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Biomedical subjects

S Bhatnagar

Publications and source records attributed to S Bhatnagar.

At least 55 records · Page 3Linked to original sources
PubMed1999

Serological diagnosis of celiac disease.

In developing countries like India, unlike in the West, diagnosis of celiac disease is a dilemma because the histological changes consistent with celiac disease may not be pathognomonic of the disease. We need clarity on how to use one or more of the serological antibodies, namely IgG and IgA anti-gliadin and IgA anti-endomysial antibodies as independent disease markers or as adjuncts to clinico-histological diagnosis. In this review, various possible algorithms have been discussed. The serological antibodies can be used as reliable screening tests to decide whom to biopsy and to interpret histological changes in our settings where malnutrition and intercurrent enteric infection are common.

Antibodies, Anti-Idiotypic↗
PubMed1998

The effects of prior chronic stress on cardiovascular responses to acute restraint and formalin injection.

Exposure to acute stressors activates both the hypothalamic-pituitary-adrenal (HPA) and cardiovascular systems. Prior chronic stress enhances HPA responses to novel, acute stressors, but whether it alters cardiovascular responsivity to novel, acute stress is unknown. In the present study, we examined mean arterial blood pressure (MAP) and heart rate (HR) to two distinct stimuli, restraint and formalin, following prior exposure to 7 days of intermittent cold. In two sets of control and chronically stressed animals, we measured MAP and HR for 60 min following onset of 30 min restraint and MAP, HR and behavioral responses to intraplantar injection of formalin. Chronic stress raised MAP and HR under resting conditions and elevated HR during, but not following termination of, restraint. These increases in HR during restraint were due to the differences in resting levels of HR, since both control and chronically stressed animals exhibited similar increases from resting levels in HR during restraint. Conversely, chronically stressed animals exhibited lower changes in MAP and HR from resting levels following termination of restraint. Formalin produced the characteristic biphasic pattern of cardiovascular and behavioral responses. Prior chronic stress did not alter behavior, but increased MAP and HR in Interphase and only MAP in Phase 2. The increases in MAP during Interphase and Phase 2 were a result of the elevations in resting levels of MAP, but even when differences in resting levels were taken into account, HR remained elevated in the Interphase in chronically stressed animals. Together, these data demonstrate that prior chronic intermittent cold stress modifies cardiovascular function both under resting conditions and, in very specific ways, under stimulated conditions produced by restraint and formalin. We propose that these modifications are produced by brain regions that are known to regulate cardiovascular function and which are activated by chronic stress.

Adrenocorticotropic Hormone↗
PubMed1998

Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children.

We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.

Acute Disease↗
PubMed1998

Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress.

Animals exposed to chronic stress exhibit normal or enhanced hypothalamic-pituitary adrenal responses to novel, acute stimuli despite the inhibitory endogenous corticosteroid response to the chronic stressor. Prior stress is thought to induce a central facilitatory trace that, upon exposure to a novel stimulus, balances or overcomes the inhibitory effects of corticosterone. The neuroanatomical basis for this facilitation of hypothalamic pituitary adrenal responses is unknown. In this study, we first show increased adrenocorticotropin and corticosterone responses to the novel stressor of restraint in rats exposed to intermittent cold for seven days. We then compared numbers of Fos-immunoreactive cells in 26 sites in control and chronically stressed rats at various times after onset of a 30 min restraint. At 60 min, density of Fos-stained cells was significantly higher in chronically stressed than in control rats in the parabrachial/Kölliker-Fuse area, posterior paraventricular thalamus, central, basolateral and basomedial nuclei of the amygdala and parvocellular paraventricular hypothalamus. The posterior paraventricular nucleus of the thalamus receives projections from the parabrachial nucleus and projects heavily to the differentially stained subnuclei of the amygdala, which in turn project to the parvocellular paraventricular nucleus of the hypothalamus. We propose that increased activity in the parabrachial-posterior paraventricular thalamus-amygdala-parvocellular paraventricular hypothalamus underlies facilitation of the hypothalamic pituitary-adrenal axis to novel stress in chronically stressed rats. We confirmed part of this proposal by showing that lesions of the posterior paraventricular nucleus of the thalamus increase adrenocorticotropin responses to restraint only in previously chronically stressed animals. This potential circuit provides a basis for further examination of the functional roles of these regions in stress-induced facilitation of hypothalamic pituitary-adrenal activity.

