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Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 289 records · Page 16Linked to original sources

Human zona pellucida glycoproteins: characterization using antibodies against recombinant non-human primate ZP1, ZP2 and ZP3.

Characterization and classification of human zona pellucida glycoproteins is essential to understand the functions of these components during fertilization. To achieve this, antibodies were raised in rabbits against recombinant non-human primate [Bonnet Monkey (Macaca radiata)] zona pellucida proteins, bmZP1, bmZP2 and bmZP3 expressed in Escherichia coli. Antibodies against the three recombinant zona proteins reacted with human zonae as revealed by indirect immunofluorescence. Such antibodies were used as specific probes to further characterize human zona pellucida glycoproteins in Western blot of heat solubilized human zonae pellucidae (hSIZP) resolved by one dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Under non-reduced conditions human (h) hZP1, hZP2 and hZP3 resolved as 60, 100 and 53 kDa bands respectively. Under reduced conditions, dominant reactivity of hZP1, hZP2 and hZP3 was localized to 63, 65 and 58 kDa and faint reactivity to 53, 96 and 138 kDa bands respectively. In two-dimensional SDS-PAGE, hZP1 was shown to comprise two chains at 63-58 and 55-45 kDa, each consisting of multiple isomers. hZP2 was less acidic when compared with hZP1 and hZP3 and comprised a major component of 65 kDa and a minor component of approximately 96 kDa. The 65 kDa component displayed a higher degree of charged isomers in comparison with the 96 kDa component. hZP3 comprised a broad band in the range 68-58 kDa. These studies show conclusively that the hZP1 heavy train overlaps with hZP3 and that in previous studies, hZP2 was likely to have been misinterpreted as being hZP1. Our studies failed to distinguish two distinct species of hZP3, unlike previous reports. These studies will further help in our understanding of the nature of human zona pellucida glycoproteins.

Animals↗

Gross appearance of the turkey blastoderm at oviposition.

The blastoderm (fertilized ovum) and unfertilized germinal disc (UGD) of fresh laid eggs and eggs stored prior to incubation exhibit subtle but definable morphological variations. Such variations may lead to difficulty when attempting to determine true flock fertility based on the appearance of the blastoderm/UGD. The objectives of this study were to define and categorize such morphological variations and to determine whether sperm influence the frequency distribution of the different categories. Eleven categories of blastoderms were defined based on the relative density and appearance of the area alba, area pellucida, area opaca, and the periblast. The majority of the blastoderms were included in the first four categories. Unfertilized germinal discs were divided into six categories and were best differentiated from the blastoderms by the presence of vacuoles around its central dense area. They were also discernible from blastoderms based on their overall denser appearance. Differences in the frequency distribution of some of the UGD categories between virgin and inseminated hens may be due to the effect that supernumary sperm may have on the organization of the UGD (no fertilization but supernumary sperm present) or blastoderm (fertilized but failed to develop). It is recommended that before starting true fertility determinations during fresh egg breakouts, one should study the appearance of the UGD from virgin hens and then the blastoderm from inseminated hens. One then will learn to appreciate the subtle differences in shape and density of the blastoderm/UGD structural components.

Animals↗

Remifentanil pharmacokinetics in obese versus lean patients.

BACKGROUND: Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics. METHODS: Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed. RESULTS: The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations. CONCLUSIONS: The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.

Adolescent↗

Further studies of anti-endomysium and anti-gliadin antibodies in patients with suspected celiac disease.

BACKGROUND: The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health-care costs. The sensitivity and specificity of anti-gliadin antibodies (AGA-immunoglobulin [Ig] G, AGA-IgA) have been variable; anti-endomysium IgA (EmA-IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti-endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA-IgA in diagnosing celiac disease. METHODS: One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA-IgA was measured in all patients, and AGA-IgG and AGA-IgA were measured in 104 patients. Forty-six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients. RESULTS: Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2-9.5 years); one also had cystic fibrosis and another had insulin-dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA-IgA (100% sensitivity). None of the remaining patients had increased EmA-IgA (100% specificity). Serum levels of AGA-IgG and AGA-IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of the alpha-glucosidases (n = 1). CONCLUSIONS: This study confirmed the reliability and accuracy of EmA-IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA-positive patients in whom celiac disease is suspected.

Antibodies↗

Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors.

