT reaction in the presence of A-I or C-I at concentrations needed for maximal activation. Contrary to previous work, apolipoprotein D does not appear to be an activator of LCAT. LCAT activity is significantly affected by albumin and the apolipoproteins A-II, C-II, C-III, and D.


[Freshwater snails and vectors of schistosomiasis mansoni in Martinique (French West Indies)].

An inventory of the freshwater Molluscs in Martinique was worked out during 1972 to 1978. Each of the 19 species is shown with its main characteristics. The distribution of Biomphalaria glabrata and Biompharia straminea was studied. The epidemiological importance of these two snails is discussed.


Measurement of endothelial fibrinolytic activity in aorta and vena cava in rabbits: a fibrin-agar plate method.

The fibrin-agar plate method was used to estimate fibrinolytic activity from the luminal surfaces of aorta and vena cava with or without denudation of endothelium in rabbits. Diffuse endothelial denudation was accomplished by air-dry injury to the luminal surfaces for 24 hours prior to sacrifice. The segments individually obtained from the aorta and vena cava were immediately turned inside out in a cylindrical fashion and soaked in a vial containing plasminogen-rich solution. The vials were kept in a refrigerator at 4 degrees C for 4 hours. Five microliter of the solution was dropped on a fibrin-agar plate containing 0.08% fibrinogen (plasminogen free) and 1.4% agar in 0.01 M phosphate buffer with a pH of 7.4. A thrombin solution was then added to the plates, which were incubated for 18 hours at 37 degrees C in a moist chamber. The fibrinolytically digested areas revealed no comparative difference in fibrinolytic activity between the aorta and the vena cava either in the experimental or control group. However, a plasminogen activator was detected on the luminal surfaces of both the aorta and the vena cava with endothelial denudation as well as in normal controls. These results suggest that luminal fibrinolytic activity may be located not only in endothelial cells but possibly in other sources as well. Further examination of the interaction between the tissue activator and the inhibitor and determination of their localization are needed. Thrombogenesis may be an important factor in atherogenesis; in certain circumstances, detachment of the endothelial cells exposes underlying collagen fibrils and subsequently initiates the aggregation of platelets and cellular proliferation in the intima. There are, however, many unresolved questions concerning the precise mechanisms of development, resolution and organization of thrombi.


[Specialization of the ovocytic endoplasmic reticulum near the contact of the hind gut in Trichinella spiralis (author's transl)].

In Trichinella spiralis, the bigger ovocytes show contacts with the cuticula of the hind gut. Near these contacts, the ovocytic endoplasmic reticulum is hypertrophied. This device is described with details and compared to that one of the stichocytes; its possible role is discussed.


Depressed incidence of oestrus in ewes with clover disease at the beginning of the breeding season.

The incidence of oestrus was depressed in ewes with permanent clover infertility running on non-oestrogenic pasture, particularly in the first part of the breeding season. The depression was due to the failure of some ewes to display oestrus, and to a more erratic pattern of oestrous activity in the other ewes. The incidence of oestrus was restored to normal by treatment with progesterone. In contrast, the incidence of oestrus was reduced in affected ewes grazing in oestrogenic pasture.


Isolation and characterization of binding proteins for retinol from the cytosol, nucleosol and chromatin of the oviduct magnum of laying hens.

Protein fractions that bind retinol were isolated from the cytosol, nucleosol and chromatin of the oviduct magnum of laying hens. The proteins isolated from the three sources showed similar elution profiles on chromatography through Sephadex G-75 and G-50 columns, and comparable mobility during electrophoresis on sodium dodecyl sulphate/polyacrylamide gels. Their molecular weights were calculated to be around 14500. When oviducts from vitamin A-depleted and vitamin A-repleted immature chicks given oestrogen injections for 6 consecutive days were incubated with [3H]retinyl acetate, uptake of the radioactivity in the nuclei of the vitamin A-depleted tissue was severalfold higher than that in the nuclei from the vitamin A-repleted tissue.


A study of the copper-binding proteins in liver and kidney tissue of neonatal normal and mottled mutant mice.

