The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy.

The mechanisms involved in the weight loss seen after vertical sleeve gastrectomy (VSG) are not clear. The rat stomach has two morphologically and functionally distinct proximal and distal parts. The rat model for VSG involves complete removal of the proximal part and 80% removal of the distal part along the greater curvature. The purpose of this study was to understand the potential independent contributions of removal of these distinct gastric sections to VSG outcomes. We prepared four surgical groups of male Long-Evans rats: VSG, sham surgery (control), selective proximal section removal (PR), and selective distal section removal (DR). Gastric emptying rate (GER) was highest after VSG compared with all other groups. However, PR, in turn, had significantly greater GER compared with both DR and sham groups. The surgery-induced weight loss followed the same pattern with VSG causing the greatest weight loss and PR having greater weight loss compared with DR and sham groups. The results were robust for rats fed regular chow or a high-fat diet. Body mass analysis revealed that the weight loss was due to the loss of fat mass, and there was no change in lean mass after the surgeries. In conclusion, removal of the proximal stomach contributes to most, but not all, of the physiological impact of VSG.

Lingual lipase activity in the orosensory detection of fat by humans.

Lingual lipase generates nonesterified fatty acids (NEFA) from dietary fats during oral processing by lipolysis. Lingual lipase in rodents has strong lipolytic activity and plays a critical role in oral detection of fats. The functional activity of lingual lipase during oral processing of high-fat foods in humans remains poorly characterized. Five commonly consumed high-fat foods varying in physical states and fatty acid composition (almond, almond butter, olive oil, walnut, and coconut) were masticated by 15 healthy human subjects at the rate of one chew per second with and without lipase inhibitor orlistat. Salivary NEFA concentrations were measured. To determine the role of lingual lipase in oral fat detection, sensory ratings were obtained from the same 15 human subjects for almond butter with and without orlistat. Lingual lipase was active during oral processing of almond and coconut. No activity of lingual lipase was detected during processing of almond butter. There was only weak evidence lingual lipase is a determinant of oral fat detection. Lingual lipase may only contribute to NEFA generation and oral fat detection of fatty foods that require stronger oral processing effort.

Plakoglobin regulates cell motility through Rho- and fibronectin-dependent Src signaling.

We previously showed that the cell-cell junction protein plakoglobin (PG) not only suppresses motility of keratinocytes in contact with each other, but also, unexpectedly, of single cells. Here we show that PG deficiency results in extracellular matrix (ECM)-dependent disruption of mature focal adhesions and cortical actin organization. Plating PG⁻/⁻ cells onto ECM deposited by PG+/⁻ cells partially restored normal cell morphology and inhibited PG⁻/⁻ cell motility. In over 70 adhesion molecules whose expression we previously showed to be altered in PG⁻/⁻ cells, a substantial decrease in fibronectin (FN) in PG⁻/⁻ cells stood out. Re-introduction of PG into PG⁻/⁻ cells restored FN expression, and keratinocyte motility was reversed by plating PG⁻/⁻ cells onto FN. Somewhat surprisingly, based on previously reported roles for PG in regulating gene transcription, PG-null cells exhibited an increase, not a decrease, in FN promoter activity. Instead, PG was required for maintenance of FN mRNA stability. PG⁻/⁻ cells exhibited an increase in activated Src, one of the kinases controlled by FN, a phenotype reversed by plating PG⁻/⁻ cells on ECM deposited by PG+/⁻ keratinocytes. PG⁻/⁻ cells also exhibited Src-independent activation of the small GTPases Rac1 and RhoA. Both Src and RhoA inhibition attenuated PG⁻/⁻ keratinocyte motility. We propose a novel role for PG in regulating cell motility through distinct ECM-Src and RhoGTPase-dependent pathways, influenced in part by PG-dependent regulation of FN mRNA stability.

Detection of differentially expressed basal cell proteins by mass spectrometry.

