Biomedical subjects
Publications and source records attributed to S Daya.
Wistar rats show a circadian variation in their response to stress. Pinealectomy exacerbates stress-induced gastric ulceration in rats. This effect is counteracted by melatonin administration.
When rats were exposed to extended light into the normal dark phase, the administration of 5-aminolevulinic acid (5-ALA) markedly stimulated the accumulation of tryptophan (TRP) and the synthesis of serotonin (5-HT) in the forebrain. When a single injection of melatonin (25 micrograms) was given near the end of the 5-ALA treatment, the rise in forebrain TRP levels was either totally prevented or reversed; likewise, the increased levels of 5-HT were also suppressed. Melatonin by itself also slightly suppressed forebrain TRP levels in non-5-ALA-treated rats. Whether these are pharmacological or physiological effects of melatonin remains to be determined.
Fluorimetry and spectrophotometry have been used to study the binding of dimethyl, dipropyl, dibutyl and diphenylnitrosamine to nicotinic acetylcholine receptor isolated, and purified, from Torpedo fuscomaculata. Scatchard analysis indicates that all four ligands are true agonists of the receptor exhibiting positive cooperative binding with the existence of more than one class of binding site. The number of binding sites for the nitrosamines approximates 2. Diphenylnitrosamine binds to the receptor more tightly at low concentrations (Kd1 = 1.3 microM) than the aliphatic nitrosamine (Kd1 = 8-12 microM). Yet at high concentrations all nitrosamines behaved with similar Kd values (27-38 microM).
Prior melatonin administration (1,5 and 10 mg/kg b. wt) causes a significant reduction in gastric ulceration induced in male rats by restraint immobilization in the presence of low temperatures.
An attempt was made to use the pineal gland as a model for the study of the primary mode of action of alpha-methyldopa, which is still unclear. Organ cultures of pineal glands from rats treated chronically with alpha-methyldopa showed enhanced conversion of radio-active serotonin to melatonin (aMT) as well as its precursor, N-acetyl-serotonin (aHT). This treatment was also found to raise serotonin-N-acetyltransferase (NAT) activity. These increases associated with alpha-methyldopa treatment were further enhanced by the beta-adrenergic agonist, isoproterenol, suggesting a supersensitivity-type effect occurring at the level of the beta-receptor. A subsequent binding study, however, showed a decrease in beta-receptor binding with exposure to alpha-methyldopa, providing mitigating evidence against the occurrence of a supersensitivity phenomenon. It is possible that a metabolite of alpha-methyldopa acts as an alpha 1 and beta-agonist, resulting in greater melatonin (aMT) and N-acetylserotonin (aHT) synthesis than by a beta-agonist, isoproterenol.
Intracranial complications of frontal sinusitis, although rare today, do still develop despite widespread use of antibiotics. We report a case which demonstrates how silently a frontal lobe abscess may present with subtle changes in mood and behaviour, with no focal neurological signs. Diagnosis and management are discussed and a brief review of the incidence of intracranial complications of frontal sinusitis, mode of spread, clinical presentation, investigations, treatment and bacteriology is presented.
Since multiple ovarian punctures are performed during oocyte retrieval, the likelihood of blood contaminating the follicular fluid is high. The purpose of this study was to determine whether the presence of blood clots, which are frequently seen in the cumulus of oocytes retrieved under ultrasound guidance, has any effect on fertilization and subsequent embryo cleavage and to identify oocyte characteristics which may predict these events. Oocytes were morphologically graded and the presence of blood clots in the cumulus was recorded. Cases in which the male partner had a total motile sperm count less than 20 x 10(6) on the day of insemination were excluded from the logistic regression analysis. The presence of blood clots in the cumulus was a negative predictor of cleavage [odds ratio (OR) = 0.54]. The results indicate that an oocyte with optimal quality is one which is spherical (OR = 5.45), has an expanded corona (OR = 3.80) and has no blood clots in the cumulus complex.