The Cu2+-binding proteins from liver and kidney tissue of 7--8-day-old brindled (Mobr) mice and their normal littermates were compared. (1) Separation over Bio-Gel P-10 showed that the differences in the Cu2+ content of mutant tissues were largely associated with a low-molecular-weight protein fraction (mol.wt. 14 500). (2) Further purification of this low-molecular-weight fraction by anion-exchange chromatography revealed four subfractions. The Cu2+ content of each subfraction reflected the Cu2+ status of the tissue of origin; the Cu2+ contents of the mutant kidney subfractions were elevated and those of the mutant liver were depressed compared with normal. In contrast, the protein contents of the subfractions were less variable and did not reflect the differing Cu2+ contents. (3) Amino acid analysis of the four subfractions from CuCl2-treated mutant and normal animals revealed clos similarities. The proteins showed high glycine, glutamic acid, serine, alanine and lysine contents and a rather variable cysteine content. Differences were apparent in the normal liver subfractions, which showed a higher cysteine content and lower glutamic acid content than did either the mutant liver or normal and mutant kidney subfractions. These observations, together with the recorded presence of aromatic amino acids, indicated that these proteins are not thioneins.


Effects of manganese ions and magnesium ions on the activity of soya-bean ribulose bisphosphate carboxylase/oxygenase.

The Michaelis constants of soya-bean ribulose bisphosphate carboxylase for CO2 in the carboxylation reaction and for O2 in the oxygenation reaction depend on the nature of the bivalent cation present. In the presence of Mg2+ the Km for bicarbonate is 2.48 mM, and the Km for O2 is 37% (gas-phase concentration). With Mn2+ the values decrease to 0.85 mM and 1.7% respectively. For the carboxylation reaction Vmax. was 1.7 mumol/min per mg of protein with Mg2+ but only 0.29 mumol/min per mg of protein with Mn2+. For the oxygenation reaction, Vmax. values were 0.61 and 0.29 mumol/min per mg of protein respectively with Mg2+ and Mn2+.


Synthesis and chemical properties of N- and O-phosphorylated derivatives of creatinol.

N-Methyl-N-(beta-hydroxyethyl)-guanidine O-phosphate (creatinol O-phosphate) was synthesized from creatinol by phosphorylation with partially hydrolyzed phosphoryl chloride or by dehydration of its phosphate salt. Creatinol N-phosphate was obtained by addition of N-methylamino ethanol to bis-p-nitrobenzylphosphocyanamide, followed by hydrogenolysis. The chemical properties of both compounds were investigated; creatinol N-phosphate was rearranged to creatinol O-phosphate by heating.


Acute clinical tolerance of creatinol O-phosphate.

Acute clinical tolerance to N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was investigated in volunteer human subjects without heart or renal disease and without other serious illness. COP was administered i.v. at three different dosages, 1020 mg (group A), 2040 mg (group B) and 3060 mg (group C), in comparison with a placebo (group D). Arterial pressure, heart rate, ECG pattern and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups B and C. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule and the increase in diuresis from a simple osmotic process required to dilute the phosphate in the tubular fluid. All these alterations were statistically significant and dose-related with COP and had been expected. COP proved to be a very well tolerated drug without any evident side effect.


An analysis of the reduction by creatinol O-phosphate of the myocardial lesions evoked by isoprenaline in the rat.

The distribution and the size of lesions evoked in rat heart by the injection of isoprenaline 30 mg/kg have been estimated in rat pretreated or not by various dosages of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate). It has been observed that the number of lesions was inequally distributed in the various parts of the heart. Creatinol O-phosphate pretreatment reduced both the number and the size of the reactive areas. The reduction of the number of foci was dose-dependent. The action of the lowest creatinol O-phosphate doses was increased by a pretreatment during 4 days instead of the 4 h pretreatment initially used. The size of the reactive area was also reduced but in a manner indicating an action of large creatinol O-phosphate dosages on the microcirculation. It is concluded that, due to its protective action against cardionecrosis, creatinol O-phosphate has great potential value in patients with myocardial infarction in whom the extent of the infarct size may be limited by an action on the jeopardized area.


The action of creatinol 0-phosphate on the inotropic effect of isoprenaline in isolated rat atria and in anesthetized dogs.

