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Biomedical subjects

A Suri

Publications and source records attributed to A Suri.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacokinetic-pharmacodynamic relationships for analgesics.

A major goal of current pain research is to develop scientifically-based guidelines to optimize selection of analgesic drug doses and control pain. Numerous clinical studies have shown that the drug dose required to effectively alleviate pain is often highly variable, both between patients and between pain episodes in individual patients. This high variability makes it difficult to predict appropriate dosing regimens that will adequately control pain in the individual patient. The result is a "trial and error" approach to analgesic therapy. Experimental tools that measure analgesic response and drug disposition after administration of analgesics can be used to better predict the therapeutic effects of analgesics in individual patients. The approach defines factors that contribute to variability in therapeutic response. Pharmacokinetic-pharmacodynamic (PK/PD) modeling involves analysis of drug disposition data and drug efficacy data. Modeling depends on sensitive and reliable methods to quantify both pain and plasma (or other body fluid) levels of analgesic agents. Two major approaches have been used to quantify pain. The first utilizes subjective reports from patients, while the second employs physiological correlates of pain, such as evoked potentials. Results from PK/PD analysis that successfully identify a relationship between drug dose, drug concentration, and effect can be used to predict the effects of drug dose on analgesic effect in individuals. The ultimate goal is to provide patients with better pain relief by understanding variables that affect the analgesic concentration/effect relationship. This review examines the available pharmacokinetic-pharmacodynamic (PK/PD) data for selected opioid and nonopioid analgesics. Even though most analgesics are used clinically in multiple doses, the majority of PK/PD studies conducted to date evaluate single dose effects. Further studies with multiple doses are required to evaluate the validity of PK/PD relationships defined from single dose studies.

Analgesics↗
PubMed1996

A 3 milliTesla 60 Hz magnetic field is neither mutagenic nor co-mutagenic in the presence of menadione and MNU in a transgenic rat cell line.

The mechanisms by which an electromagnetic field (EMF) influences biological material are poorly understood. One potentially important model suggests that a magnetic field can stabilize free radicals in such a way as to permit their dispersement rather than their return to the ground state (Okazaki et al., 1988; Scaiano, 1995). We have tested this hypothesis by examining mutagenesis in the E. coli lacI gene target carried in the Big Blue rat embryo fibroblast cell line, R2 lambda LIZ. Mutant frequencies were determined in cells exposed to a magnetic field, cells pretreated with the mutagens N-methylnitrosourea (MNU) or 2-methyl-1,4-naphthoquinone (menadione), prior to being held in a 60 Hz 3 milliTesla (mT) magnetic field and cells concurrently exposed to the mutagens and the magnetic field. Menadione was selected because its mutagenic mechanism involves the formation of free radicals, while MNU is an alkylating agent not thought to act through radical formation. According to the radical stabilization hypothesis the application of a magnetic field to menadione treated cells would accentuate the mutagenic effects. Our results failed to indicate that the magnetic field affects mutagenesis by the oxygen-radical mediated mutagen, menadione.

Alkylating Agents↗
PubMed1996

Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials.

Pain assessment in human volunteers is difficult, and it often requires a large number of subjects to show analgesic efficacy with statistical significance. Electrical tooth pulp stimulation elicits a painful sensation and produces an electroencephalographic (EEG) signal that can be recorded from the scalp when precisely controlled dental stimuli are delivered. These somatosensory evoked potentials (EP) consist of a series of peaks or waves each characterized by their polarity, latency, and amplitude. They are obtained by processing the EEG signals that occur after tooth pulp stimulation. There is good correlation between subjective pain reports and evoked potential amplitudes (N150-P250 component). Thus, EP may provide a useful model for the assessment of analgesic activity in human volunteers. We describe an improved method for producing and recording tooth pulp evoked potentials in six healthy subjects. Only 16 EEG epochs were necessary to get a reproducible EP response from the participants. The approach was applied to study the efficacy of codeine (60 mg administered orally); a decrease in the evoked potential amplitudes after codeine administration was observed. The data were consistent with results from visual analog pain ratings given by the subjects.

Adult↗
PubMed1996

Potentiation of the effects of raclopride on sucrose consumption by the 5-HT2 antagonist ritanserin.

We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0-0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0-0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0-0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were tested. The concentration-intake function in drug-free rats was an inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3 mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell short of significance (P < 0.06) and intake of 34% sucrose was unchanged. Ritanserin did not affect sucrose intake when given on its own, but synergized with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake. These data indicate that 5-HT2 antagonism potentiated the behavioural effects of raclopride and we speculate that this interaction might contribute to the efficacy of atypical neuroleptic drugs.