Adrenocorticotropic Hormone↗
PubMed1998

The effects of intrahippocampal scopolamine infusions on anxiety in rats as measured by the black-white box test.

Hippocampal cholinergic projections mediate attention to arousing stimuli as demonstrated by behavioral, electrophysiological, and endocrine studies. We recently reported that peripheral injections of the cholinergic antagonist scopolamine (SCOP) increased anxiety-like behaviour (ALB) in rats and we sought to investigate if this response might be hippocampally mediated. Adult male, Lister Hooded rats were implanted bilaterally with hippocampal cannulae 3 weeks prior to testing. On the test day, rats were injected with vehicle (VEH; artificial CSF at 3 microl), 15 or 30 microg SCOP, 20 min prior to being placed into the white chamber of the black-white box (n = 10/group). Rats were scored for latencies to exit and reenter the white chamber, total time spent in the white chamber, intercompartmental crossings, and activity. SCOP at 30 microg significantly reduced time to exit the white arena, while both doses of SCOP elevated latencies to reenter the white chamber. There were no effects of SCOP on intercompartmental crossing, time spent in the white chamber, or on activity levels. Loss of hippocampal cholinergic function impairs processing of threatening stimuli that manifests itself as increased ALB.

Analysis of Variance↗
PubMed1998

IgD myeloma with multiple cutaneous plasmacytomas.

Extramedullary cutaneous plasmacytoma is an uncommon observation in clinical practice. In most of the cases it is usually an extension of underlying medullary plasmacytoma. This case report describes a patient with IgD myeloma who went into plateau phase following standard intravenous chemotherapy. After more than a year in plateau phase, he developed multiple fleshy nodular lesions in the skin. Biopsy of one of the lesions revealed relapse of myeloma in the skin. His IgD paraprotein remained in plateau phase and the bone marrow showed only 1% plasma cells. The patient has been treated with systemic intravenous chemotherapy followed by local radiotherapy.

Aged↗
PubMed1998

Schwannoma with features mimicking neuroblastoma: report of two cases with immunohistochemical and ultrastructural findings.

OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET). METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by tinctorial stains and immunohistochemistry, and the tissue retrieved from formalin was examined by electronmicroscopy in one case. RESULTS: The tumours were small and subcutaneous. Both showed features of benign schwannoma; one had a multinodular plexiform pattern. In addition, rosette-like structures consisting of collagenous cores surrounded by small round cells or slightly larger epithelioid cells were present. Tumour cells were positive for S100 protein, Leu7, and in one case GFAP, but were negative for neurofilament protein, synaptophysin, and MIC2. Type IV collagen surrounded individual cells. Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes) and failed to show features of neuroblastoma (neuroendocrine granules). CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only and eliminated neuroblastoma/PNET. These uncommon variants should be recognised by practising histopathologists to avoid erroneous diagnoses and inappropriate treatment.

Adult↗
PubMed1997

Hippocampal cholinergic blockade enhances hypothalamic-pituitary-adrenal responses to stress.

We examined the role of the hippocampal cholinergic system, which is known to mediate processes related to fear and anxiety, in the regulation of stress-induced hypothalamic-pituitary-adrenal (HPA) activity. Bilateral intra-hippocampal injections (30 microg per side) of the muscarinic antagonist Scopolamine augmented adrenocorticotropin and corticosterone responses to restraint without altering basal HPA activity compared to vehicle-treated animals. These results suggest that the hippocampal cholinergic system regulates stress-induced HPA activity and may serve to coordinate behavioral and neuroendocrine responses to stress.

