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Biomedical subjects

J Shah

Publications and source records attributed to J Shah.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients.

1. Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is being developed for the prevention of rejection following solid organ transplantation. This crossover study investigated the effect of food and antacid (Maalox TC) on the plasma pharmacokinetics of MPA and its inactive glucuronide metabolite MPAG after giving single 2 g MMF doses orally to rheumatoid arthritis patients. 2. With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA tmax was slightly delayed and Cmax was lowered about 25%, consistent with delay in gastric emptying in the fed state. MPAG Cmax and AUC were higher in the fed relative to the fasting state, suggesting more complex processes involving changes in glucuronidation may also be occurring with food. 3. With antacid, AUC of MPA was lowered about 15% compared with fasting and Cmax was decreased 37%. Plasma MPAG parameters were similarly reduced. These parallel changes in MPA and MPAG are consistent with reduced absorption. 4. The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest.

Administration, Oral↗
PubMed1996

Identification of a salicylic acid-responsive element in the promoter of the tobacco pathogenesis-related beta-1,3-glucanase gene, PR-2d.

The tobacco pathogenesis-related PR-2d gene encodes an acidic beta-1,3-glucanase. Expression of the PR-2d: uidA(GUS) chimeric gene is induced in leaves undergoing the hypersensitive resistance response to tobacco mosaic virus and after treatment with salicylic acid (SA), a chemical believed to play an important role(s) in disease resistance. We have constructed transgenic tobacco plants which carry various segments of the PR-2d promoter fused to a heterologous core 35S promoter driving the uidA(GUS) reporter gene. Their analysis indicates that sequences from -364 to -288 upstream of the PR-2d transcription start site confer a high level of activation by SA (20-fold). Mutations within this sequence, located between -339 and -333, depressed SA activation. This region is also required for the SA-inducibility of a truncated PR-2d:GUS chimeric gene. Contained within this region is a 25 bp element located between -348 and -324 which was specifically recognized by nuclear factors from tobacco leaves. No conclusive differences were observed in the ability of proteins in nuclear extracts from water-treated versus SA-treated plants to bind to this cis element in vitro.

Binding Sites↗
PubMed1995

Comparison of characteristics of Q beta replicase-amplified assay with competitive PCR assay for Chlamydia trachomatis.

In order to study infections due to Chlamydia trachomatis, we have compared semiquantitative PCR and Q beta replicase-amplified assays for detection of this organism. The PCR assay was directed against the C. trachomatis 16S rRNA gene. Quantitation was accomplished by adding known amounts of a plasmid containing a truncated segment of the 16S rRNA gene target to chlamydia-containing samples and then amplifying with a common primer set. The Q beta replicase assay consisted of reversible target capture of C. trachomatis 16S rRNA, which was followed by amplification of an RNA detector probe in the presence of the enzyme Q beta replicase. In a clinical matrix, the lower limit of detection of both the PCR and Q beta replicase assays was five elementary bodies. The Q beta replicase and PCR assays were quantitative over 10,000- and 1,000-fold ranges of organisms, respectively. Analysis of the effects of endocervical matrix on amplification was accomplished by examining 94 endocervical specimens by each technique. Both assays detected five of six culture-confirmed specimens as well as three culture-negative specimens. PCR inhibitors were detected in 13 specimens. The Q beta replicase assay, in contrast, showed no evidence of sample inhibition. The Q beta replicase and PCR assays should allow quantitative investigation of infections due to C. trachomatis. In addition, because it targets highly labile RNA, the Q beta replicase assay may facilitate investigations into the role of active persisting infection in culture-negative inflammatory conditions.

Base Sequence↗
PubMed1995

Comparison of amplified Q beta replicase and PCR assays for detection of Mycobacterium tuberculosis.

Because of the long time required to isolate Mycobacterium tuberculosis in culture, there is an acute need for simple rapid methods for direct detection of M. tuberculosis from human sputum specimens. We have developed and characterized quantitative manual Q beta replicase and PCR assays for M. tuberculosis. The Q beta replicase assay was based on reversible target capture of M. tuberculosis 23S rRNA followed by amplification of a replicatable detector probe with Q beta replicase. For PCR assays, primers generating a 370-bp amplification product from the IS6110 insertion element were used in combination with a control plasmid containing an internal deletion in the IS6110 amplicon. Serial dilutions of M. tuberculosis were spiked into sputum and subjected to digestion and decontamination with N-acetyl-L-cysteine and NaOH. Assay conditions were optimized for hybridization and sample processing chemistries in order to maximize sample utilization. Following assay optimization, the sensitivities of the Q beta replicase and PCR assays of spiked sputum samples were 0.5 and 5.0 CFU per assay reaction, respectively. The effects of sputum matrix on each assay were examined by testing 20 patient sputum samples which had been cultured for M. tuberculosis. The culture-positive samples included smear-positive and smear-negative samples. The results of the Q beta replicase assay were not inhibited by sputum and were in 100% agreement with those of culture, including detection of 10 culture-positive specimens. However, using an internal control plasmid coamplified with each PCR as an indicator, we detected PCR inhibition in 9 of 20 samples tested. Decreasing the amount of sample assayed in the PCR 24-fold alleviated the inhibitory effects in all but two specimens, one of which was culture positive. The decreased sample utilization also resulted in a false-negative result with a third specimen which was culture positive for M. tuberculosis. Quantitative smear results and QB replicase assay estimates of the number of organisms present in these specimens were in close agreement. The QB replicase assay performed well in comparison with both culture and PCR and should offer a rapid means for detecting and controlling infection due to M. tuberculosis.

