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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

The effect of copper on (3H)-tryptophan metabolism in organ cultures of rat pineal glands.

Copper toxicity has been implicated in various neurodegenerative disorders such as Wilson's disease and Alzheimer's disease. Free copper in the brain is toxic and leads to neuronal and cellular damage, through free radical generation. Melatonin has been investigated as a possible copper ion chelator. Melatonin could prevent copper-induced neuronal and cellular damage through binding with copper and preventing copper-induced free radical generation. The effect of copper on pineal indolamine synthesis has not been studied extensively. In the present study, copper (2 mg/kg) and melatonin (12 mg/kg) were administered daily to Wistar rats for a 2-week and 6-week period. Pineal organ culture was utilized to monitor pineal indolamine synthesis. The pineals from the 2-week copper/melatonin-treated group showed a statistically significant decrease in 5-methoxytryptophol synthesis (p < 0.01), compared to the pineals from the copper-treated group. Conversly, in the 6-week experiment, 5-methoxytryptophol synthesis was increased in both the copper- and copper/melatonin-treated groups. There was a statistically significant decrease in the N-acetyl serotonin level in the pineals from the 6-week copper-treated animals, as compared to the control- and copper/melatonin-treated group (p < 0.01). These results imply that copper reduces N-acetyltransferase activity, which results in a decrease in N-acetyl serotonin synthesis. Melatonin when coadministered with copper appears to prevent the N-acetyltransferase inhibition by copper. Copper exerts contradictory effects on 5-methoxytryptophol synthesis. Further investigations need to be carried out to examine the effects of copper on the pineal enzymes.

Animals↗
PubMed2001

17Beta-estradiol attenuates quinolinic acid insult in the rat hippocampus.

A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol quinolinic acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or quinolinic acid. The results show that 17beta-estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.

Animals↗
PubMed2001

Interaction of serotonin and melatonin with sodium, potassium, calcium, lithium and aluminium.

In the present study, we investigated the ability of serotonin and melatonin to bind metals that occur naturally in the brain. An electrochemical technique called adsorptive cathodic stripping voltammetry (AdCSV) was employed to study the metal-serotonin or metal melatonin interactions. The results show that both serotonin and melatonin form stable complexes with lithium and potassium, with serotonin favouring lithium over potassium, and melatonin favouring potassium over lithium. Coordination between either serotonin or melatonin and calcium was not favoured. The stability of the complexes formed between serotonin and the metals decreased with the metals as follows: Li+ > K+ > Al3+ > Na+ > Ca2-. The trend for melatonin-metal complexes was K+ > Li+ > Na+ > Al3+ > Ca2+ The binding and stable complex formation between both ligands, serotonin and melatonin with lithium, potassium and sodium is of biological importance. The binding of serotonin to lithium could provide an explanation for the therapeutic effects of lithium in depression treatment, whereas the binding of aluminium by melatonin could provide insight into the role of this element in the aetiology of Alzheimer's disease.

Aluminum↗
PubMed2001

The effect of variations in pH and temperature on stability of melatonin in aqueous solution.

Melatonin (N-acetyl-5-methoxytryptamine) has a diverse range of functions, including the control of neuroendocrine events. A number of studies have shown that melatonin may be of potential benefit for the treatment of insomnia, as well as neurodegenerative disorders. At present, there are numerous dosage forms of melatonin, with the oral route of administration being most popular. Presently, there is little information on the stability of melatonin over a pH range. With the changes in pH in the gastro-intestinal tract, as well as in different experimental conditions, information on the stability of melatonin would be important. We used a high-performance liquid chromatography method to determine the stability of melatonin solutions over a pH range (1.2-12) at room temperature and at 37 degrees C over a period of 21 days. The results show that no melatonin degradation occurred in the first 2 days. From days 3 to 21, there was a gradual decline in melatonin at all pHs, with the decline not exceeding 30%. No decline in melatonin levels occurred in the first 2 days at 37 degrees C. From days 3 to 21, melatonin levels declined gradually, with the decline not exceeding 29%.

Administration, Oral↗
PubMed2001

Potential dangers in the customary methods of conducting meta-analyses. Lack of bias in the meta-analysis of recombinant versus urinary follicle stimulating hormone.

In a meta-analysis of randomized trials comparing recombinant and urinary FSH for ovarian stimulation in infertility treatment cycles, the clinical pregnancy rate per cycle started was significantly higher with recombinant FSH. Before the results of the different trials can be pooled, it is important to determine whether the results are homogeneous so that one can obtain an overall treatment estimate that is without bias. There are several methods to ascertain lack of homogeneity, including logistic regression analysis, sensitivity analysis comparing fixed-effect and random-effect models, testing based in the chi2 distribution, and graphical methods comparing event rates in experimental and treatment groups. These methods all confirmed that the treatment effect was homogeneous across all trials thereby providing assurance that the overall conclusion of the superior efficacy of recombinant FSH compared with urinary FSH is based on an unbiased analysis.