Adrenocorticotropic Hormone↗
PubMed1997

Structural characteristics of corn starches extruded with soy protein isolate or wheat gluten.

Commercially available corn starches containing 0, 25, 50 and 70% amylose were extruded with 10, 20 and 30% soy protein isolate (SPI) or wheat gluten (WG) at 22% moisture content (dry basis) in a C.W. Brabender single screw laboratory extruder using a 140 degrees C barrel temperature and a 140 rpm screw speed. True, solid and bulk densities; percent total, closed and open pores; and shear strengths of the extrudates were determined. The microstructures of the extrudates were studied by scanning electron microscopy (SEM). The total pores of the extrudates were affected significantly (p > F = 0.0001) by type of protein (SPI or WG) and starch amylose. The open or closed pores, were affected by protein type only. The interaction between amylose and protein contents was highly significant (p > F = 0.0001). In general, the total pores and bulk densities were higher for WG-starch extrudates compared to SPI-starch extrudates. These values decreased as amylose content increased from 0 to 25% and then increased thereafter. The open pores, on the other hand, increased with increasing protein content from 10 to 20% and then decreased. Extrudates containing WG had higher shear strengths than those containing SPI.

Amylose↗
PubMed1997

Antifilarial activity of a synthetic marine alkaloid, aplysinopsin (CDRI Compound 92/138).

CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post-infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250 mg/kg, p.o. The compound was active in vitro at 100 micrograms/ml concentration and caused a significant decline in MTT reduction and 14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.

Animals↗
PubMed1997

Effect of estrogen deprivation on the reproductive physiology of male and female primates.

The availability of CGS 16949A, CGS 20267 and CGP 47645, a series of aromatase inhibitors (AIs) having high specific activity and specificity, made possible this study wherein the need for estrogen (E) for regulating (a) follicular maturation/ovulation, luteal function and pregnancy establishment, and (b) testicular function of the bonnet monkey (Macaca radiata) has been examined. Generally these compounds, used in the range of 500 microg to 2.5 mg/day did not inhibit follicular maturation although they did reduce E levels. Although low doses had no effect on ovulation it appears that relatively high doses of CGS 20267 and CGP 47645 could be inhibiting it. Three oral doses of letrozole (CGS 20267, each dose of 2 mg) during the follicular phase resulted in the formation of multiple follicles in cycling females, and these could be ovulated by exogenous hCG (1000 IU) treatment. Although administration of AI during the early luteal phase had no effect on progesterone (P) production, it prevented pregnancy establishment. Whereas AI administration in the female had no significant effect on luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (except at high drug dosages), it significantly increased serum testosterone (T) levels in the male. Sustained high levels of T (30-50 ng/ml) could be maintained for 100 days by administering 2.5 mg of CGP 47465 orally once in 5 days. Blockade of E synthesis in the male led to the disruption of testicular germ cell transformation, which in turn resulted in a significant reduction in sperm production. These studies with aromatase inhibitors in the monkey suggest that these compounds have a potential for use as fertility regulating agents in both the male and female primate.

Animals↗
PubMed1996

Plaque-forming cell responses and antibody titers following injection of sheep red blood cells in nonstressed, acute, and/or chronically stressed handled and nonhandled animals.

