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Biomedical subjects

R Choudhury

Publications and source records attributed to R Choudhury.

18 recordsLinked to original sources
PubMed2004

Atomic force algorithms in density functional theory electronic-structure techniques based on local orbitals.

Electronic structure methods based on density-functional theory, pseudopotentials, and local-orbital basis sets offer a hierarchy of techniques for modeling complex condensed-matter systems with a wide range of precisions and computational speeds. We analyze the relationships between the algorithms for atomic forces in this hierarchy of techniques, going from empirical tight-binding through ab initio tight-binding to full ab initio. The analysis gives a unified overview of the force algorithms as applied within techniques based either on diagonalization or on linear-scaling approaches. The use of these force algorithms is illustrated by practical calculations with the CONQUEST code, in which different techniques in the hierarchy are applied in a concerted manner.

Journal Article↗
PubMed2001

Mutational analysis of zinc resistance in Pseudomonas putida strain S4.

The genes for resistance to any essential metal ion are generally tightly regulated. In Pseudomonas putida strain S4, a multiple metal-resistant strain, mutational analysis gave strong evidence to the presence of the same for the expression of Zn resistance. Zn-sensitive mutants showed a lower MTC of Zn and expressed the Zn resistance genes with a lower efficacy. Non-complementation between these mutants suggests that they are possibly involved in the same function. Altered response to Zn of these mutants assisted in predicting the involvement of a repressor protein regulating the expression of Zn resistance genes. Zn hypersensitive mutant, on the other hand, appears to have an unregulated Zn uptake. This seems to provide the sensor component in the regulation. Zn resistance in strain S4 consists of three steps, viz., uptake, efflux, and binding, which are shared by a Zn homeostasis mechanism as well.

Bacterial Proteins↗
PubMed1999

Interactions of the flavonoid naringenin in the gastrointestinal tract and the influence of glycosylation.

We have studied interactions in the gastrointestinal tract of flavonoids and the influence of glycosylation on their subsequent metabolism by examining the urinary recoveries of the flavonoid naringenin-7-glucoside and its aglycone, in the conscious rat model, after oral and intravenous administration. Absorption studies were also conducted using an in vitro isolated rat jejunum. The results show that ca. 10% of the administered dose of naringenin was recovered after oral dosing, the majority as naringenin glucuronide, whereas, after intravenous administration, the recovery of the glucuronide was ca. 20%. In contrast, after oral dosing of naringenin-7-glucoside, its hydrolysis product naringenin (0.5%) and naringenin glucuronide (12.7%) were detected. After intravenous dosing the majority of that identified in the urine was as the native glucoside. These findings suggest that, via the oral route, the glycoside group is cleaved by an intestinal enzyme prior to glucuronidation within the epithelium. This is substantiated by the urinary elimination of the native glucoside and the lack of detection of glucuronide after intravenous administration. Transport studies with isolated intestine showed that neither unchanged naringenin nor the 7-glucoside was absorbed in significant quantities across the gut wall. The major metabolite detected in both cases was naringenin glucuronide, thus supporting the notion that glucuronidation as well as hydrolysis can occur at the intestinal epithelium.

Administration, Oral↗
PubMed1999

The small intestine can both absorb and glucuronidate luminal flavonoids.

We have studied the perfusion of the jejunum and ileum in an isolated rat intestine model with flavonoids and hydroxycinnamates and the influence of glycosylation on the subsequent metabolism. Flavone and flavonol glucosides and their corresponding aglycones are glucuronidated during transfer across the rat jejunum and ileum and this glucuronidation occurs without the need for gut microflora. Furthermore, this suggests the presence of glycosidases as well as UDP-glucuronyl transferase in the jejunum. In contrast, quercetin-3-glucoside and rutin are mainly absorbed unmetabolised. The results suggest that the more highly reducing phenolics are absorbed predominantly as glucuronides (96.5%+/-4.6) of the amount absorbed, whereas monophenolic hydroxycinnamates and monophenolic B-ring flavonoids are less predisposed to glucuronidation and higher levels of aglycone (88.1%+/-10.1) are detected on absorption through both the jejunum and ileum.

Animals↗
PubMed1999

Urinary excretion of hydroxycinnamates and flavonoids after oral and intravenous administration.

