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Biomedical subjects

S Daya

Publications and source records attributed to S Daya.

At least 19 recordsLinked to original sources
PubMed2001

Paradoxical effects of copper and manganese on brain mitochondrial function.

Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.

2,6-Dichloroindophenol↗
PubMed2001

A sensitive and reliable method for the detection of lipid peroxidation in biological tissues.

A simple, accurate and cost effective method has been designed for the determination of lipid peroxidation in biological tissue samples. The method was a modification and improvement on existing methods available for lipid peroxidation determination. Solid-phase extraction was used to separate the thiobarbituric acid-malondialdehyde complex from thiobarbituric acid-reactive substances and HPLC was performed using a C18 (Waters Spherisorb, 5 microm, 250 x 4.6 mm i.d.) column to achieve isolation of the complex. The procedure was validated with respect to linearity of calibration (0.998), precision, sensitivity and limits of quantitation (1 nmol mL(-1)) and detection (0.5 nmol mL(-1)). Resorcinol was used as an external standard. The method was tested by inducing free radical generation with a known free radical generator, quinolinic acid, in rat brain homogenate. The results showed that the method presented allowed detection of lipid peroxidation products at concentrations in the nanomolar (nM) range compared with the micromolar (microM) range detected by other methods, thus rendering it suitable for use with biological samples. In addition, the modified method allowed for detection of the purified lipid peroxidation products, thus eliminating the possibility of simultaneous detection of impurities that absorb at the same wavelength.

Animals↗
PubMed2000

Acetaminophen inhibits liver trytophan-2,3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindole acetic acid.

The effect of the analgesic agent, acetaminophen was determined on rat forebrain serotonin levels as well as hepatic tryptophan-2,3-dioxygenase (TDO) activity and urinary 5-hydroxyindole acetic acid (5-HIAA). The results show that acetaminophen administration (100mg/kg) over three hours does not affect the holoenzyme of tryptophan-2,3-dioxygenase but significantly inhibits the apoenzyme. This inhibition is accompanied by a concomitant rise in forebrain serotonin levels. This phenomenon is also accompanied by a reduction in urinary 5-HIAA levels. These results suggest that acetaminophen use is accompanied by changes in brain serotonin levels due to inhibition of hepatic tryptophan-2,3-dioxygenase activity. This in turn could explain the possible abuse potential of acetaminophen and its effects on mood at high doses.

Acetaminophen↗
PubMed2000

Follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in assisted reproduction cycles.

OBJECTIVES: To conduct a systematic overview of available data comparing FSH and hMG in IVF treatment cycles. SEARCH STRATEGY: This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified in the Group's Specialised Register of Controlled Trials. See Review Group details for more information. DATA COLLECTION AND ANALYSIS: A systematic review and meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Common odds ratios (OR) were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN RESULTS MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle started, per cycle reaching oocyte retrieval, and per cycle reaching embryo transfer (ET). RESULTS: Eight trials met the inclusion criteria. The overall OR in favour of FSH for cycle start, oocyte retrieval, and ET were 1.70 (95% CI, 1.11-2.60), 1.68 (95% CI, 1.10-2.56), and 1.69 (95% CI, 1.10-2.59), respectively. REVIEWER'S CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Female↗
PubMed2000

Gonadotropin releasing hormone agonist protocols for pituitary desensitization in in vitro fertilization and gamete intrafallopian transfer cycles.

BACKGROUND: Gonadotropin releasing hormone agonists (GnRHa) are used in assisted reproduction cycles to reversibly block pituitary function and prevent a luteinizing hormone surge. In the short and ultrashort protocols of GnRHa administration, injection of gonadotropins is commenced a few days after the start of GnRHa. In the long protocols (with GnRHa started either in the midluteal phase or in the early follicular phase) gonadotropin administration is delayed until pituitary desensitization has been achieved, usually 2-3 weeks. OBJECTIVES: To conduct a systematic overview of available data comparing short or ultrashort and long GnRHa protocols for pituitary desensitization in in vitro fertilization (IVF) and gamete intra-fallopian transfer (GIFT) treatment cycles. SEARCH STRATEGY: Search strategies included on-line searching of the MEDLINE and EMBASE data bases and the Cochrane Menstrual Disorders and Subfertility Group's Specialised Register from 1982 to 1998, and hand searching of bibliographies of relevant publications and reviews, and abstracts of scientific meetings. SELECTION CRITERIA: Randomized trials of short or ultrashort versus long (follicular or luteal phase start) GnRHa protocols in IVF or GIFT treatment cycles. DATA COLLECTION AND ANALYSIS: Data were extracted into 2 x 2 tables. For the primary outcome, clinical pregnancy per cycle started, the overall common odds ratio (OR) and the risk difference with 95% confidence interval (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. The following subgroup comparisons were performed: ultrashort versus long protocols, short versus long protocols and, within each of these comparisons, subgroups of studies which used the long protocol with follicular phase start or the long protocol with luteal phase start. Secondary outcomes considered were clinical pregnancy per oocyte retrieval and per embryo transfer, spontaneous abortion, ongoing/delivered pregnancy per cycle started, number of ampoules of gonadotropin used, number of oocytes retrieved, and fertilization rate. MAIN RESULTS: Twenty-six trials met the inclusion criteria. The common OR for clinical pregnancy per cycle started was 1.32 (95% CI, 1.10 - 1.57) in favour of the long GnRHa protocol. The studies were subgrouped, depending on whether, in the long protocol, the GnRHa was commenced in the follicular phase (8 trials) or luteal phase (16 trials). The respective ORs were 1.54 (95% CI, 1.11 - 2. 13) and 1.21 (95% CI, 0.98 - 1.51). After excluding the four trials using the ultrashort protocol, the OR for long versus short protocols (22 trials) was 1.27 (95% CI, 1.04 - 1.56). A comparison of long versus ultrashort protocols (4 trials) produced an OR of 1. 47 (95% CI, 1.02 - 2.12). REVIEWER'S CONCLUSIONS: On the basis of clinical pregnancy rate per cycle started, this meta-analysis demonstrates the superiority of the long protocol over the short and ultrashort protocols for GnRHa use in IVF and GIFT cycles.