A naturally occurring compound, 6-methoxybenzoxazolinone (6-MBOA), present in grasses, has been shown to induce sexual maturation in a number of rodent species. The structural similarity of 6-MBOA and melatonin has led researchers to suspect that 6-MBOA might induce its progonadal effects by directly altering pineal function. Previous studies have shown that 6-MBOA has the properties of a weak beta-adrenergic agonist capable of stimulating rat pineal N-acetyltransferase (NAT) activity at pharmacological concentrations of 10(-3) M. In the present study we have examined the effect of 6-MBOA on both the pineal melatonin synthesizing enzymes, namely, NAT and hydroxyindole-O-methyltransferase (HIOMT) as well as on melatonin production, in organ cultured rat pineal glands. In addition, we have also examined the ability of 6-MBOA to displace a ligand from rat brain alpha- and beta-adrenoceptors. Our results confirm that 6-MBOA stimulates NAT activity and melatonin production at the high concentration of 10(-3) M. It appears to have no effect on HIOMT activity. A competition study shows that 6-MBOA is able of displacing ligands at the alpha- and beta-adrenoceptors but only at concentrations greater than 10(-4) M. Whether such high concentrations of 6-MBOA reach the pineal of rodent in their natural habitat is unknown. However, if 6-MBOA does mediate progonadal effects by altering pineal function it would be expected that 6-MBOA would ultimately inhibit the effects of melatonin. The possibilities are that the high melatonin levels induced by 6-MBOA cause desensitization of melatonin receptors or that 6-MBOA is an antagonist at the level of the melatonin receptor, thus restricting the inhibitory effects of melatonin on the reproductive system.
Suppressor activity in in vitro fertilization (IVF) culture medium correlates with successful implantation. High performance liquid chromatography fractionation revealed peak(s) of inhibitory activity in the 1,000- to 5,000-Da molecular weight range. Inhibitory activity was dependent on the presence of fetal bovine serum (FBS) and was abrogated both by heat treatment of the serum and by pretreatment with monoamine oxidase inhibitors. Spermine becomes toxic when oxidized by monoamine oxidase to spermine dialdehyde or acrolein. Spermine also shows suppressive activity in the same molecular weight range as IVF supernatants. These data suggest IVF-associated inhibitory activity may be attributable to oxidation of a polyamine, possibly spermine, by monoamine oxidase in FBS. The biological significance is discussed.
The daytime administration of the heme precursor 5-aminolevulinate (5-ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5-ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin-forming enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). 5-ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5-ALA. Although 5-ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.
The supernatants from cultured human oocytes fertilized in vitro contain low molecular weight factors that can suppress or stimulate the proliferative response of lymphocytes in vitro. The inhibitory and stimulatory effects are nonspecific and may be detected using cultured human or murine tumor cell lines. Using such a bioassay, we previously tested fetal cord serum-supplemented culture supernatant and found that an absence of suppression was correlated with an absence of subsequent pregnancy. To test this association further, additional samples were obtained from four different in vitro fertilization (IVF) units and studied blindly without knowledge of the pregnancy outcome. In this series, samples were obtained after the first 12-24 hr of sperm-oocyte incubation and all of the supernatants were from individual embryo cultures. The average number of preembryos transferred to those achieving pregnancy did not differ significantly from the number transferred to those not achieving pregnancy but the level of suppression was greater (8.7 +/- 1.9%) in those becoming pregnant compared to those not achieving pregnancy (0.8 +/- 1.5%). Twenty-two of 61 patients who received at least one embryo with a suppressive supernatant achieved pregnancy, whereas 0 of 19 patients received embryos lacking suppressive supernatants became pregnant. Two patients who received a single embryo from cultures with suppression became pregnant. Several problems with the bioassay method were defined. The culture medium in this series was always supplemented with adult serum, usually from the patient herself, and this serum could be suppressive.(ABSTRACT TRUNCATED AT 250 WORDS)
In vitro fertilization treatment for male infertility is not very successful because fertilization is known to be affected by semen quality. Information on fertilizing ability may provide prognostic information for couples contemplating such treatment. The purpose of this study was to identify semen variables that would predict fertilization and embryo cleavage. Sperm was prepared by the swim-up method before insemination of oocytes obtained by laparoscopy after ovulation induction. Routine semen analysis and the hypoosmotic swelling test for assessment of sperm membrane integrity were performed on aliquots of prepared sperm. Logistic regression and receiver-operator characteristic curve analyses were performed to determine the overall best-fitting model and discriminatory level of variables that would predict cleavage. The results indicate that after the swim-up procedure, at least 10 million sperm/ml, capable of undergoing swelling in hypoosmotic medium, are necessary to increase the likelihood of in vitro fertilization and cleavage.