The action of N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate) was studied on the contractility of the heart, in vitro on isolated rat atria and in vivo in anesthetized dogs. Creatinol O-phosphate was without action on the contractility of isolated rat atria stimulated by isoprenaline 10(-8) mol/l which produced the maximum inotropic effect. Creatinol O-phosphate increased the contractility evoked by isoprenaline 10(-5) mol/l and impaired the development of the negative inotropic effect evoked by prolonged treatment with this large dose. In dogs, creatinol O-phosphate pretreatment increased the positive inotropic effect of large but not low isoprenaline dosages. It is concluded that creatinol O-phosphate increased the contractile efficiency of the heart submitted to the action of an excess of catecholamines.


Ionic changes evoked by isoprenaline in rat hearts in vivo and in vitro and their reduction by creatinol O-phosphate.

The action of large doses of catecholamines on the Ca and Mg content of rat heart has been examined both in vivo and in vitro. It was observed that the ionic changes evoked in vitro by isoprenaline 10(-5) mol/l were similar to those evoked in vivo by isoprenaline 30 mg/kg and that both were reduced by N-methyl-N-(beta-hydroxy-ethyl)guanidine O-phosphate (creatinol O-phosphate) in a dose-dependent manner. ED50 was equal to 3 x 10(-7) mol/l. These results indicate that the cardionecrotic action evoked in vivo by isoprenaline and its reduction by creatinol O-phosphate may be attributed to a direct action on the myocardial cell.


Protective action of creatinol O-phosphate against serum CPK activity enhanced by isoprenaline in the rat.

Isoprenaline (ISP) in the rat (500 mg/kg s.c.) was shown to be able to enhance the creatin phosphokinase activity (CPK) in serum from 135 U/l in the control animals to about 600 U/l in 5 h, i.e. at the peak. When the rats were pretreated with N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP), the CPK enhancement was reduced to an extent related to the doses of COP (250, 500 and 1000 mg/kg i.p.). COP protection was about 16% with the lower dose but increased to 50% with the highest dose according to linear regression (COP doses versus CPK levels, p less than 0.01). The protective action against serum CPK enhancement evoked by ISP is common to other classes of drugs, such as beta-blocking agents, calcium antagonists and corticosteroids. In the case of COP and calcium antagonists a common mechanism, which has the effect or reducing myocardial calcium overload due to ISP, may be assumed on the basis of other previous investigations on the ion balance across the heart cell membrane and on the uptake and subcellular distribution of COP in the isolated perfused rat heart.


Protective effect of creatinol O-phosphate (COP) on ventricular fibrillation and death induced by intravenous CaCl2 in mice.

The activity of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) on the acute toxicity of CaCl2 in mice was studied. The results obtained in the present investigation show that COP administered i.v. is able to antagonize, in a dose-dependent way, the lethal ventricular fibrillation provoked by CaCl2 in unanesthetized mice. Prenalamine and cinnarizine, two calcium antagonistic compounds, proved to be active in a way qualitatively similar to COP.


Protective effect of creatinol O-phosphate (COP) on some experimental arrhythmias in vitro and in vivo.

The activity of N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate (creatinol O-phosphate, COP) on two in vitro and in vivo experimental arrhythmias was investigated. The substance proved to be active in delaying the onset time of aconitine induced arrhythmias in guinea-pig atria. COP showed also a definite antagonizing activity against chloroform-induced ventricular fibrillation in mice.


Effects of creatinol O-phosphate on serum enzymes in acute myocardial infarction.

Two groups of 23 patients, each with acute myocardial infarction, were treated. The first group (control) received glucose-insuline-K+ (GIK) over a 3-day period, and the second GIK and N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) (3.06 g i.v./24 h), again for a 3-day period. The six enzymes investigated, i. e. GOT, GPT, LDH, HBDH, CK and MBCK, all decreased between 33 and 49% in the COP group as compared with the control group, reaching a degree of statistical significance of less than 0.01. The decrease in these enzymes was attributed to the protective action of COP on the cell membrane permeability, in agreement with a series of previous papers.


Preliminary report on electrophysiological effectiveness of creatinol O-phosphate (COP) in human subjects.

N-Methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP), in previous pharmacological and clinical research showed useful effects on both normal and ischemic heart. These effects can be reconduced to a protective action of COP on cell membrane. In this investigation the possible electrophysiological effects of COP were ascertained in 6 patients, some of whom were free of excitation-conduction disturbances, while others were suffering from sinusal automaticity of A-V conduction alterations. When the nodal A-V conduction was slowed by iatrogenic or functional factors, COP as well as atropine improved it. Thus both COP and atropine act in the non-organic component of the conduction disturbances. The organic component was not affected by both the drugs. The effect of atropine was more evident than that of COP. All the electrophysiological parameters were not affected by COP. This fact allows COP to be administered with absolute safety even in the presence of alterations in the formation and conduction of the stimuli.


