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R K Gupta

Publications and source records attributed to R K Gupta.

At least 361 records · Page 20Linked to original sources
PubMed1993

Cellular ionic effects of insulin in normal human erythrocytes: a nuclear magnetic resonance study.

Elevated erythrocyte cytosolic free calcium, and suppressed free magnesium and pH values are associated with the hyperinsulinaemia and insulin resistance of hypertension, obesity, and Type 2 (non-insulin-dependent) diabetes mellitus. To determine the role of insulin in this process, we utilized 19F- and 31P-nuclear magnetic resonance spectroscopy to study the cellular ionic effects of insulin in vitro on normal human erythrocytes. Insulin elevated cytosolic free calcium levels in a dose- and time-dependent manner. The effect began at 10 microU/ml, peaked at 200 microU/ml, and continued at both the 500 microU/ml and 1000 microU/ml doses. At 200 microU/ml, free calcium levels rose from 24.6 +/- 2.5 nmol/l to a peak value at 120 min of 66.4 +/- 11 nmol/l (p < 0.05 vs basal), levels remaining elevated throughout the incubation (45.7 +/- 5.6 nmol/l at 60 min, and 47.9 +/- 9.1 nmol/l at 180 min, p < 0.05 vs basal, respectively). Similarly, insulin also increased intracellular free magnesium at all time points (basal: 177 +/- 11 mumol/l; 60 min: 209 +/- 19 mumol/l; 120 min: 206 +/- 22 mumol/l; and 180 min: 202 +/- 12 mumol/l; p < 0.05 vs basal at all times). No insulin-induced changes in pH were observed. We conclude: (i) that insulin in physiological concentrations may participate in regulating divalent cations in the mature human erythrocyte, (ii) that insulin per se cannot account for the previously described cellular ionic lesions of hypertension and diabetes, and (iii) that future clinical studies of cell ion metabolism should be conducted in the fasting state, be controlled for ambient circulating insulin levels, or both.

Calcium↗
PubMed1993

Intracellular and extracellular magnesium depletion in type 2 (non-insulin-dependent) diabetes mellitus.

To investigate alterations of magnesium metabolism in Type 2 (non-insulin-dependent) diabetes mellitus, we utilized a new magnesium-specific selective ion electrode apparatus to measure serum ionized magnesium (Mg-io) in fasting subjects with and without Type 2 diabetes, and compared these values to levels of serum total magnesium, and of intracellular free magnesium (Mgi) analysed by 31P-NMR spectroscopy. Both Mg-io (0.630 +/- 0.008 vs 0.552 +/- 0.008 mmol/l, p < 0.001) and Mgi (223.3 +/- 8.3 vs 184 +/- 13.7 mmol/l, p < 0.001), but not serum total magnesium, were significantly reduced in Type 2 diabetes compared with non-diabetic control subjects. Furthermore, a close relationship was observed between serum Mg-io and Mgi (r = 0.728, p < 0.001). We suggest that magnesium deficiency, both extracellular and intracellular, is a characteristic of chronic stable mild Type 2 diabetes, and as such, may predispose to the excess cardiovascular morbidity of the diabetic state. Furthermore, by more adequately reflecting cellular magnesium metabolism than total serum magnesium levels, Mg-io measurements may provide a more readily available tool than has heretofore been available to analyse magnesium metabolism in a variety of diseases.

Blood Glucose↗
PubMed1993

Problems with the "dural tail" sign.

Prominent enhancement of the dura mater, the "dural tail" adjacent to a peripherally located mass on gadolinium-enhanced MRI has been described as being characteristic of meningiomas. We present a cerebral glioma showing the classical "dural tail".

Brain↗
PubMed1993

Experimental candidiasis in Japanese quail: pathological changes.

Candidiasis was experimentally produced in young Japanese quail by oral administration of Candida albicans cells. Lesions were confined to upper digestive tract with most characteristic changes occurring on the mucosa of crop. No lesions were observed in other tissues of the body. The initial changes in the crop were characterized by thickening and yellowish-white necrotic plaques on the mucosa. From 10th day onwards, there was marked thickening and corrugations of the crop mucosa giving it a typical 'turkish towel' appearance. Varying degree of mucosal swelling was also observed in the oesophagus and proventriculus. Two of the infected birds also revealed yellowish-white necrotic plaques on the tongue at 7th and 10th day post-infection. The prominent microscopic lesions in the crop and tongue consisted of hyperkeratosis and parakeratosis with congestion of the subepithelial tissues. Varying degree of parakeratosis and epithelial hyperplasia coupled with subepithelial oedema and hypertrophy of glands was observed in the oesophagus. The proventriculus and small intestine revealed congestion, oedema, mild to marked goblet cell hyperplasia and focal epithelial sloughing. Fungal elements could be demonstrated in the sections of tongue up to 10 days while in crop up to 14 days post-infection. Reisolation of the fungus was consistently achieved from the crop of infected birds throughout the duration of the experiment.