OBJECTIVE: Prophylactic therapies have demonstrated efficacy in reducing the incidence of deep venous thrombosis (DVT) in neurosurgical patients. Retrospective analysis of patients undergoing neurosurgical procedures at the University of Michigan demonstrated a high incidence (14%) of postoperative DVT among patients with intracranial neoplasms treated with sequential compression device (SCD) prophylaxis alone. Therefore, we investigated the efficacy and safety of the low-molecular weight heparin enoxaparin in preventing DVT in patients with brain tumors. The goal of the study was to compare SCD, enoxaparin, and combined SCD/enoxaparin prophylaxis among patients requiring surgery for treatment of intracranial neoplasms. METHODS: Eligible patients were randomized to SCD, enoxaparin, or combined therapy. Treatment was initiated before the induction of anesthesia and was continued throughout the hospital stay. Patients were screened for DVT, using duplex imaging, on four occasions in the first 1 month after surgery. The incidences of DVT and serious adverse events were compared between groups using analysis of variance and the Dunnet two-sided t test. RESULTS: Sixty-eight patients completed the study. Postoperative DVT occurred in 3 of 22 (13.6%) SCD-treated patients, 1 of 23 (4.3%) enoxaparin-treated patients, and 4 of 23 (17.4%) SCD/enoxaparin-treated patients. Differences were not statistically significant. Postoperative intracranial hemorrhage did not occur in patients in the SCD-treated group, whereas 5 of 46 patients receiving low-molecular weight heparin suffered clinically significant intracranial hemorrhage. The study was terminated because of the increased incidence of adverse events in the enoxaparin-treated groups. CONCLUSION: Enoxaparin therapy initiated at the time of anesthesia induction increases postoperative intracranial hemorrhage.

Adult↗

Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population.

OBJECTIVE: Increasing evidence suggests that nitric oxide participates in the pathophysiology of intestinal barrier function/dysfunction and inflammation. Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression have been observed in colonic mucosal biopsies of adults with inflammatory bowel disease (IBD). It is unclear whether iNOS induction is specific for IBD or a reflection of nonspecific mucosal inflammation. Furthermore, the characteristics of iNOS mRNA expression in pediatric patients with gastrointestinal disorders remains ill-defined. Our objective was to examine the relationship between iNOS mRNA expression and gastrointestinal mucosal inflammation in a pediatric population. METHODS: Esophageal and colonic mucosal biopsies were obtained during endoscopy. Total RNA was isolated from these biopsies and reverse transcription-polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp primers that amplified a predicted 372-bp conserved iNOS mRNA fragment. RESULTS: Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7-16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR amplification in six of 10 patients with ulcerative colitis and in two of four patients with Crohn disease. However, iNOS mRNA was not amplified in any esophageal biopsy or in rectal mucosa biopsies with normal histology. CONCLUSIONS: These data indicate that upregulation of iNOS mRNA expression in colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not upregulated in esophageal mucosa or in the absence of colonic inflammation. Further studies designed to determine the site- and cell-specificity of iNOS mRNA upregulation in mucosal biopsies from children with IBD may further illuminate the pathophysiology of these disorders.

Adolescent↗

Enhancement of fibronectin expression in rat lung by ozone and an inflammatory stimulus.

This study investigated the relationship of fibronectin expression and induction of pulmonary inflammation by ozone (O3). Rats were exposed to 0.8 parts/million O3 to induce lung inflammation. A second inflammatory stimulus, rabbit serum, was applied intratracheally to augment O3-induced inflammation. Bronchoalveolar lavage fluid (BALF) and lung tissues were analyzed for fibronectin protein and mRNA expression. Blood plasma was analyzed to investigate the potential of a minimally invasive procedure in predicting lung inflammation and fibronectin levels. Significant increases in the levels of fibronectin protein in the BALF and lung tissue after O3 exposure were further enhanced by pretreatment with normal serum. An increase in fibronectin mRNA following O3 exposure was also enhanced by serum pretreatment, which by itself had no effect on lung fibronectin mRNA expression. Plasma fibronectin levels were comparable in air-PBS and O3-PBS groups but increased in the O3-serum group. The results suggest leakage of fibronectin from blood plasma into the lung following intratracheal application of rabbit serum and upregulation of local synthesis following O3 exposure.

Animals↗

Comparative analgesic activity of nimesulide and diclofenac by intramuscular route: correlation with pharmacokinetic profile of nimesulide.