Bacteriological Techniques↗
PubMed1995

Age-dependent alterations in Na+, K(+)-ATPase activity in the central nervous system of spontaneously hypertensive rats: relationship to the development of high blood pressure.

We have previously demonstrated that cerebroventricular administrations (i.c.v) of potassium chloride solutions (KCl; 0.375-1.25 mumoles/5 microliters) elicit ouabain-sensitive, concentration-dependent decreases in the blood pressure and heart rates of anesthetized, normotensive Sprague-Dawley (SD) rats. These studies have suggested an inverse relationship between Na(+)-pump activity in the central nervous system (CNS) and central sympathetic outflow. Such a view is further supported by the present studies showing that i.c.v. injections of KCl failed to produce any alterations in the blood pressures of rats pretreated with an autonomic ganglionic blocker, chlorisondamine. In the present studies, depressor responses to i.c.v. potassium chloride were considered as functional indices for evaluation of neuronal Na(+)-pump activity in 8 and 12 week old (8 wk and 12 wk) SHR, WKY and Sprague-Dawley (SD) rats. Basal arterial blood pressures of 8 wk-old SD and SHR, and the responsiveness of these two groups to i.c.v. potassium chloride solutions are similar and they both are significantly greater than that of age matched WKY. However, in the 12 wk-old groups, arterial pressure of SHR was significantly greater than that of WKY as well as SD, whereas the depressor responses to KCl in SHR were significantly greater than that of only WKY. Pretreatment of the rats with i.c.v. ouabain abolished the differences in the hypotensive responses to i.c.v. potassium chloride that existed between various groups but not the differences in the basal blood pressures. Evaluation of these data suggest that a) the centrally mediated hypotensive responses to K+ in various groups could depend upon Na+, K(+)-pump activity in C.N.S. and/or on basal central sympathetic discharge; b) central sympathetic activity is greater in SHR only when compared to WKY but not to SD; c) since the central Na(+)-pump activity and sympathetic tone appears to be similar in SHR and SD, mechanisms other than the increases in sympathetic activity must play a prominent role in the development of spontaneous hypertension; d) attenuation of neuronal Na(+)-pump activity cannot account for greater sympathetic tone in SHR and SD-rats when compared to WKY.

Aging↗
PubMed1995

The effect of patient controlled analgesia and continuous epidural infusion on length of hospital stay after total knee or total hip replacement.

The purpose of this study was to determine the correlation between patient controlled analgesia and continuous epidural analgesia after total knee or total hip replacement on the length of hospital stay. Stress responses to postoperative pain, including decreased mobility, compromised respiratory function, increased catecholamine release, and hypercoagulation, may adversely affect patient recovery, thus lengthening hospital stay. A retrospective chart review of 127 adult, American Society of Anesthesiology (ASA) I, II, or III, patients who had undergone total knee arthroplasty (TKA) or total hip replacement (THR) was obtained. One patient group received epidural anesthesia and postoperative analgesia (EAA) through continuous catheter infusion of bupivacaine or preservative free morphine. The second group underwent general anesthesia and postoperative patient controlled anesthesia (G-PCA) of meperidine hydrochloride or morphine. Length of stay (LOS) was defined as the time period beginning with admission to the post-anesthesia care unit (PACU) until 10 AM the day of discharge. The mean LOS, in hours, for EAA-morphine was 121; compared with EAA-bupivacaine, 142; G-PCA-meperidine, 134; and G-PCA-morphine, 142. These findings were not statistically significant at P = 0.054. LOS did not correlate with age, weight, height, type or surgery, or the ASA classification. Further research into the effectiveness of continuous infusion of epidural bupivacaine and epidural morphine and their impact on LOS may be warranted.

Analgesia, Epidural↗
PubMed1995

Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide: effect of hydration.