The urinary recoveries of the hydroxycinnamates, ferulic acid (3-methoxy, 4-hydroxy cinnamic acid), and chlorogenic acid (the quinic acid ester of 3,4-dihydroxycinnamic acid), and three structurally related flavonoids were studied in the rat. For the latter, the aglycone quercetin was compared with its 3-glucoside (isoquercitrin) and 3-rhamnoglucoside (rutin). Doses of 50 mg/kg were administered via the oral and intravenous routes and urine collected over the subsequent 24-h period. Reverse phase HPLC with photo-diode array detection was used to analyze the unchanged compound and their metabolites excreted in the urine. Ferulic acid and isoquercitrin were orally absorbed (5.4 and 0.48% of administered dose, respectively) and are therefore bioavailable. In contrast, neither unchanged chlorogenic acid, rutin, quercetin, nor the conjugated metabolites in the form of glucuronide or sulphate were detected in the urine after oral dosing. All the flavonoids studied produced low total urinary recoveries after intravenous administration, 9.2% for quercetin-3-rhamnoglucoside, 6.7% for the 3-glucoside, and 2.4% for the aglycone, indicating that extensive metabolism to low molecular weight compounds or excretion via other routes may be occurring. Overall it can be stated that renal excretion is not a major pathway of elimination for intact flavonoids and hydroxycinnamates in the rat.

Administration, Oral↗
PubMed1999

Hematopoietic retroviral gene marking in patients with follicular non-Hodgkin's lymphoma.

We conducted a double retroviral vector (RV) gene marking trial to test for the possible contribution to relapse of follicular non-Hodgkin's lymphoma (FNHL) cells present in bone marrow (BM) and peripheral blood (PB) grafts used for hematopoietic reconstitution of patients undergoing myelaoblative chemotherapy and autologous transplant. CD34 positive selection using the CellPro Ceprate CD34 column was performed on PB mononuclear cells obtained after cyclophosphamide/G-CSF mobilization. CD34 positive cells were exposed for 4-6 hours to the LNL6 or G1 Na RV in the absence of growth factors or stromal monolayers. One week later, BM mononuclear cells were similarly processed. Patients then received total body irradiation (TBI), cyclophosphamide, and etoposide followed by infusion of both PB and BM CD34 positive cells. Semiquantitative Southern blot analysis of DNA t(14;18) amplification products showed approximately a three log reduction in t(14;18) positive cells after CD34 positive selection. The first patient showed evidence of engraftment with RV positive BM and PB cells for 9 months. He relapsed one year after transplant. At relapse, one year after transplant, he had lost evidence of RV positive cells in ficolled mononuclear BM and PB cells as well as in CD19 positive cells. The second and third patients showed evidence of engraftment with RV positive cells up to 9 and 6 months post BMT respectively. The second and third patients are still in clinical remission. Our results demonstrate engraftment of RV transduced hematopoietic cells in the PB and BM for up to 9 months.

Adult↗
PubMed1997

Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat.

Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl]-2-ethyl-3-hydroxypyridin-4-one (CP117) were studied in the rat. Urinary recovery studies were conducted in normal (oral and intravenous) and iron-overloaded rats (500 mg Fe/kg body weight; oral only). In normal rats, the majority of the dose recovered in the urine was as the hydrophilic metabolite, CP102, accounting for 69.7 +/- 9.4% (oral) and 80.7 +/- 7.9% (intravenous) of the administered dose. There was, however, a dramatic decrease in the amount of CP102 recovered (47.7 +/- 5.9%) (p < or = 0.05) in the iron-loaded group of animals. The amount of CP102 glucuronide conjugate recovered in the normal and iron-overloaded rats after oral administration of CP117 did not differ significantly with values of 6.5 +/- 2.5% and 7.1 +/- 2.5%, respectively. There was, however, a significant increase in CP102 glucuronide conjugate (13.7 +/- 3.0%) (p < or = 0.05) after intravenous administration of CP117. Urinary iron content was determined in the iron-overloaded and normal (oral) animals. Negligible levels of the CP117 iron complex and only 0.6 +/- 0.2% was present as the corresponding CP102 complex in the urine of normal animals. Less than 0.1% of the administered dose was recovered as CP117-iron complex and only 1.3 +/- 0.2% as CP102-iron complex in the iron-overloaded animals. Total recovery of the administered dose was significantly different between normal (po) and iron-overloaded groups of animals, decreasing from 76.4 +/- 11.7% to 57.2 +/- 9.6%, respectively (p < or = 0.05). There was no significant difference between the two routes of administration in normal animals, with total recovery of the administered dose of CP117 being 96.1 +/- 9.1% by the intravenous route. Intravenous and oral pharmacokinetics of CP117 was studied in the rat at a fixed dose of 450 mumol/kg. The AUC of the drug was 43.2 +/- 9.1 mumol/liter . hr and 4.1 +/- 1.8 mumol/liter.hr via the intravenous and oral routes, respectively, thus indicating that the systemic bioavailability of the drug is < 10%. Pharmacokinetic parameters of the drug determined by the intravenous route indicate that CP117 has a plasma clearance of 10.9 +/- 3.0 mumol/liter.hr, a mean residence time of 0.14 +/- 0.05 hr, and volume of distribution at steady-state of 1.54 +/- 0.52 liters.kg-1. The Cmax and tmax of CP117 were 12.1 +/- 2.5 mumol/liter and 7.0 +/- 2.7 min, respectively. The AUC of the main metabolite, CP102, decreased from 425.3 +/- 8.5 mumol/liter.hr to 282 +/- 31 mumol/liter.hr via the intravenous and oral routes, which is presumed to reflect differences in hepatic extraction and routes of elimination of the drug. Parallel absorption studies conducted using the in situ isolated rat gut loop model indicate that the majority of the administered dose was absorbed intact as the parent drug with mesenteric vein AUC values of 3.1 +/- 1.7 mmol/liter.hr and 0.3 +/- 0.04 mmol/liter.hr for CP117 and CP102, respectively.