Nimesulide, a selective cyclooxygenase-2-inhibiting nonsteroidal anti-inflammatory drug, has been found to be a potent anti-inflammatory and analgesic drug, when administered orally, rectally or topically. The aim of the present study was to evaluate the comparative efficacy of intramuscularly injected nimesulide with that of diclofenac and to elucidate the pharmacokinetic profile of this formulation. Swiss albino mice were used in the experiment. Analgesic activity was tested using the acetic acid writhing test and the tail-flick latency test. Plasma levels of nimesulide and its active metabolite, hydroxynimesulide, were determined by a HPLC method. A peak analgesic effect was observed between 60 and 120 min, while Cmax (10.6 +/- 3.8 micrograms/ml) of nimesulide was reached at 60 min (Tmax). Analgesia was induced within 15 min of administration of nimesulide and was significantly higher than that of diclofenac at 90 and 120 min posttreatment in the writhing reflex and at 60 and 90 min in the tail-flick latency test. The results indicate that intramuscularly injected nimesulide may be an alternative mode of administration in uncooperative patients or when immediate analgesic effects are warranted.

Acetic Acid↗

Comparative analgesic efficacy of nimesulide and diclofenac gels after topical application on the skin.

Nimesulide is a newer non-steroidal anti-inflammatory drug (NSAID) with selective cyclo-oxygenase (COX)-2 blocking property and has demonstrated a potent analgesic and anti-inflammatory activity on oral and rectal administration. However, the Cmax through both these routes is reached only after 3 h of administration. Dose-dependent gastrointestinal side effects also limit the concentration of drug that can be achieved at the site of inflammation when administered through these routes. The present study was conducted to evaluate the antinociception induced by a new gel formulation of nimesulide when applied on the skin. Efficacy of topical nimesulide gel 1% (w/w) was studied on mice in the acetic-acid-induced writhing, tail flick latency (TFL) test and formalin-induced pain models. The antinociceptive effect of nimesulide was compared to diclofenac gel (1% w/w). Both the drugs induced dose-dependent analgesia with peak effect seen between 90 and 120 min after treatment. Greater antinociceptive effect (expressed as percent maximum possible effect) was seen in the writhing test than in the TFL test, indicating the peripheral action of both drugs. Nimesulide evidenced significant protection in the first phase of formalin-induced pain indicating modulation of peripheral nociceptors unlike other conventional NSAIDs. This suggests that COX-2 may be a primary contributor to afferent evoked increase in prostanoid-mediated changes in pain processing. Antinociception seen following drug application on the skin was lower than that seen on intraperitoneal administration, indicating localised action following topical application. The findings of the present study suggest that the transgel formulation of nimesulide provides significant analgesic activity when applied topically.

Administration, Topical↗

Ultrasound guided fine needle aspiration cytology in abdominal tuberculosis.

Although barium studies and CT are useful in assessing abdominal pathology in tuberculosis, imaging findings are not always specific and a histopathological or bacteriological confirmation is often required. The aim of the present study was to evaluate the role of ultrasound (US) guided fine needle aspiration cytology (FNAC) in the diagnosis of abdominal tuberculosis in patients with non-palpable lesions detected on US/CT. FNAC was performed on 31 sites in 30 patients. The sites included enlarged lymph nodes (n = 14), focal lesions in liver (n = 2) and spleen (n = 8), and thickened bowel in the ileocaecal region (n = 7). The results were classified cytomorphologically into four groups: (1) definite evidence of tuberculosis; (2) presumptive evidence of tuberculosis; (3) suggestive of tuberculosis; and (4) negative for tuberculosis. 18 of the 31 FNACs (58%) revealed a positive diagnosis of tuberculosis (definite evidence in nine patients and presumptive evidence in nine patients). 13 of the 31 FNACs (42%) showed either necrosis alone (n = 4) or negative results (n = 9). Zeihl-Neelson staining for acid-fast bacilli on direct smear was positive in only nine patients (29%). Splenic and lymph nodal FNAC had a high sensitivity (87.5% and 78.6%, respectively) in the diagnosis of tuberculosis. None of the bowel and liver FNACs was diagnostic. No complications were encountered. US guided FNAC offers a safe and accurate method of achieving a diagnosis in patients with suspected abdominal tuberculosis who present with radiologically demonstrable but non-palpable lesions, especially those involving lymph nodes and spleen.

Abdomen↗

Delayed manifestation of ultra violet radiation induced erythema in guinea pigs by sodium pyruvate--a free radical scavenger.