The ability of cells to modulate interactions with each other and the substrate is essential for epithelial tissue remodeling during processes such as wound healing and tumor progression. However, despite strides made in the field of proteomics, proteins involved in adhesion have been difficult to study. Here, we report a method for the enrichment and analysis of proteins associated with the basal surface of the cell and its underlying matrix. The enrichment involves deroofing the cells with 20 mM ammonium hydroxide and the removal of cytosolic and organellar proteins by stringent water wash. Proteomic profiling was achieved by LC-FTMS, which allowed comparison of differentially expressed or shared proteins under different cell states. First, we analyzed and compared the basal cell components of mouse keratinocytes lacking the cell-cell junction molecule plakoglobin with their control counterparts. Changes in the molecules involved in motility and invasion were detected in plakoglobin-deficient cells, including decreased detection of fibronectin, integrin beta(4), and FAT tumor suppressor. Second, we assessed the differences in basal cell components between two human oral squamous cell carcinoma lines originating from different sites in the oral cavity (CAL33 and UM-SCC-1). The data show differences between the two lines in the type and abundance of proteins specific to cell adhesion, migration, and angiogenesis. Therefore, the method described here has the potential to serve as a platform to assess proteomic changes in basal cell components including extracellular and adhesion-specific proteins involved in wound healing, cancer, and chronic and acquired adhesion-related disorders.

Persistence, dissipation and consumer risk assessment of a combination formulation of flubendiamide and deltamethrin on cucumber.

Multi-location supervised field trials were conducted in India at four locations of the All India Network Project (AINP) on Pesticide Residues to study the persistence, dissipation and risk assessment of flubendiamide and deltamethrin on cucumber (Cucumis sativus). Residues of flubendiamide and deltamethrin on cucumber resulting from three spray applications of a combination formulation (flubendiamide 90% + deltamethrin 60%, 150 SC) at recommended (22.5 + 15 g a.i./ha) and double the recommended (45 + 30 g a.i./ha) dose were analysed. On the basis of persistence and dissipation studies, the half- life (T1/2) of flubendiamide on cucumber varied from 1.40 to 2.98 (recommended dose) and 1.55 to 2.76 days (double the recommended dose), while that of deltamethrin ranged from 2.5 to 4.9 (recommended dose) and 2.7 to 3.9 days (double the recommended dose) at the four locations. On the basis of supervised field trial data and using OECD calculator, MRLs in the combination product of 3 mg kg-1 for flubendiamide and 1.5 mg kg-1 for deltamethrin has been proposed for consideration by the Food Safety and Standards Authority of India (FSSAI). Codex, EU and EPA have fixed MRL of 0.2 mg kg-1 for flubendiamide and deltamethrin.

Parotid TB.

TB of the parotid is rare and only about 100 cases have been reported in the world literature. Often the diagnosis is made only after the surgery performed for a suspected neoplasm. We describe three patients with diffuse form of parotidTB without any evidence of tubercular focus elsewhere. Fine needle aspiration cytology confirmed the diagnosis in two cases, while the third case was diagnosed only after surgery.

Accuracy of palpation, ultrasonography, and computed tomography in the evaluation of metastatic cervical lymph nodes in head and neck cancer.

INTRODUCTION: India accounts for the majority of oral cancer cases occurring worldwide. The metastasis of oral cancer to the regional lymph nodes and distant sites determines the prognosis and the survival rate of this disease. OBJECTIVES: The aim and objectives of this study were to evaluate the accuracy of preoperative clinical methods such as palpation, ultrasonography (USG), and computed tomography (CT) in comparison with postoperative histopathological findings in determination of metastatic cervical lymph nodes and also to assess whether combining these techniques increases the specificity and sensitivity of lymph node metastasis in oral squamous cell carcinoma (SCC). METHODOLOGY: Totally, 26 consecutive biopsy proven cases of oral SCC were included, and the nodal status was evaluated by palpation, CT and ultrasound (US) and confirmed by histopathological examination. The results were presented in terms of sensitivity, specificity, predictive values, accuracy, and P value. RESULTS: Palpation, USG, and CT findings were compared with histopathologic findings by Fisher's exact test and the "P" value for palpation, US and CT were 0.003, 0.000, 0.000, respectively, which are statistically significant. CONCLUSION: US examination combined with CT gives a better assessment of the neck for nodal metastasis.

Steroid response to adrenocorticotropin stimulation in children with human immunodeficiency virus infection.