Female↗
PubMed2000

Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction cycles.

BACKGROUND: Until recently, the main source of exogenous follicle stimulating hormone (FSH) for therapeutic use in infertility had been the urine of postmenopausal women. New developments have resulted in the production of FSH in vitro by recombinant DNA technology. The extremely high purity and batch-to-batch consistency of recombinant FSH (rFSH) make it an attractive alternative to urinary FSH (uFSH). OBJECTIVES: To conduct a systematic review and meta-analysis of randomized trials comparing the effectiveness of rFSH with uFSH in ovarian stimulation protocols in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) treatment cycles. SEARCH STRATEGY: Search strategies included on-line searching of the MEDLINE and EMBASE databases from 1985 to 1999, hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings, peer consultation and contacting the pharmaceutical companies that manufacture the gonadotropins under consideration. SELECTION CRITERIA: Randomized trials comparing rFSH with uFSH for ovarian stimulation in IVF or ICSI treatment for infertility. DATA COLLECTION AND ANALYSIS: The main outcome measure was clinical pregnancy per cycle started. Also considered were clinical pregnancy per cycle reaching oocyte retrieval and per cycle reaching embryo transfer (ET), ongoing pregnancy per cycle started, spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, total dose of FSH, and number of oocytes retrieved. Common odds ratios (OR) and risk differences for rFSH relative to uFSH were calculated after testing for homogeneity of treatment effect across all trials. The fixed effects model was used, unless significant heterogeneity was present, in which case the random effects model was used. MAIN RESULTS: The overall odds ratio for clinical pregnancy per cycle started was 1.21 (95% confidence limits (CL) 1.04,1.42) for rFSH compared to uFSH. The risk difference was a 3.7% (0.8,6.7) absolute increase in clinical pregnancy rate with rFSH. The OR for ongoing pregnancy per cycle started was 1.29 (1.08,1.54). There was no significant difference between rFSH and uFSH in the rates of spontaneous abortion, multiple pregnancy or OHSS. The total dose of FSH was lower by 406 (185,627) IU with rFSH, but there was no significant difference in the number of follicles or serum estradiol on hCG day or in the number of oocytes retrieved. REVIEWER'S CONCLUSIONS: This review has demonstrated a statistically significant increase in clinical pregnancy rate with rFSH compared to uFSH, when used for ovarian stimulation in assisted reproduction. This benefit was observed only in standard IVF cycles and not in cycles in which ICSI was used.

Adult↗
PubMed2000

Cyanide-induced free radical production and lipid peroxidation in rat brain homogenate is reduced by aspirin.

The neuroprotective properties of aspirin were investigated using cyanide-induced neurotoxicity as model. Cyanide, a known neurotoxic agent significantly increased lipid peroxidation and superoxide anion levels in rat brain homogenate in a concentration-dependent manner (0.25-1.0 mM). When homogenate, containing 1.0 mM KCN was co-treated with aspirin (1.0 mM) there was a significant decrease in lipid peroxidation. Aspirin (0.5 mM and 1.0 mM) also significantly reduced KCN-induced superoxide anion generation. The results of the present report therefore indicate a neuroprotective role for aspirin.

Animals↗
PubMed2000

The alternating-sequence design (or multiple-period crossover) trial for evaluating treatment efficacy in infertility.