Animals↗
PubMed1993

Multiple pituitary hormone deficiencies in a patient with spinocerebellar ataxia: magnetic resonance imaging and hormonal studies.

Degenerative spinocerebellar ataxia has a rare association with hypogonadotropic hypogonadism. In this report we present the results of the detailed endocrine evaluation and magnetic resonance imaging in one such patient. A 20-year-old male with progressive cerebellar ataxia, hypogonadism, and short stature was investigated. Basal testing revealed hypogonadotropic hypogonadism (LH < 5 mU/L, FSH < 5 mU/L, testosterone 2.5 nM/L). There was no rise in LH after stimulation with LHRH, peak LH level being < 5 mU/L. Insulin hypoglycemia testing was consistent with GH deficiency, with peak GH being 3.2 mU/L. On TRH stimulation, there was no significant rise in prolactin, though the TSH response was normal. Magnetic resonance imaging revealed cerebellar atrophy. The anterior pituitary was atrophic, with a height of 1.4 mm. The posterior pituitary and the pituitary stalk were normal in size and position. This patient with degenerative spinocerebellar ataxia had multiple pituitary hormone deficiencies. The results of our endocrine evaluation and MR imaging lead us to believe that these deficits may result from a lesion at the level of the pituitary gland.

Adult↗
PubMed1993

Adjuvants--a balance between toxicity and adjuvanticity.

Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions. The most common adjuvants for human use today are still aluminium hydroxide, aluminium phosphate and calcium phosphate although oil emulsions, products from bacteria and their synthetic derivatives as well as liposomes have also been tested or used in humans. In recent years monophosphoryl lipid A, ISCOMs with Quil-A and Syntex adjuvant formulation (SAF) containing the threonyl derivative of muramyl dipeptide have been under consideration for use as adjuvants in humans. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side effects.

Adjuvants, Immunologic↗
PubMed1993

Intracranial tuberculomas: MRI signal intensity correlation with histopathology and localised proton spectroscopy.

In seven cases of intracranial tuberculomas showing different signal intensities on MRI (five characteristic and two nonspecific), detailed histopathological examination was performed to look for number of macrophages, fibrosis, gliosis, degree of inflammatory cellular infiltrate, and type of caseation. The granulomas showing more macrophages, fibrosis and gliosis appeared hypointense on T2-weighted images. Tuberculomas showing minimal macrophages, marked cellular infiltration, and minimal fibrosis appeared hyperintense on T2-weighted images. Lesions showing similar signal intensity on T2-weighted images showed variation in the amount of macrophages, cellular infiltrates, maturity and fibrosis. Trace element estimation was done (iron, copper, and magnesium) in two of these lesions appearing hypointense on T2 and two normal brain samples; these were significantly lower in tuberculoma compared to normal brain tissue. Localised proton spectroscopy was performed in two hypointense lesions which showed marked increase in peaks in the region of mobile lipids (1.28 ppm) compared to normal brain parenchyma. It is concluded that the signal intensity of the lesions is dependent on the number of macrophages, fibrosis and cellular infiltrates. In addition increased lipid contents in the tuberculoma also contribute to the hypointensity on T2-weighted images.

Adult↗
PubMed1993

19F nuclear magnetic resonance studies of free calcium in heart cells.

19F nuclear magnetic resonance is used in conjunction with 5,5'-difluoro-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBapta), a fluorinated calcium chelator, to report steady-state intracellular free calcium levels ([Ca2+]i) in populations of resting, quiescent, isolated adult heart cells. 31P nuclear magnetic resonance shows that 5FBapta-loaded cells maintain normal intracellular high-energy phosphates, pH, and free Mg2+. The intracellular free calcium concentration of well perfused, isolated heart cells is 61 +/- 5 nM, measured with 5FBapta, which has a dissociation constant (Kd) for calcium chelation of 500 nM. A similar value is obtained with Quin-MF, another fluorinated calcium chelator with Kd and maximum calcium sensitivity at 80 nM. We find that the steady-state level of intracellular free calcium is increased by decreased extra-cellular sodium concentration, omission of extracellular magnesium, decreased extracellular pH, hyperglycemia, and upon treatment with lead acetate. Further, extracellular ATP caused a large transient increase in [Ca2+]i. Thus, while heart cells maintain a very low level of intracellular free Ca2+, acute alterations in extracellular environment can cause derangement of calcium homeostasis, resulting in measurable increases in [Ca2+]i.