Animals↗
PubMed1996

Identification of human sperm antigen recognized by serum of an immunoinfertile woman: a candidate for immunocontraception.

PROBLEM: It has been well documented that antisperm antibodies can be causative factors of infertility. In this study we have identified an antigen on human sperm surface using serum of an immunoinfertile woman; it is thus a candidate for immunocontraception. METHOD: Thirty-three women of reproductive age who were infertile were screened for presence of antisperm antibodies by indirect immunofluorescence and agglutination assay. The serum of one such woman, SU-4, reacted with her husband's as well as normal donor sperm and recognized a band of apparent molecular weight of 71-kDa on Western blot. Anti-71-kDa antiserum was raised in rabbit by eluting 71-kDa protein and was characterized by agglutination test, immunofluorescence assay, transmission electron microscopy, flow cytometry, and sperm-egg interaction in mouse system. RESULTS: Interestingly, sera raised in rabbit against 71-kDa antigen, was identified by immunoinfertile serum of SU-4, revealed similar results of localization of human acrosome. Anti-71-kDa antibodies showed cross-reactivity with other species of sperm, demonstrated inhibition of sperm attachment to oocytes in an in vitro mouse system, and revealed surface binding of human live sperm by flow cytometry. Transmission electron microscopy documented the presence of 71-kDa antigen in the acrosomal compartment. CONCLUSION: This study has put in evidence an antigen of apparent molecular weight of 71-kDa in all donor sperm tested in this study. The presence of this antigen on the sperm of several species will enable us to determine the efficacy of this antigen in controlling fertility in vivo in both rodents and primates. This antigen may be a candidate for immunocontraception.

Adult↗
PubMed1996

Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms.

BACKGROUND: This study was designed to evaluate the anxiolytic efficacy of buspirone in patients with a diagnosis of generalized anxiety disorder (GAD) with coexisting mild depressive symptoms. METHOD: Patients who participated in this multicenter study scored >/= 18 on the Hamilton Rating Scale for Anxiety (HAM-A) and between 12 and 17 on the Hamilton Rating Scale for Depression (HAM-D). Following a 7- to 10-day placebo lead-in phase, patients who continued to qualify were randomly assigned to receive either buspirone titrated from 15 to 45 mg/day (N = 80) or placebo (N = 82) for the next 6 weeks. 121 patients completed 6 weeks of treatment. The primary efficacy measure was the HAM-A, taken weekly during the study. RESULTS: Buspirone-treated patients averaged a 12.4-point reduction from their baseline total HAM-A score of 24.9, while their counterparts on placebo averaged a 9.5-point reduction from their mean baseline total HAM-A score of 25.6. This 2.9-point difference in HAM-A reductions between treatment groups was significantly different (p < .03). Buspirone patients decreased their HAM-D scores by an average 5.7 points from their mean baseline total HAM-D score of 15.8, while placebo patients decreased their HAM-D scores by an average 3.5 points from their mean baseline score of 16.3 (p < .05). Overall, the incidence of adverse events was similar for both treatment groups, but buspirone-treated patients reported significantly more nausea, dizziness, somnolence, and sweating than placebo patients. CONCLUSION: Buspirone is superior to placebo in improving anxiety and depressive symptoms in GAD patients who have coexisting depressive symptoms.

Adult↗
PubMed1995

Efficacy trial of the 5-HT2 antagonist MDL 11,939 in patients with generalized anxiety disorder.

The purpose of this study was to assess the anxiolytic effect of MDL 11,939, a selective 5-HT2 receptor antagonist, in patients with generalized anxiety disorder. After a 1-week placebo lead-in period, 72 healthy male outpatients meeting DSM-III-R criteria for generalized anxiety disorder were randomized to MDL 11,939, 32 mg thrice daily (N = 37), or placebo (N = 35) for 6 weeks. At the end of treatment, MDL 11,939 showed a 7.2-point (30%) decrease in Hamilton Rating Scale for Anxiety scores compared with a 5.7-point (23%) decrease with placebo, but the difference was not significant (p > 0.05). The incidence of adverse events between treatments was similar. MDL 11,939 was well tolerated but did not demonstrate significant anxiolytic effects in this pilot study.

Adult↗
PubMed1991

Characterisation of 24-kD proteins from rat testes using polyclonal sera reactive to human sperm antigens.