[Effect of emotional-pain stress on the contractile function and sensitivity to noradrenaline of cardiac muscle].

The effect of variations in the Ca concentration in the perfusate on the function of isolated hearts of control rats and of those who sustained the emotional-pain stress (EPS) was studied. It was found that the EPS sharply increased the cardiac response in the animals to shifts in the Ca concentration. A rise in the main parameters of the cardiac contractile function in response to an increased Ca concentration was more pronounced in rats after the EPS than in the controls. The sensitivity to noradrenaline decreased 2-fold as compared to the control animals. It is suggested that the growth of the relationship between the cardiac function and the Ca concentration in the animals after the EPS is caused by the damaged membranous mechanisms of Ca transport in the myocardial cells.


Purification of a basic somatomedin, from human plasma Cohn fraction IV-1, with physicochemical and radioimmunoassay similarity to somatomedin-C and insulin-like growth factor.

A basic somatomedin (SM) was purified from human plasma Cohn fraction IV-1 using an initial acid--ethanol--acetone extraction procedure followed by alternating molecular size or charge protein separation techniques. The final recovery of SM bioactivity was approximately 2% of that present in the starting Cohn fraction. The purified SM has an approximate molecular weight of 7500, pI 8.6, 4000 SM bioactivity units per milligram (as measured by a hypophysectomized rat bioassay) and a parallel approximately equipotent radioimmunoassay dose--response curve to SM-C and insulin-like growth factor-1 (IGF-I). Sodium dodecyl sulfate--polyacrylamide gel electrophoresis of this purified SM revealed a single protein band. The preliminary determination of the amino acid sequence of the N terminus suggested that this SM preparation was over 75% pure and the first five N-terminal amino acids were identical with those of IGF-I.


A modified pork plasma agar for the enumeration of Staphylococcus aureus in foods.

The coagulase reaction of Staphylococcus aureus on the PPSA (pork plasma for S. aureus) agar of Devoyod et al. was found to be fibrinogen-deficient. By including bovine fibrinogen (BFG) in the medium, the fibrin halos around S. aureus colonies became more distinct, preparations of pork plasma previously unacceptable for inclusion in the original PPSA agar were performing well, and the amount of pork plasma required in PPSA agar could be reduced by nearly 90%. In the modified medium, designated PPF (pork plasma fibrinogen) agar, the agar base (Baird-Parker agar without egg yolk) was unchanged. After surface plating, the base was covered with 8 mL of a modified overpour agar: 2.5% pork plasma, 0.38% BFG, and 0.0015% soy trypsin inhibitor in 0.7% Bacto agar. Most S. aureus strains could be enumerated after 24 h of incubation at 35 degrees C; the others required 44 h. Without soy trypsin inhibitor, a number of strains showed considerable fibrinolysis between 24 and 44 h of growth; this activity was neutralized by the inhibitor. The S. aureus counts of 27 food samples on PPF agar were essentially the same as the confirmed S. aureus counts obtained by the Baird-Parker method.


Effect of a single dose of glucocorticoid on the diurnal variations of TSH, thyroxine, 3,5,3'-triiodothyronine, 3,3'5'-triiodothyronine and cortisol in normal men.

Plasma thyrotropin (TSH) and cortisol concentrations were suppressed immediately after an intravenous bolus dose of 8 mg betamethasone in 6 male subjects. The circadian variations of these hormones disappeared for 40 hr (TSH) and 44 hr (cortisol). Plasma thyroxine (T4), 3, 5, 3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) levels did not show diurnal variations before betamethasone administration. Plasma T3 levels decreased to 66% of the basal levels 20 hr after batamethasone administration, whereas plasma reverse T3 levels increased to 163% of the basal levels at 24 hr. These changes were reversed by 3 to 5 days after betamethasone. The earlier recovery of the diurnal rhythm of TSH than that of cortisol suggests that the TSH rhythm is not under the direct control of circulating cortisol.