Adenosine Triphosphate↗
PubMed1993

Signal intensity patterns in intraspinal dermoids and epidermoids on MR imaging.

Retrospective evaluation of MR images of nine intraspinal dermoid (n = 4) and epidermoid (n = 5) tumours was undertaken. T1-weighted images were available in all the patients while proton density (PD) and T2-weighted images were available in seven patients. Except for one lesion (only T1-weighted images were available in this case), all the lesions were clearly delineated on MR images. Most (5 out of 7) were better appreciated on T1- and PD-weighted images than on T2-weighted images. On T1-weighted images, the epidermoids were either iso- to mildly hypointense to the cord (n = 3), isointense to CSF (n = 1) or markedly hyperintense (n = 1). On the PD images, the epidermoids were either isointense to cord (n = 3) or markedly hyperintense (n = 1). All the lesions were iso- to hyperintense to CSF on T2-weighted images. Of the four dermoids three showed a mixed intensity pattern on all sequences; the dominant component gave short T1 and short T2 values, consistent with fat. The fourth lesion showed homogenous material with a signal intensity intermediate between that of CSF and cord on T1-weighted images. Dermal sinus tracts were present in four of the nine patients; three patients had an intraspinal component. This study shows that although MR imaging is excellent for their detection, it cannot differentiate the two tumour types.

Cerebrospinal Fluid↗
PubMed1993

Determinants of release rate of tetanus vaccine from polyester microspheres.

Controlled-release formulations based on poly(lactic) (PLA) and poly(lactic/glycolic) acid (PLGA) microspheres containing tetanus vaccine were designed. The polymers forming the microspheres were L-PLA of different molecular weights and DL-PLGA, 50:50. These microspheres were prepared by two solvent elimination procedures, both using a double emulsion, and were characterized for size, morphology, and toxoid release kinetics. The influence of formulation variables such as polymer type, vaccine composition, and vaccine/polymer ratio was also investigated. Both techniques yielded microspheres with similar size, morphology, and release properties. Microsphere size was dependent on the type of polymer and the presence of the surfactant L-alpha-phosphatidylcholine, which led to a reduction in microsphere size. On the other hand, the release kinetics of encapsulated protein were affected by the polymer properties (ratio lactic/glycolic acid and molecular weight) as well as by the vaccine composition, vaccine loading, and microsphere size. Moreover, for some formulations, a decrease in microsphere size occurred simultaneously, with an increase in porosity leading to an augmentation of release rate. The changes in the PLA molecular weight during in vitro release studies indicated that release profiles of tetanus toxoid from these microspheres were only marginally influenced by polymer degradation. A significant fraction of protein (between 15 and 35%) was initially released by diffusion through water-filled channels. In contrast, the decrease in the PLGA molecular weight over the first 10 days of incubation suggested that erosion of the polymer matrix substantially affects protein release from these microspheres. Among all formulations developed, two differing in microsphere size, polymer hydrophobicity, and release profile were selected for in vivo administration to mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Independent effects of hyperinsulinemia and hyperglycemia on intracellular sodium in normal human red cells.

To study the contribution of glucose vis-à-vis insulin in the altered sodium homeostasis of diabetes mellitus, we utilized 23Na-NMR spectroscopy to noninvasively measure intracellular sodium (Nai) in red blood cells of non-diabetic, thin, normotensive subjects (n = 9), before and 60, 120, and 180 min after in vitro incubation with elevated glucose (15 mmol/L) and insulin (200 mumol/L) concentrations. Hyperglycemia caused a significant rise in Nai compared to basal values at 60 (9.1 +/- 0.8 to 9.7 +/- 0.8 mEq/L, P < .05), and 120 min (10.0 +/- 0.7 mEq/L, P < .05 v basal). Hyperinsulinemia induced a more pronounced and prolonged elevation of Nai. Significant elevations occurred at 60 (8.0 +/- 0.5 to 10.2 +/- 0.7 mEq/L, P < .05), 120 (10.5 +/- 1.1) mEq/L, P < .05 v basal), and 180 (9.1 +/- 0.5 mEq/L, P < .05 v basal) minutes. Thus, both hyperinsulinemia, and to a lesser extent, hyperglycemia cause intracellular sodium accumulation in normal human red cells. Since glucose transport in red cells is not insulin-dependent, insulin and glucose presumably exert their effects independently. Altogether, we suggest that these insulin- and glucose-mediated effects on cellular sodium, if present in other tissues as well, may underlie the increased total body sodium and the salt-dependent hypertension characteristic of chronic diabetic or hyperinsulinemic syndromes.