Animals↗
PubMed1996

Design of orally active iron chelators.

Three parameters which are critical for the development of non-toxic orally active iron chelators are identified: bioavailability, selectivity for iron (III) and distribution and toxicity. Each is discussed in detail. Arguments are presented for the use of bi- and tridentate ligands as opposed to hexadentate ligands. The discussion leads to the identification of 3-hydroxpyridin-4-ones as compounds with a unique potential for iron chelation under clinical conditions. The prodrug concept utilising efficient liver first-pass kinetics is introduced.

Administration, Oral↗
PubMed1995

Serum levels of six pancreatic enzymes as related to the degree of renal dysfunction.

OBJECTIVES: Currently, serum total amylase, pancreatic isoamylase (P-amylase), lipase, trypsin(ogen), phospholipase A2 (PLA2), and elastase I are advocated to be useful in diagnosing pancreatic diseases. However, the most useful among the above six enzymes in patients with impaired renal function has not been fully clarified. We, therefore, studied the relation of the serum levels of the above enzymes and creatinine clearance (CrCl) in normal controls and patients with chronic renal insufficiency or failure. METHODS: PLA2 and elastase I were assayed by RIA, trypsin(ogen) by EIA and others by activity. Subjects were 24 healthy controls and 47 patients with impaired renal function and no apparent pancreatic diseases. RESULTS: 1) Elastase I was significantly elevated only in patients with a CrCl of 10 ml/min or less, whereas others were elevated already in patients with a CrCl below 40 ml/min; 2) in 12 patients with a CrCl between 13 and 39 ml/min, lipase tended to be less frequently raised than others, except elastase I, although the difference was statistically insignificant; 3) in 28 patients with a CrCl between 40 and 74 ml/min, lipase was less frequently elevated than others, except elastase I and PLA2; 4) in seven patients with a CrCl of 10 ml/min or below, elastase I tended to be less frequently elevated than others, although the difference was statistically insignificant; and 5) the degree of elevation was within 2.5 times the upper limits of reference values in all enzymes, except trypsin(ogen) (within 4.8 times). CONCLUSIONS: Elastase I was least vulnerable to impaired renal function followed by lipase. We, therefore, recommend combined assays of elastase I and lipase for detecting pancreatic diseases in patients with renal insufficiency. When cut-off levels are set at 2.5 times the upper limit of reference values, P-amylase or PLA2 can replace lipase.

Aged↗
PubMed1995

Effect of iron overload on the metabolism and urinary recovery of 3-hydroxypyridin-4-one chelating agents in the rat.

Three orally active iron chelating agents from the 3-hydroxypyridin-4-one series of compounds were administered by gavage to both normal and iron-overloaded (500 mg Fe/kg) rats at a dose of 450 mumol/kg to investigate the effect of iron loading on metabolism and urinary recovery. Compounds selected for investigation were either poorly metabolized [1-(2'-hydroxyethyl) derivative, CP102] or predominantly biotransformed by either phase I [1,2-diethyl derivative, CP94] or phase II (1,2-dimethyl derivative, CP20) metabolic pathways. Unchanged drug and metabolite(s) recovered in urine were determined by HPLC and iron levels by atomic absorption spectrometry. Significant differences in recovery of unchanged drug were seen for both CP20 (L1) and CP94 between normal and iron-overloaded animals. In contrast, no such difference was seen for the poorly metabolized compound, CP102. For CP20 (L1), the proportion of unchanged drug excreted in the urine increased from 36.2 +/- 9.9% in normal animals to 78.7 +/- 8.1% (p < or = 0.02) in iron-loaded animals and 20.1 +/- 4.5% to 39.9 +/- 8.6% for CP94 (p < or = 0.05). A significant decrease in metabolite recovery of CP20 (L1) was seen with the 3-O-glucuronide conjugate decreasing from 38.2 +/- 8.8% in normal animals to 2.5 +/- 2.0% in the iron-overloaded group. The decrease of the 2-(1'-hydroxyethyl) metabolite of CP94 from 41.4 +/- 6.6% to 29.4 +/- 4.6% in the iron-loaded animals was, however, not statistically significant. Total dose recovered in the urine between normal and iron-overloaded animals was only significant for CP94 (p < or = 0.05).