Bias↗
PubMed2001

Cost-effectiveness modelling of recombinant FSH versus urinary FSH in assisted reproduction techniques in the UK.

BACKGROUND: The purpose of this study was to undertake an economic evaluation to compare the cost-effectiveness of recombinant (r)FSH with urinary (u)FSH for attaining clinical pregnancy with assisted reproduction. METHODS: Mathematical modelling was utilized incorporating a Markovian decision framework and a Monte Carlo simulation. Statistical representations of recurrent events over time were incorporated into a decision analysis involving fresh and frozen cycles in any sequence (after the first fresh embryo transfer cycle) over three successive assisted reproduction attempts. The mean values of transition probabilities were derived from randomized controlled clinical trials and published reports. The distributions of these transition probabilities were agreed upon by a panel of experts. Cost data for procedures and drugs were derived and validated according to the perspectives of the National Health Service and private clinics in the UK. RESULTS: The study involved 5000 Monte-Carlo simulations of treatment on a Markov cohort of 100 000 patients. The total number of pregnancies attained was significantly higher in the rFSH (40 575) compared with the uFSH (37 358) group. The cost per successful pregnancy was significantly lower for rFSH (5906 pounds sterling) compared with uFSH (6060 pounds sterling) and overall, fewer cycles of treatment were required with rFSH to achieve an ongoing pregnancy. The incremental cost-effectiveness ratio is 4148 pounds sterling for each additional clinical pregnancy with rFSH. CONCLUSIONS: In addition to the increased effectiveness of rFSH in ART, this study demonstrated that it is more cost-effective and more efficient than uFSH in attaining an ongoing pregnancy.

Cost-Benefit Analysis↗
PubMed2001

The potential for eye bank limbal rings to generate cultured corneal epithelial allografts.

PURPOSE: Patients with severe limbal deficiencies are unable to maintain a stable corneal surface. If sheets of cultured allogeneic corneal epithelium could be prepared from eye banked corneal limbal rings, which are normally discarded after keratoplasty, the sheets may be beneficial for grafting onto patients with limbal stem cell deficiencies. METHOD: Biopsies of limbal tissue (2-3 mm2) removed from organ-cultured corneal limbal rings or from fresh whole globes were either trypsinized or set up as explants to assess their potential for corneal epithelial cell production. RESULTS: Several biopsies were taken from each of 21 organ-cultured limbal rings and 10 fresh cadaveric globes. Cultures were generated from every cadaveric eye (10/10), although not all biopsies from the same eye gave rise to cultures. Confluent sheets of cultured cells were also produced successfully from limbal rings that had been in organ culture for up to 25 days, but the success rate from limbal ring material was variable (14/21). An analysis of parameters associated with each limbal ring was carried out in an attempt to identify the reasons for the different efficiencies of epithelial production. No obvious single parameter correlation was detected, although there was a trend to poorer efficiency with increased donor age. CONCLUSIONS: Confluent sheets of cultured corneal epithelial cells, suitable for grafting, can be produced from limbal tissue taken from eye bank organ-cultured corneas, although it takes longer, on average, to reach confluence (17-21 days) than an equivalent sample from a fresh eye (9-12 days).

Adolescent↗
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

An investigation into the neuroprotective properties of ibuprofen.

There is increasing evidence suggesting a protective role for anti-inflammatory medications in neurological disorders such as Alzheimer's disease (AD). While there has not been any direct evidence for this, a number of clinical studies indicate that those patients who have had a history of nonsteroidal anti-inflammatory use, have a lower incidence of AD. Since there is currently no evidence on the mechanism by which these agents offer possible neuroprotection, we investigated the potential neuroprotective properties of the nonsteroidal anti-inflammatory drug, ibuprofen, by examining whether this agent could reduce lipid peroxidation and superoxide radical generation. Quinolinic acid and cyanide, known neurotoxins, were used to induce lipid peroxidation and superoxide anion formation respectively, in rat brain homogenate. The results show that ibuprofen significantly (p<0.05) reduced quinolinic acid-induced lipid peroxidation and cyanide-induced superoxide production. The results of the present report therefore suggest a possible mechanism for the neuroprotective effect of ibuprofen.

Animals↗
PubMed2000

17Beta-estradiol protects against quinolinic acid-induced lipid peroxidation in the rat brain.

The neurotoxin quinolinic acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17beta-estradiol on lipid peroxidation induced by quinolinic acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 microg 17beta-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 micromol quinolinic acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with quinolinic acid alone or in combination with 17beta-estradiol. Quinolinic acid increased lipid peroxidation in a dose dependent manner in vitro, while homogenate co-treated with 17beta-estradiol showed a significant reduction in lipid peroxidation. 17Beta-estradiol was also shown to be protective against quinolinic acid in vivo. These results could explain the neuroprotective effect of 17beta-estradiol.

Animals↗