A group of antigens of 24-kD Mr from rat testes were characterised biochemically. These antigens were part of a larger molecule of approximately 200 kD. On treatment with disulfide bond reducing agent, the 200-kD molecule was reduced to subunits. Immunoreactivity was confined to a doublet of approximately 24 kD and a single band of approximately 50 kD Mr after the reduction. Glycoprotein in nature, this antigen shared immunoreactive epitopes with a 40-kD antigen on human spermatozoa. Antiserum raised in rabbits against the 24-kD antigen from rat testes reacted with antigens on the acrosome of human spermatozoa. Agglutination of sperm could be induced by the antiserum. The carbohydrate residue could be removed by mannosidase digestion. Chemical deglycosylation studies showed a slight decrease in molecular weight. Immunoreactivity was however not completely lost after chemical deglycosylation. Isoelectric focusing of the antigen identified nine isoelectric species. Two relatively minor species showed immunoreactivity. Acrosome-reacted spermatozoa showed loss of antigens from acrosome.

Acrosome↗
PubMed1990

Induction of infertility in female rats after active immunization with 24 kD antigens from rat testes.

A unique polyvalent antiserum against whole washed human sperm was used previously to identify groups of antigens on spermatozoa. The antiserum, designated as Antiserum I, recognized a 40 kD antigen in human sperm extracts. Antiserum I caused agglutination of human sperm and prevented interaction of mouse sperm and oocytes. This serum also recognized a band of 24 kD in rat testicular cytosol. In the present study this group of 24 kD proteins was used as an antigen preparation to actively immunize female rats. Immunization was carried out with two different adjuvants: nor-muramyl dipeptide and SPLPS (a thyalated derivative of lipopolysaccharide). Both groups of animals showed significant antibody titres as detected by indirect immunofluorescence and by sperm agglutination tests. In both groups over 80% of the animals remained infertile, compared to 13% of the controls. It is concluded that a group of antigens in rat testes recognized by Antiserum I offer promise as candidates for a contraceptive vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Characterization of a monoclonal antibody against a 24KD antigen from rat testis important for fertility regulation.

Monoclonal antibodies were raised against a 24KD antigen from rat testicular cytosol which was previously shown to produce antibody titres in rats with inhibitory effect on fertility. Of the 20 hybridoma clones selected for study, one clone HS-D5 was finally chosen for characterisation as it proved to be functionally promising. The clone was secreting IgM type of antibody. It produced strong agglutination of human sperm and prevented binding of hamster sperm to hamster oocyte. In localization studies it identified the acrosome of sperm of multiple species. Western blots with rat testicular cytosol and human sperm extracts showed a strong band at around 24KD with HS-D5. On Western blots from two dimensional gels, HS-D5 identified multiple spots at the region of 24KD. The mechanism of action of the antibody seemed to be at the level of interaction of the oocyte and spermatozoa.

Animals↗
PubMed1989

Activities of some serum enzymes in halothane reacted and non-reacted pigs.

Eight- and nine-week-old Hungarian Landrace pigs were tested with halothane as described by Laky et al. (1985). Immediately after the test blood samples were taken for determination of the activity of serum creatine kinase (CK), creatine kinase MB (CK-MB) isoenzyme, aldolase (ALD), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH). Elevated creatine kinase, creatine kinase MB isoenzyme and aldolase activities indicating enhanced susceptibility to stressors were found in 92% of the halothane reacted and 16% of the halothane non-reacted animals. In these individuals the activities of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase were also high. Data of the literature show a close relationship between enhanced susceptibility to stressors and halothane reaction in pigs. It was suggested, therefore, that determination of the activity of appropriate serum enzymes might be used for detecting this enhanced susceptibility.

Animals↗
PubMed1989

Vaccine for control of fertility.

Birth control vaccines constitute a new category of vaccines. Immunization with the objective of selectively blocking a physiological process differs in many respects from immunizing against pathogens. Conceptually, these widen the orbit of therapeutic intervention by immunological methods. Success recorded in making vaccines regulating fertility offers models to regulate any other physiological process in the body. At a practical level, the task of making such vaccines is beset with inherent difficulties and with new challenges. This article, dedicated to Avrion Mitchison, aims to discuss these problems and to record successes wherever achieved.

Family Planning Services↗
PubMed1989

Experimental paratuberculosis (Johne's disease)--studies on biochemical parameters in cattle.

Ten male Holstein-Friesian calves naturally infected by Mycobacterium paratuberculosis were experimentally re-infected orally at an average of 17 days. Monthly measurements were conduced of the following activities, in the period between post infection days 160 and 400: total protein (TPR), albumin (ALB), cholesterol (CHOL), triglycerides (TRIG), Zn and Cu concentrations as well as sorbitol dehydrogenase, lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), gamma-glutamyltransferase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), alkaline phosphatase and fructose-1,6-diphosphate aldolase (ALD). TPR, ALB, TRIG, and CHOL were reduced by day 400, in conjunction with disorders of digestion and absorption. Increased activities of CK, ALD, LDH, alpha-HBDH, AST and ALT primarily indicated damage to skeletal muscle and/or liver. Serum CK and ALD activities as well as TRIG and TPR concentrations may serve as aids to specific diagnosis of paratuberculosis, particularly in the advanced stage of the disease.