Erythrocytes↗
PubMed1993

Ionic basis of hypertension in diabetes mellitus. Role of hyperglycemia.

Alterations of cell ion content have been reported acutely after oral glucose ingestion, and chronically in subjects with hypertension and noninsulin dependent diabetes mellitus (NIDDM). We have hypothesized that these ionic abnormalities, elevated cytosolic free calcium (Cai), and suppressed intracellular pH (pHi) and free magnesium (Mgi), common to both of these syndromes, may explain their frequent clinical coincidence. To investigate the potential role of glucose in this process, we utilized 19F- and 31P-NMR spectroscopy to measure Cai, Mgi, and pHi in normal human red blood cells before and 60, 120, and 180 min after in vitro incubation with glucose (15 mmol/L) and equimolar concentrations of the glucose analogs, L-glucose, 2-deoxyglucose, and 3-O-methylglucose. At each point in time (from t = 0 to t = 60, 120, 180 min), glucose induced significant (P < .05) elevations in Cai (27.2 +/- 2.2 to 68.3 +/- 7.2, 70.7 +/- 10.5, 59.8 +/- 10.1 nmol/L), while suppressing pHi (7.28 +/- 0.02 to 7.22 +/- 0.03, 7.23 +/- 0.03, 7.22 +/- 0.03), and Mgi (206 +/- 10 to 151 +/- 7, 131 +/- 7, 143 +/- 5 mumol/L). This glucose induced ionic effect was dose dependent, significant elevations in Cai being observed at 10 and 15 mmol/L, but not at the other concentrations tested. It was also specific, no changes in Cai being observed with any of the glucose analogs tested. Thus, hyperglycemia per se elevates Cai and suppresses Mgi and pHi in normal human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Relationship between antidepressant response and plasma concentrations of fluoxetine and norfluoxetine.

The relationship between plasma concentration, clinical outcome and side-effects was examined in 23 patients with major depressive disorder (DSM-III-R) treated with fluoxetine. All patients received a fixed dose of 20 mg for 6 weeks. Good response was observed in 57% of patients, while 30% of patients had moderate responses after 6 weeks of treatment. Fluoxetine and norfluoxetine plasma concentrations were not significantly influenced by age and sex. At 6 weeks, plasma fluoxetine concentrations were not significantly different between responders and non-responders to treatment (82.2 +/- 59.6 micrograms/l vs. 84.7 +/- 6.7 micrograms/l) or those with or without side-effects (74.6 +/- 28.7 micrograms/l vs. 87.0 +/- 66.6 micrograms/l). Similarly, norfluoxetine concentrations were not significantly different for responders and non-responders (65.5 +/- 28.9 micrograms/l vs. 66.5 +/- 26.2 micrograms/l) or those with or without side-effects (66.6 +/- 14.4 micrograms/l vs. 61.5 +/- 33.6 micrograms/l). Plasma concentrations and clinical outcome were not related in a simple manner. Further studies are needed to evaluate the role of monitoring plasma fluoxetine/norfluoxetine concentrations as a routine procedure.

Adult↗
PubMed1993

A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness.

The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.

Adult↗
PubMed1993

Diagnosis of metastatic carcinoma of stomach using fine catheter aspiration cytology.

The value of fine catheter aspiration cytology organs of the peritoneal cavity in the diagnosis of a metastatic carcinoma is illustrated by this case report. The finding of unequivocal malignant cells was quite unexpected and led to an investigation of the gastrointestinal tract which demonstrated a primary carcinoma in the stomach. This was further confirmed on a biopsy of the tumor and cell block preparations of aspirated material on which immunostaining was done and which further substantiated the light microscopic cytohistologic diagnosis. The findings presented in this article further emphasize the value of fine catheter aspiration cytology in not only identifying tumor type or predicting the source of the primary but also in managing patients admitted with abdominal pain as an emergency who may be saved from an unnecessary laparotomy which would have otherwise been done for a diagnosis.

Aged↗
PubMed1993

Aspiration cytodiagnosis of mucinous cystadenocarcinoma of the pancreas.

A case of mucinous cystadenocarcinoma of the pancreas is described in which the cytodiagnosis was made from aspirated material which was obtained under computed tomography (CT) guidance. The case presented further supports the view that aspiration cytodiagnosis of mucinous cystadenocarcinoma (an uncommon pancreatic tumor) can be made with confidence when performed with imaging assistance.

Aged↗