OBJECTIVE: To determine whether a constant-sequence or an alternating-sequence design is better for the evaluation of infertility treatment efficacy when multiple cycles of treatment are undertaken. DESIGN: A simulation exercise using analytical methods. SETTING: University medical center. PATIENT(S): A hypothetical, heterogeneous population of infertile patients participating in a randomized trial comparing an experimental treatment, with effectiveness of 2.0, to no treatment. INTERVENTION(S): Comparison of a constant-sequence design in which the subject receives the same intervention or the alternating-sequence design in which experimental and control treatments are crossed over after each successive cycle. MAIN OUTCOME MEASURE(S): Relative risks of pregnancy per cycle and overall after a maximum of five cycles of treatment. RESULT(S): With both designs, the pregnancy rates in experimental and control groups showed a consistent decrease with each successive cycle. The overall effectiveness in the constant-sequence design was underestimated at 1.83, whereas in the alternating-sequence design it was overestimated at 2.06. However, by restricting the analysis in the latter design only to the odd-numbered cycles, the relative risk was precisely correct at 2.00. CONCLUSION(S): When multiple cycles of treatment are undertaken to evaluate the efficacy of infertility therapy, the alternating-sequence design with restriction of the analysis to only the odd-numbered treatment cycles provides an unbiased estimation of the treatment effect.

Clinical Trials as Topic↗
PubMed2000

Effects of alendronate and hormone replacement therapy, alone or in combination, on bone mass in postmenopausal women with osteoporosis: a prospective, randomized study.

The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and in combination, was evaluated in 120 postmenopausal patients with osteoporosis with bone mineral density (BMD) measurements at least 2 SD below the mean value for young premenopausal subjects. They had no contra-indications to HRT or alendronate use and were randomized to three different treatment groups. Group I was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1 mg/day per os, group II received alendronate 10 mg/day per os and group III received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day was supplied to patients in all three groups. Spinal and femoral neck BMD and markers of bone mineral metabolism were measured on each patient before treatment and 6 and 12 months after treatment in 95 patients. At the end of the 12th month, significant increases in spinal and femoral neck BMD were found in all groups. Increases in spinal BMD were significantly higher in patients treated with alendronate and alendronate with HRT when compared with patients treated with HRT only. No significant difference was found in femoral neck BMD changes between the groups. Significant decreases in bone resorption and markers of bone formation were observed in all groups. Alendronate was found to be more effective than HRT and could have a very beneficial effect when added to the HRT regimen in patients with postmenopausal osteoporosis. Alendronate might also be used in postmenopausal patients with osteoporosis when HRT is contra-indicated or when there is reluctance to use hormonal treatment.

Alendronate↗
PubMed2000

Cost-effective, evidence-based infertility care.

Economic evaluation of health care interventions is becoming increasingly important as the demand for services increases. For unexplained infertility, in-vitro fertilization is not a cost-effective first-line treatment option compared with ovarian stimulation and intrauterine insemination. In clomiphene citrate-resistant polycystic ovarian syndrome, in-vitro fertilization may be cost-effective.

Cost-Benefit Analysis↗
PubMed1999

Melatonin reduces quinolinic acid-induced lipid peroxidation in rat brain homogenate.

The protective effects of melatonin against the neurotoxin, quinolinic acid, were investigated in rat brain homogenate using the thiobarbituric acid assay. Quinolinic acid increased lipid peroxidation in a dose dependent manner. When homogenate was cotreated with melatonin there was a significant decrease in lipid peroxidation. The results of the present report show that melatonin may play a protective role in the brain against the neurohormone quinolinic acid, which has been identified as a causative agent in Huntington's Disease.

Animals↗
PubMed1999

Alterations in cardiac flow parameters in patients with polycystic ovarian syndrome.

The aim of this study was to examine the echocardiographic profiles of patients with polycystic ovarian syndrome (PCOS). Serum concentrations of follicle stimulating hormone, luteinizing hormone, androstenedione, free testosterone, prolactin, DHEA-SO(4) and 17-OH-progesterone, lipid profile (high and low density lipoproteins, triglyceride and total cholesterol) and basal and total insulin after a glucose tolerance test were measured in 35 patients with PCOS and 35 healthy controls matched for body mass index. Doppler, two dimensional M mode echocardiography was performed for the following indices: isovolumetric relaxation time (IVRT), E wave duration time (EVT), A wave duration time (AVT), E wave deceleration time (DT), peak early diastolic flow velocity (PEV), peak late diastolic flow velocity (PAV), E wave velocity time integral (FVI-E), A wave velocity time integral (FVI-A), atrial filling fraction (AFF), ejection fraction (EF), pre-ejection time (PEP), ejection time (ET) and aortic flow velocity time integral (FVI). Androstenedione, free testosterone, low density lipoproteins and cholesterol concentrations were significantly higher in patients with PCOS. There was no difference in basal and total insulin concentrations. IVRT, AVT, FVI-A, AFF, and PEP were higher in patients with PCOS, while PEV, FVI-E, EF, ET, EVT and EVT/AVT were higher in the control group. There was a positive correlation between basal insulin values and IVRT, and between total insulin values and EF. These changes are consistent with a non-restrictive type of diastolic dysfunction and left ventricular stiffness. PCOS may lead to diastolic dysfunction via hyperinsulinaemia and male type dyslipidaemia.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction.