Animals↗
PubMed1988

Identification of sperm antigens that regulate fertility.

Polyclonal antisera were generated in rabbits against human sperm extracts. Out of many such antisera, one was selected (antiserum I) because it recognized relatively few antigens on Western blots. Antiserum I identified immunostainable material on the acrosome of human, monkey, rabbit, hamster, rat and mouse sperm. A detailed histochemical study using rat testes showed that the antigen was detectable on early spermatids and sperm, but not on less mature germ cells. Immunohistochemistry at the electron microscope level localized the antigen on the plasma membrane of rat sperm. In Western blots using human sperm extracts, the antibody recognized a major band with an apparent molecular weight (MW) of 40,000 and minor bands at 43,000 and 72,000. With extracts of monkey sperm and rat testicular cytosol, antiserum I recognized antigens of 69,000 and 23-24,000, respectively. Functionally, antiserum I produced strong agglutination of human sperm. It also prevented attachment of mouse sperm to mouse oocytes in vitro and reduced fertility when administered to female mice. These results suggest that antiserum I can be used as a possible reagent for selecting sperm antigens as components of a contraceptive vaccine.

Animals↗
PubMed1987

Renal ultrastructural markers in AIDS-associated nephropathy.

Renal tissues from two groups of patients with acquired immune deficiency syndrome (AIDS) were examined: Group A had severe proteinuria and varying degrees of renal insufficiency, designated AIDS-associated nephropathy (AAN), and Group B had no renal involvement. Control Group C consisted of patients with heroin-associated nephropathy (HAN) with proteinuria comparable to patients in Group A but without AIDS or its related complex (ARC). The most frequent finding, common to both AAN and HAN, was focal glomerular sclerosis. In contrast to HAN, AAN tissue showed mesangial hypocellularity, sparse interstitial infiltrates, severe tubular degenerative changes, tubular microcystic ectasia, Bowman's space dilatation, and presence of multiple complex inclusions both in the nuclei and cytoplasm in a variety of cells. Abundant tubuloreticular inclusions were found in the endothelial and occasionally in the interstitial cell cytoplasm. Nuclear bodies (NBs) were seen in greater frequency, complexity, size, and heterogeneity, and of budding configuration in Group A as compared with Groups B and C; NBs in Group C were mostly of simple types (I and II). In addition, a peculiar granulofibrillary transformation in many tubular and interstitial cell nuclei was observed in Group A. This transformation was rarely present in Group B and was never seen in Group C. Because complex NBs (Types III to V) and various intracytoplasmic and intranuclear inclusions present in Group A are often associated with viral invasion, their presence in kidneys of AIDS patients with proteinuria suggests a viral etiology for AAN.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Acinetobacter infection in neurosurgical intensive care patients.

BACKGROUND: This study was performed to analyse the incidence of Acinetobacter infections in neurosurgical patients in the postoperative period. METHODS: Two thousand three hundred and twenty postoperative cranial neurosurgical intensive care unit (ICU) patients were studied from March 1995 to August 1996; 419 patients had a variety of infections and 42 patients had multiple infections. Acinetobacter was isolated in 103 patients (24.6% of total patients infected and 4.4% of total patients analysed). Statistical analyses were performed to identify the risk factors, antibiotic sensitivity and outcome of therapy of Acinetobacter infection. RESULTS: Acinetobacter infection was not significantly related to the length of hospital stay prior to surgery but was related significantly to the length of stay in the ICU after surgery. Acinetobacter was isolated from sputum/tracheal secretions in 47/103 (45.6%), followed by cerebrospinal fluid [24/103 (23.3%)], urine [15/103 (14.56%)] and blood [15/103 (11.65%)]. Acinetobacter infection was present in 54 (3.21%) of 1680 patients who had undergone routine/elective surgery and in 49 (7.66%) of 640 patients following emergency surgery. Elective/supportive ventilation for > 5 days, external ventricular cerebrospinal fluid drainage for > 5 days, intracranial pressure monitoring and prolonged indwelling Foley's urinary catheter during the perioperative period were independent risk factors (p < 0.005). Acinetobacter isolated from sputum/tracheal secretions were mostly sensitive to amikacin, cefotaxime and ceftriaxone; while those grown from the cerebrospinal fluid were more often sensitive to ciprofloxacin, amikacin and netilmycin. Twenty-four patients succumbed to Acinetobacter infection; in 11 of these patients the organism was resistant to all antibiotics. CONCLUSION: Acinetobacter is an important nosocomial infection in neurosurgical intensive care patients.

Acinetobacter Infections↗