Sodium pyruvate, a free radical scavenger was evaluated for anti-inflammatory activity using UV radiation induced dermal erythema on guinea pig and compared with that of standard naproxen. Oral as well as topical pyruvate exhibited significant activity against UV induced dermal erythema model and the activity was comparable to that of naproxen. In the other pharmacodynamic studies, such as the studies on rat blood pressure, isolated guinea pig ileum and rat uterus, it showed no effect on any of these. In conclusion, sodium pyruvate showed a significant protection in the UV induced dermal erythema in guinea pigs. It also showed good absorption in UV-B range and this property can be utilised to develop the sodium pyruvate as a sunscreening agent.

Animals↗

Hepatosplenic tuberculosis: a cause of persistent fever during recovery from prolonged neutropenia.

SETTING: Hepatosplenic abscesses in neutropenic patients, especially during the recovery phase, are almost always attributed to fungal infections. We report similar lesions due to Mycobacterium tuberculosis in neutropenic patients in a tertiary care centre in India. OBJECTIVE: To characterize the features of hepatosplenic tuberculosis in neutropenic patients. DESIGN: Retrospective comparison of disease pattern and response to treatment of hepatosplenic tuberculosis in febrile neutropenia patients (four of 30 with severe prolonged neutropenia) and in non neutropenic patients diagnosed during the same 12-month period (n = 4, control group). RESULTS: The disease in the neutropenic patients typically presented during the recovery phase of neutropenia, with ultrasonic abnormalities similar to those seen in hepatosplenic fungal infections. In contrast to the marked organomegaly and typical granulomatous response found in the control group, the disease in the neutropenic patients was characterised by an absence of organomegaly, non-involvement of other sites, poor inflammatory response and a high bacillary load. The initial response to therapy was satisfactory in both groups. CONCLUSION: Tuberculosis needs to be considered in the diagnostic work-up of hepatosplenic abscesses that occur during the recovery phase of neutropenia.

Abscess↗

Observations on hepatic structure and function in fibro-calculous pancreatic diabetes (FCPD) vis-a-vis other diabetic subtypes.

Investigations of liver function and histology were undertaken in thirty four patients with Fibrocalculous Pancreatic Diabetes (FCPD). The data obtained were compared with those of similarly aged members of a diabetic control group comprising twelve patients with Protein Deficient Diabetes Mellitus (PDDM), twelve with Type 1 diabetes or Insulin Dependent Diabetes Mellitus (IDDM) and four young patients with Type 2 Diabetes of Non-Insulin Dependent Diabetes Mellitus (NIDDM). None of them had apparent past or present liver disease. Elevations of serum ALT (SGPT) and alkaline phosphatase levels were fairly common and was often associated with mild fatty changes and occasionally with focal necrosis and inflammatory changes. Cirrhosis and inflammatory changes per se were infrequent and fatty changes per se did not occur. In contrast patients belonging to the other diabetic subsets were very occasionally afflicted with hepatic abnormalities or not afflicted at all. We propose that loss of hepatotrophic actions mediated by insulin and glucagon could initiate and/or enhance hepatic abnormalities in FCPD where deficiencies of insulin and glucagon coexist.

Adolescent↗

The clinical behavior of breast carcinoma is probably determined at the preinvasive stage (ductal carcinoma in situ).

BACKGROUND: Mammography has greatly increased the number of women diagnosed with ductal carcinoma in situ (DCIS) of the breast. New classifications of DCIS recently have been proposed. In this study, these classifications were applied to DCIS associated with invasive tumors and correlated with patient prognosis. METHODS: Three hundred cases of infiltrating ductal carcinoma of the breast in which there was associated DCIS in the surrounding breast were studied. The DCIS was classified as well, moderately, or poorly differentiated, according to two recently published systems using the cytonuclear features of the malignant cells (Holland classification) and cytology and the presence of necrosis (Van Nuys classification). RESULTS: The differentiation of DCIS was significantly correlated with the grade of the invasive carcinoma (P < 0.0001), the Nottingham prognostic index (P < 0.0001), and the clinical outcomes of the patients (P < 0.0001). CONCLUSIONS: These findings indicate that a model in which there is increasing in situ dysplasia before the development of stromal invasion is incorrect for breast carcinoma. Rather, in most cases, well-differentiated DCIS probably gives rise to low grade invasive breast carcinoma with a better long term clinical outcome. These data suggest that many of the important prognostic biologic and genetic characteristics of breast carcinoma are already established in the neoplastic clones of malignant cells at the preinvasive stage of the disease.

Breast Neoplasms↗