Differential scanning calorimetry (DSC) and X-ray diffraction techniques have been used to investigate the structure and thermotropic properties of synthetic, non-hydroxy fatty acid (16:0) ceramide (NFA(C16)CER) as a function of hydration. Anhydrous NFA(C16)CER shows a single, broad endothermic transition at 95.4 degrees C (delta H = 10.4 kcal/mol). On hydration, a broad exothermic transition appears at approximately 50-70 degrees C while the main endothermic transition decreases to 90.0 degrees C (delta H = 13.8 kcal/mol). The enthalpy of the exothermic transition increases with hydration to a maximum value, delta H = 4.8 kcal/mol. This polymorphic phase behavior depends on the low temperature incubation time and prior cooling rate. X-ray diffraction of fully hydrated NFA(C16)CER at 26 degrees C, shows a well-ordered lamellar phase with a bilayer periodicity d = 46.9 A. At 68 degrees C, above the first exothermic transition, X-ray diffraction shows again a lamellar phase with reduced bilayer periodicity d = 41.8 A and an increased number of both lamellar and wide-angle reflections indicative of enhanced layer and chain packing order, respectively. At 90.0 degrees C, above the main transition, the diffraction pattern shows a broad, intense reflection at 29.9 A and a diffuse reflection at 4.6 A, indicative of a melted chain phase. On cooling, NFA(C16)CER exhibits polymorphic phase behavior involving the conversion of the melted chain phase to a metastable bilayer phase. On heating, this metastable phase undergoes an exothermic transition to a stable bilayer phase; on further heating, NFA(C16)CER converts endothermically to the melted-chain phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗
PubMed1995

Physical properties of ceramides: effect of fatty acid hydroxylation.

The structural and thermotropic properties of alpha-hydroxy fatty acid (HFA) and non-hydroxy fatty acid (NFA) ceramides (CER) have been studied using differential scanning calorimetry (DSC) and X-ray diffraction techniques. The DSC of anhydrous HFA-CER shows a single, sharp reversible transition at 95.6 degrees C (delta H = 15.3 kcal/mol). At intermediate hydrations HFA-CER exhibited more complex behavior but at maximum hydration only a single reversible transition is observed at 80.0 degrees C (delta H = 8.5 kcal/mol). X-ray diffraction of hydrated (74% water) HFA-CER at 20 degrees C shows a lamellar structure with a bilayer periodicity d = 60.7 Angstrum; a single wide angle reflection at 4.2 Angstrum is characteristic of hexagonal chain packing. Above the main transition temperature at 91 degrees C, a hexagonal (HII) phase is observed. In contrast, DSC of anhydrous NFA-CER demonstrates two thermal transitions at 81.3 degrees C (delta H = 6.8 kcal/mol) and 85.9 degrees C (delta H = 3.5 kcal/mol). With increasing hydration, both transitions shift towards lower temperatures; at maximum hydration, on heating, the endothermic transitions occur at 72.7 degrees C (delta H = 9.8 kcal/mol) and 81.1 degrees C (delta H = 4.0 kcal/mol). On cooling, there is hysteresis of both transitions. X-ray diffraction of NFA-CER (80% water) at 20 degrees C shows a well-ordered lamellar structure with a bilayer periodicity d = 58.6 Angstrum and three wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum. At 77 degrees C (between the two transitions), again a lamellar structure exists with reduced bilayer periodicity d = 53.1 Angstrum and four wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum are observed. Above the second transition, only a single low angle reflection at 30.0 Angstrum is observed; a diffuse reflection at 4.6 Angstrum is indicative of a melted chain phase. Thus, HFA-CER exhibits a simple phase behavior involving the reversible conversion of a gel phase to a hexagonal phase (L beta-->HII). However, NFA-CER shows a more complex polymorphic phase behavior involving two gel phases.

Calorimetry, Differential Scanning↗
PubMed1995

Evaluation of immunogenicity and tolerance of single dose haemophilus influenzae type B (PRP-T) vaccine.

OBJECTIVE: Evaluation of immunogenicity and acceptability of PRP-T vaccine among the Indian children. DESIGN: Multicentric, open, parallel group, comparative study of Haemophilus influenzae type B vaccine, given as single (Group I) or associated (Group II) with DPT vaccine. SETTING: Five different vaccination clinics. SUBJECTS: 125 children between the age group of 18-24 months. PARAMETERS: Measurement of (i) pre and post vaccination antibody titres of Haemophilus influenze type B specific antibody; (ii) Adverse events; and (iii) Tolerance as graded by the physician. RESULTS: Prevaccination antibody levels were > 0.15 mcg/ml in 56.3% in Group I and 35.7% in Group II. Post-seroconversion was seen in 97% in Group II receiving single and all in Group II (P > 0.05). The vaccine was well tolerated. CONCLUSIONS: The probability of subclinical infection or cross immunity is high in India. ACTHIB vaccine has a good immunogenicity and tolerance and association with DPT does not modify the immunogenicity of ACTHIB vaccine.

Antigens, Bacterial↗