To evaluate whether frank or subtle disorders of adrenal steroidogenesis exist in human immunodeficiency virus (HIV)-infected children, the adrenal steroid response to an iv bolus of ACTH-(1-24) (0.25 mg Cortrosyn) was determined. Ten children (six males and four females, aged 7 months to 7.5 yr) were studied. Five underwent repeat testing 3-5 months after initial assessment. Nine patients were classified as P2 or symptomatic according to the Center for Disease Control criteria for HIV infection in children. Eight had failure to thrive, six had opportunistic infections and neurological deficits, and two were receiving ketoconazole at the time of ACTH testing. Only one patient had a neonatally acquired transfusion-related HIV infection. Three of the children died 2-5 months after ACTH testing. All patients had normal or slightly elevated baseline and stimulated cortisol levels compared to the control population. The mean post-ACTH cortisol level was significantly higher than the mean post-ACTH level in the control population. No patient demonstrated an impaired aldosterone response to ACTH. The basal and ACTH-stimulated dehydroepiandrosterone levels were normal. Although individual deoxycorticosterone and corticosterone levels were variable, the mean stimulated deoxycorticosterone and corticosterone levels in the patients were suggestive of a selective defect of the 17-desoxy pathway in the adrenal fasciculata. No changes were noted in the patients' cortisol, dehydroepiandrosterone, and aldosterone responses on repeat ACTH testing. In HIV-infected children we have demonstrated that cortisol and aldosterone synthesis is intact. Thus, the chronic debilitation observed cannot be explained on the basis of adrenal insufficiency. However, a selective deficiency of 17-desoxysteroid hormone production from the adrenal fasciculata may be present.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives.

Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1, 3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.

Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl-containing thiazolidinediones.

A series of substituted pyridyl- and quinolinyl-containing 2, 4-thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPARgamma by 5a/5a maleate did not show any significant transactivation of PPARalpha or PPARgamma.

Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones.

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.

Novel euglycemic and hypolipidemic agents. 1.

A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.

Impact of improved survival of very low birth weight infants on recent secular trends in the prevalence of cerebral palsy.

OBJECTIVE: To review recent secular trends in the prevalence of cerebral palsy in industrialized countries that have population-based cerebral palsy registries and to estimate such time-trends for the United States, where until recently such registries were absent. DATA SOURCES: Recent epidemiologic studies of cerebral palsy published in peer-reviewed journals in English, and US vital data bearing on the principal demographic determinants of cerebral palsy--birth rates, the birth weight distributions, birth weight-specific mortality risk, and cerebral palsy risk among survivors. RESULTS: Most epidemiologic studies from industrialized countries show a rise in the childhood prevalence of cerebral palsy in recent decades, largely because of the increasing contribution of children of low and very low birth weight to its prevalence. The only demographic determinant of cerebral palsy prevalence that is changing rapidly in the United States is survival of low birth weight and very low birth weight infants. Based on the magnitude of change in the survival of low and very low birth weight infants, it is estimated that childhood prevalence of cerebral palsy rose about 20% between 1960 and 1986 in the United States. CONCLUSION: An apparently unavoidable side effect of the increasing success of newborn intensive care is a moderate rise in the childhood prevalence of cerebral palsy.

The reliability of neonatal head circumference measurement.

Interobserver reliability in head circumference measurement was assessed in a cohort of 1105 low birthweight (less than or equal to 2000 g) infants enrolled in a study of brain hemorrhage. In 927 (83.9%) subjects, head circumference was measured both by a pediatric resident or admitting pediatrician, and by a trained ultrasound technologist. The Pearson correlation coefficient for these two sets of measurements was 0.934 (p less than 0.01), and the intraclass correlation coefficient was 0.933. By contrast, analysis of differences revealed that the limits of agreement were from -1.99 to 2.03 cm, indicating that 5% of measurements differed by 2 cm or more. Using clinicians' measurements as the gold standard, ultrasound technologists detected abnormal head circumferences with a sensitivity of 91.2%, a specificity of 97.2%, and a positive predictive value of 88.0%. For clinical purposes this level of reliability may be acceptable, but in research studies this degree of misclassification would lead to attenuation of the odds ratio.

Clinical and biochemical changes in chronically exposed organophosphate workers.

Health effects of occupational organophosphate exposure were investigated by subjecting 22 workers chronically exposed to an organophosphate pesticide, fenthion (O,O-dimethyl-O-(4-methylmercapto-3-methylphenyl)-phosphorothioate) to clinical evaluation, estimation of serum cholinesterase, serum alkaline phosphatase (SAP), serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The mean age of the workers was 31 years and the mean duration of fenthion exposure 8.2 years. Headache (59%), giddiness (50%), ocular symptoms (27%) and paresthesia (18%) were the commonest symptoms. Serum acetylcholinesterase and butyrylcholinesterase levels were significantly lower than in controls. After withdrawing the workers from organophosphate exposure for 3 weeks, the follow-up study revealed absence of transient symptoms. There was no change in their neurological status, and serum acetylcholinesterase and butyrylcholinesterase levels were raised significantly, whereas the other serum enzymes showed no significant change. For monitoring of occupational organophosphate exposure, the importance of both clinical and biochemical parameters is emphasised.

Impact of the Integrated Child Development Services in Uttar Pradesh.