The recent availability of recombinant follicle stimulating hormone (rFSH), with its high level of purity and batch-to-batch consistency has made it an attractive alternative to urinary FSH (uFSH) for ovarian stimulation. Several trials have compared the two preparations, but none had sufficient power to detect a clinically meaningful difference in pregnancy rates. The purpose of this study was to determine the clinical pregnancy rates per started cycle by pooling data from randomized trials which compared the use of rFSH and uFSH in treatment cycles using in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A thorough search of the literature identified 12 trials which met the inclusion criteria. In four trials, both IVF and ICSI were performed, in seven trials only IVF was performed and in one trial only ICSI was performed. Data were extracted and pooled using the principles of meta-analysis. There was no significant heterogeneity of treatment effect across the trials. The common odds ratio and the risk difference (and their 95% confidence intervals), obtained by pooling the data using a fixed effects model, were 1.20 (1.02-1.42) and 3.7% (0.5-6.9%) respectively, in favour of rFSH. The pregnancy rate with the alpha preparation of rFSH was statistically significantly higher than with uFSH in IVF cycles. The overall conclusion from this meta-analysis is that the use of rFSH in assisted reproduction is preferred over uFSH.

Female↗
PubMed1998

Influence of the antidepressants desipramine and fluoxetine on tryptophan-2,3-dioxygenase in the presence of exogenous melatonin.

The effects of desipramine and fluoxetine were examined on rat hepatic tryptophan-2,3-dioxygenase activity in the presence or absence of exogenous melatonin. Male Wistar rats were treated intraperitoneally over 8 days. The antidepressants were also administered individually and their impact on the enzyme noted. Desipramine reduced basal hepatic tryptophan-2,3-dioxygenase activity in the liver while fluoxetine had no observable effect. However, fluoxetine also prevented the hemin induced elevation in total enzyme activity. Exogenous melatonin (0.25mg/kg/day) for 8 days counteracted the inhibitory effects of both desipramine and fluoxetine at concentrations of 2.5mg/kg/day. Total enzyme activity was restored when melatonin was administered in combination with either drug. The experimental findings indicate that there is chemical antagonism at the surface of the enzyme between melatonin and the antidepressants that abolishes the observed inhibitory effects of the administered compounds.

Animals↗
PubMed1998

Melatonin plays a protective role in quinolinic acid-induced neurotoxicity in the rat hippocampus.

The neuroprotective effect of melatonin against the quinolinic acid-induced degeneration of rat hippocampal neurons was investigated. Three groups of rats were given intrahippocampal injections of either; saline, quinolinic acid or i.p. injections of melatonin prior to and after being injected with quinolinic acid. On the fifth day after the intrahippocampal injections the brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor binding studies. The results show that melatonin protects hippocampal neurons from quinolinic acid-induced neurodegeneration and partially prevents the decrease in glutamate receptor numbers caused by quinolinic acid. Thus, melatonin has the potential to reduce hippocampal neuronal damage induced by neurotoxins such as quinolinic acid.

Animals↗
PubMed1998

Steroidogenesis in luteinized granulosa cell cultures varies with follicular priming regimen.

During follicular development, a co-ordinated gonadotrophin and endocrine environment is believed to be essential for normal function of the resulting corpus luteum. Whether differences in the gonadotrophins used to promote follicular development can have lasting effects on granulosa cells after they have undergone luteinization and culture, remains to be studied. We measured steroid production under basal and human chorionic gonadotrophin (HCG) stimulation in short and long term cultures of luteinizing granulosa cells obtained from normal ovulatory women undergoing assisted folliculogenesis with either human menopausal gonadotrophin (HMG) or follicle stimulating hormone (FSH). Basal progesterone and oestradiol production by luteinized granulosa cells obtained from follicles stimulated to develop with FSH was significantly greater than that from HMG derived follicles (P < 0.001). In short term cultures, treatment with 10 IU HCG caused a 10-fold increase in progesterone release by cells from FSH stimulated follicles, whereas cells of HMG origin produced only 5-fold more progesterone (P < 0.0001). In cultures that were maintained for 2 weeks, progesterone secretion was reduced, but a similar trend in HCG responsiveness was observed. These experiments demonstrate that the composition of the gonadotrophins used to promote follicular development in vivo leads to differences in granulosa cell steroidogenesis which are evident after luteinization and culture. They additionally support the notion that the environment of follicular development will be reflected in the resulting corpus luteum.

Cells, Cultured↗