Inadequate production of progesterone by the corpus luteum results in luteal phase deficiency, which is a frequent cause of recurrent spontaneous abortion. The diagnosis is made by assessment of endometrial biopsy specimens. Measurement of serum progesterone offers a less invasive alternative, but its utility as a diagnostic test is limited since there is no agreement on the level that will accurately differentiate between normal and luteal phase deficiency cycles. The purpose of this study was to determine whether there was an optimal time in the menstrual cycle when serum progesterone measurement could improve the diagnostic accuracy of the test. The results demonstrate that this time period is day 25 to day 26 and not the midluteal phase as has previously been suggested. The discriminatory level was found to be 21 nmol/L and provided a test with sensitivity of 81% and specificity of 73%.
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Progesterone appears to be necessary to support an early pregnancy, and it has been used for this purpose for several decades. Its potential role in women with recurrent miscarriage due to luteal phase deficiency has been suggested, but its efficacy has not yet been demonstrated. Three controlled trials of progesterone treatment in women with recurrent miscarriage have shown small, but not statistically significant, increases in the rates of pregnancies that continue beyond 20 weeks in the treated groups. None of these studies had sufficient statistical power to detect a clinically significant improvement in outcome but pooling the results of these studies using the principles of meta-analysis has allowed an overall effect of treatment to be calculated. The resulting odds ratio for pregnancies reaching at least 20 weeks gestation was 3.09 (95% CI 1.28 to 7.42) which indicates that there is evidence to support the suggestion that progesterone given in early pregnancy is useful in women with recurrent miscarriage. Although, before progesterone is used in this way its efficacy in women with recurrent miscarriage due to luteal phase deficiency must be assessed in prospective double-blind randomized controlled trials mounted in the light of the results of this meta-analysis.
First trimester (10-12 weeks gestation) human decidua contains small lymphocytic suppressor cells that release 22 and 43 kd soluble suppressor factors blocking the action of interleukin 2. Luteal phase endometrium, in contrast, contains large suppressor cells that do not release soluble immunosuppressive factors. However, if luteal phase endometrium from days 24 to 25 of the menstrual cycle is incubated with placental syncytiotrophoblast membrane vesicles, suppressor factors having the same molecular weight as those found in end of first-trimester pregnancy decidua are released into the supernatant. This generation of soluble suppressor activity is dependent on cells similar in size to the small lymphocytic suppressor cell population. When uterine decidua is obtained from women with tubal ectopic pregnancy (early in the first trimester), the decidual tissue releases soluble immunosuppressive factors with a 100-135 kd molecular mass and the suppressor cells are large rather than small in size. Supernatant conditioned by trophoblast dissected from ectopic implants was able to interact with large cells in luteal phase endometrium to generate additional soluble suppressor activity. A model is proposed wherein fetal trophoblast activates two suppressor cell populations (large and small) in endometrium via soluble long-range inducer and by direct contact with trophoblast membrane. The potential role of trophoblast-dependent suppressor cells in preventing rejection of the conceptus leading to occult or clinical abortion is discussed.
Although the clinical diagnosis of appendicitis in pregnancy seems to be complicated by the physiologic changes of pregnancy, evidence from controlled studies is lacking. The aims of this study were to determine whether there are any features of appendicitis in pregnant women that would help to establish the diagnosis and whether any difference exists between the presentation of appendicitis in pregnant and nonpregnant women. Twenty-eight pregnant women with a clinical diagnosis of appendicitis were compared with an equal number of nonpregnant patients matched for age and randomly selected from a group of patients who had appendicitis. No differences were observed in the presenting symptoms, physical signs and laboratory tests. The false-positive rates were identical. The results indicated that the diagnosis of appendicitis is no more difficult in the pregnant state than in the nonpregnant state.
The existence of luteal phase defect has been the focus of much debate, mainly because of inconsistencies in its diagnosis and management. This study was performed to compare progesterone profiles in women with luteal phase defect with those of women with normal cycles and to establish a discriminatory level of serum progesterone that may aid in the diagnosis of this condition. Compared with patients with luteal phase defect cycles, women with normal cycles produced significantly more progesterone in the luteal phase. The serum progesterone level (less than or equal to 21 nmol/L) was the optimal discriminatory level between luteal phase defect and normal cycles and provided a diagnostic test with 70% sensitivity and 71% specificity. In women with recurrent abortion, the incidence of luteal phase defect was 40%, but with treatment 81% of pregnancies were successful. The findings in this study support the existence of luteal phase defect as a clinically significant entity in recurrent first-trimester spontaneous abortion and one that can be treated successfully with the administration of progesterone. The histologic diagnosis of luteal phase defect may also be confirmed with serum progesterone.