PIP: Impact of the Integrated Child Development Services (ICDS) scheme in the district Rae Bareli of Uttar Pradesh was studied by assessing changes in feeding practices, growth and development, prevalence of malnutrition, and utilization of health care services using a suitable control population from a non-ICDS area. Breastfeeding was almost universal and there was no significant difference in breastfeeding patterns. In the study area, 55.3% of the children were weaned between 6-12 months while the majority (53.1%) in the control group were weaned at ages 12-18 months (P0.001). Weight for age was significantly higher in ICDS group males (age 6 months-3 years) and female children (2-4 years). Milestones of development were comparatively delayed in the non-ICDS group. Prevalence rate for severe degrees of PEM (grades III and IV) was 3.2/100 in the ICDS group and 14.8/100 in the control group (P0.001). Immunization status of children in the study group, though much higher than in the control group, was not up to the desired level. Mothers of 61.3% of the children in the ICDS group and only 19.9% of the control group availed themselves of antenatal care services (P0.001). Domiciliary delivery was almost universal (96.3 and 97.4%) but utilization of services of trained dai of ANM was significantly more in the ECDS group (P0.001). Only 14% of the children in the ICDS group were benefitted by the supplementary nutrition services, whereas the utilization of primary healthcare facilities was greater in the ICDS group (P0.001).^ieng

Transfusion associated HIV infection in patients with haematologic disorders in southern India.

Seventy patients with congenital coagulation disorders (group A) and 202 other patients (group B) attending the Haematology clinic at the Christian Medical College and Hospital, Vellore (India) were screened for HIV infection between March 1989 and April 1991. Fifty five patients in group A and 131 patients in group B had received blood or blood products in the past. Nineteen transfused patients (9 in group A and 10 in group B) had received blood or blood products exclusively from the hospital blood bank and none of them was HIV infected. Among the remaining 167 transfused patients, 14 (30.4%) of the 46 patients in group A and 6 (4.9%) of the 121 patients in group B were found to be positive for HIV. In group A, 13 of the 14 infected patients had received commercially available cryoprecipitate which was thus found to be the most frequent source of infection. In group B the source of infection was most probably unscreened HIV infected blood which was transfused.

Validated HPLC method for determination of PAT-5A, an insulin sensitizing agent, in rat plasma.

A high performance liquid chromatographic method for the determination of PAT-5A (a potent insulin sensitizer) using DRF-2095 (a thiazolidinedione) as internal standard (I.S.) is described. A 1:1 v/v ethylacetate and dichloromethane solvent mixture was used for extraction of PAT-5A from plasma. A Kromasil KR100-5C18-250A, 5 microm, 4.6 x 250 mm SS column was used for the analysis. Mobile phase consisting of sodium dihydrogen phosphate (pH 4.0, 0.05 M) and methanol mixture (25:75, v/v) was used at a flow rate of 1.0 ml/min. The eluate was monitored using a UV detector set at 345 nm. Ratio of peak area of analyte to I.S. was used for quantification of plasma samples. Using this method the absolute recovery of PAT-5A from rat plasma was > 90% and the limit of quantification was 0.05 microg/ml. The intra-day relative standard deviation (RSD) ranged from 2.19 to 4.98% at 1.0 microg/ml, 1.05 to 3.68% at 10.0 microg/ml and 3.14 to 5.08% at 50 microg/ml. The inter-day RSD were 1.6, 2.24 and 1.54% at 1, 10 and 50 microg/ml, respectively. The method was applied to measure the plasma concentrations of PAT-5A in pharmacokinetic and bioavailability studies in male Wistar rats.

Surgery in patients with congenital coagulation disorders.

BACKGROUND: Surgery is occasionally necessary in patients with congenital coagulation disorders. Major surgery for patients with haemophilia was not being done in India until recently. This paper reports the experience of a single referral centre. METHODS: The data of 52 patients who were operated upon were collected from the hospital records retrospectively between 1984 and 1986 and prospectively thereafter. They included the surgical procedure performed, replacement therapy used and complications encountered. RESULTS: Fifty-nine procedures were performed of which 26 were major, 30 minor and 3 were diagnostic angiograms. Blood components produced in the hospital blood bank were commonly used for replacement and primary haemostasis was achieved in all patients. Delayed bleeding due to inadequate factor levels occurred in 12 procedures and was controlled by increasing the factor replacement. One patient died of suspected acute myocardial ischaemia. CONCLUSION: In India surgical procedures can be safely performed in patients with congenital coagulation disorders.