Given the bidirectional nature of the communication between the immune and hypothalamic-pituitary-adrenal (HPA) systems, we examined whether animals that exhibit differences in HPA responses to stress would also exhibit differences in their plaque-forming cell (PFC) responses to sheep red blood cells (SRBC). Neonatally handled (H) animals exhibit lower HPA responses to a number of acute stressors in adulthood compared to nonhandled (NH) animals. Furthermore, these differences also emerge as a function of chronic, intermittent cold stress. We hypothesized that H and NH animals may exhibit differences in the PFC response to SRBC under conditions of acute and/or chronic stress (H CHR and NH CHR). Exposure to acute (4 hr) cold decreased PFC responses in both H and NH animals compared to nonstressed H and NH animals. The decrease in PFC response produced by chronic, intermittent cold stress was similar in H and NH animals and was not different from that found in acutely stressed animals. In H CHR animals reexposed to cold stress, the PFC response was not different from acutely stressed or chronically stressed H and NH animals. In contrast, the PFC response in NH CHR animals reexposed to cold stress was lower than all other groups studied. Thus, neonatal handling prevented prior chronic stress-induced suppression of the PFC response to a subsequent stress. These data suggest that there may be subpopulations of individuals in whom prior chronic stress does not exacerbate the immune suppression produced by acute stress. However, those chronically stressed individuals in whom immune suppression does occur may be more vulnerable to infection and disease.

Aging↗
PubMed1996

Muscarinic antagonists are anxiogenic in rats tested in the black-white box.

Central cholinergic (ACh) projections have been shown to modulate stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and are integral to the expression of electrophysiological correlates of arousal, namely hippocampal theta rhythm. The degree to which these actions of ACh are behaviorally relevant has received comparatively less attention, and we sought to investigate if manipulations of ACh systems might also affect behaviors related to stress and arousal. We chose to examine indices of anxiety as revealed by changes in behavior elicited by the black-white box test, a relatively novel and recently validated model of rodent anxiety. Groups of rats were injected with either scopolamine hydrobromide (SCOP; 0, 0.05, and 0.10 mg/kg i.p.) or the peripherally acting scopolamine methyl bromide (methyl-SCOP; 0, 0.05, and 0.10 mg/kg i.p.) to compare and contrast the effects of central and peripheral ACh blockade on measures of anxiety. SCOP pretreatment significantly lowered latencies for rats to escape from the white to black compartment, while methyl-SCOP elevated latencies to reenter the white chamber from the black. Both drugs increased the amount of time rats spent in the black compartment and also suppressed exploration as revealed by decreased episodes of intercompartmental locomotion. Neither drug deleteriously affected locomotor activity, however; in fact, SCOP significantly increased locomotion in the white chamber. In the absence of motor disturbances to account for any group differences, we contend that both central and peripheral ACh blockade may affect measures of anxiety, perhaps by directly or indirectly affecting HPA activity. Central ACh systems may underlie sensory filtering whereby irrelevant stimuli are excluded from sensory processing. Antagonism of ACh transmission may render an animal incapable of correctly processing sensory information leading to hyperresponsiveness, which can manifest itself as enhanced anxiety and fear.

Animals↗
PubMed1996

Reactive nitrogen intermediates production from naive and activated monocytes by extracts of Mycobacterium bovis BCG.

Extracts of Mycobacterium bovis strain BCG were assessed for in vitro activation of monocytes to produce reactive nitrogen intermediates. The culture filtrate of M. bovis BCG was a strong inducer of nitrite production while live BCG and sonicated antigens were also potent inducers. Other extracts activated monocytes which showed an increase in nitrite production after in vitro BCG infection.

Animals↗
PubMed1996

Prognostic factors in hospitalized children with persistent diarrhea: implications for diet therapy.

A dietary algorithm for management of persistent diarrhea in developing countries, using locally available foods, is yet to be standardized. We identified factors related to poor outcome among 75 malnourished hospitalized male patients aged 3-48 months with persistent diarrhea (> or = 14 days) treated on soy and cereal-based diet (Diet I). The 28 patients with stool output > 60 g/k body weight on the sixth or the seventh treatment day were considered diarrhea treatment failures on Diet I. In the univariate analysis, breast feeding (p < 0.001), carbohydrate malabsorption based on low stool pH or reducing substances > 0.5% (p = 0.03), initial 24-h purge rate (p = 0.001), pneumonia (p = 0.003), or probable septicemia (p = 0.03) were associated with diarrhea treatment failures. Although 16 of these 28 patients responded to systemic antibiotics without dietary modification, all but one of the remaining recovered on a chicken puree, glucose, and oil formulation. Twenty-six children had weight loss after 7 days on Diet I as compared with the postrehydration weight. These children had lower mean age (p = 0.05), lower food intake in the first 24 h (p = 0.05) and during the initial 7 days (p < 0.01), and a higher initial excretion of enteroaggregative Escherichia coli (32 vs. 8%; p = 0.01). In the logistic regression model, significant risk factors for diarrhea treatment failures were initial purge rates, carbohydrate malabsorption, and intercurrent systemic infection; only low food intake was associated with significant risk for weight loss. The significant association of diarrhea treatment failures with carbohydrate malabsorption suggests that in the initial diet itself, part of polysaccharide be substituted with sucrose or glucose to obtain the right balance between osmolarity and energy density. Our data suggest that prompt identification and treatment of systemic infection is critical, as its eradication achieved recovery in more than half of the treatment failures without a dietary change.

Algorithms↗
PubMed1996

Clamped Corticosterone (B) Reveals the Effect of Endogenous B on Both Facilitated Responsivity to Acute Restraint and Metabolic Responses to Chronic Stress.

To determine the effects of both corticosterone (B) and chronic stressors on acute ACTH responses to restraint, young male rats were exposed to streptozotocin-induced diabetes, cold (5-7 degreesC) or intracerebroventricular (icv) neuropeptide Y (NPY) for 5 d and then exposed to restraint within 2 h after lights on. Two groups of rats were studied: intact and adrenalectomized replaced with B pellets that maintained plasma B in the normal mean 24-h range of intact rats. In addition to ACTH and B responses to restraint on d 5, body weight, food intake, fat depots, glucose and other hormones were measured to determine the role of stress-induced elevations in B on energy balance. ACTH responses to restraint were normal in intact rats subjected to diabetes or cold. By contrast, there was no ACTH or B response to restraint in NPY-infused intact rats. All 3 groups of chronically stimulated adrenalectomized rats with clamped B had facilitated ACTH responses to restraint compared to their treatment controls. Overall food intake increased in all groups of stressed rats; however, augmented intake occurred only during the light in intact rats and equally in the light and dark in B-clamped rats. White adipose depot weights were decreased by both diabetes and cold and increased by NPY in intact rats; the decreases with cold and increases with NPY were both blunted and changes in fat stores were not significant in adrenalectomized, B-clamped rats. We conclude that: 1. diabetes- and cold-induced facilitation of restraint-induced afferent input to hypothalamic control of the hypothalamo-pituitary-adrenal (HPA) axis is opposed in intact rats by the elevated feedback signal of B secretion; 2. NPY does not induce facilitation of afferent stress pathways; 3. chronic stimulation of the HPA axis induces acute hyperresponsiveness of hypothalamic neurons to restraint provided that the afferent input of this acute stimulus is not prevented by B feedback; 4. stimulus-induced elevations in B secretion result in day-time feeding; 5. insensitivity of both caloric efficiency and white fat stores to chronic stress in adrenalectomized, B-clamped rats results from loss of normally variable B levels.

Journal Article↗
PubMed1996

Epidemiology & management of persistent diarrhoea in children of developing countries.

Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised estimates in developing countries including India showed that acute diarrhoea accounts for 35 per cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for 45 per cent of total diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that increase the risk of acute diarrhoea becoming persistent have been identified in India and other developing countries. These include antecedent malnutrition, micronutrient deficiency particularly for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk. Several issues regarding the management of persistent diarrhoea in hospitalized children in India have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated. In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose hasten recovery. The role of antimicrobial agents and individual micronutrients in PD is currently being investigated. A management algorithm appropriate for India and other developing countries has been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed.

Animals↗