Animals↗
PubMed1992

Active infective endocarditis observed in an Indian hospital 1981-1991.

Clinical data from 186 patients (133 males and 53 females) with 190 episodes of infective endocarditis (IE) occurring between January 1981 and July 1991 were studied retrospectively at a large referral hospital in Northern India with the intention of highlighting certain essential differences from those reported in the West. The mean age was much lower (25 +/- SD 12 years, range 2 to 75 years). Rheumatic heart disease was the most frequent underlying heart lesion accounting for 79 patients (42%). This was followed by congenital heart disease in 62 (33%) and normal valve endocarditis in 17 (9%). Twenty-four patients had either aortic regurgitation (n = 15) or mitral regurgitation (n = 9) of uncertain etiology. Prosthetic valve infection and mitral valve prolapse were present in only 2 patients each. A definite predisposing factor could be identified in only 28 patients (15%). Postabortal sepsis and sepsis related to childbirth accounted for 6 and 5 cases, respectively. Only 1 patient had history of intravenous drug abuse. Two-dimensional echocardiography showed vegetations in 121 patients (64%). Blood cultures were positive in only 87 (47%), with a total of 90 microbial isolates. Commonest infecting organisms were staphylococci (37 cases) and streptococci (34 cases). Except for a significantly higher number of patients with neurologic complications in the culture-negative group, there were no differences between patients with culture-positive and culture-negative IE. Of the 190 episodes of IE, the patients had received antibiotics before admission in 110 (58%) instances. A significantly greater number of culture-negative patients had received antibiotics than did culture-positive patients (87 vs 23, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Profile of right-sided endocarditis: an Indian experience.

The clinical profile of right-sided infective endocarditis in India was studied from a review of records of patients with infective endocarditis admitted to this hospital. From November 1982 to November 1989, 109 patients with infective endocarditis showed vegetations on cross-sectional echocardiography confirming the diagnosis of infective endocarditis. In 19 (17.4%) patients, only the right side of the heart was involved: specifically the tricuspid valve alone in 10; tricuspid and pulmonary valves in 4; tricuspid valve and right ventricular outflow tract in 1; tricuspid valve and right ventricular free wall in 1; pulmonary valve alone in 2; and bifurcation of pulmonary trunk in 1. Eleven patients (57.9%) had underlying congenital heart disease whereas the remaining 8 patients (42.1%) did not have any underlying heart disease. The latter group, therefore, had isolated right-sided infective endocarditis. Previous illnesses leading to isolated right-sided infective endocarditis were: puerperal sepsis in 4; septic abortion in 1; staphylococcal pneumonia in 2; and epididymoorchitis in one. Eight out of 11 patients with congenital heart disease did not report any previous illness. In the remaining 3, right-sided endocarditis followed cardiac surgery in one; dental extraction without prophylaxis in one; and pulmonary balloon valvoplasty in one. All patients with isolated right-sided infective endocarditis had features of septicaemia, but a murmur of tricuspid regurgitation was audible in only 4 (50%) of them. We conclude that, unlike western reports, the pattern of right-sided infective endocarditis in India is different. No drug addict with right-sided infective endocarditis was seen; puerperal sepsis and septic abortion were the commonest causes of isolated right-sided infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Septic↗
PubMedDate not supplied

Metabolism and pharmacokinetics of 1-(2'-hydroxy-ethyl)- and 1-(3'-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-ones in the rat.

The urinary recovery (p.o.) and pharmacokinetics (i.v. and p.o.) of two compounds from the 1-hydroxyalkyl-3-hydroxypyridin-4-one series. 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridine-4-one (CP102) and 1-(3'-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-one (CP106) were studied in the rat. The pharmacokinetics of the 1-carboxyethyl metabolite (CP110) of CP106 was also studied (i.v.). CP102 was not metabolised to any considerable extent with 68.4 +/- 12.2% of the administered dose recovered unchanged in rat urine. In contrast, CP106 undergoes extensive phase I metabolism to form the 1-carboxyalkyl metabolite which accounted for 56.4 +/- 11% of the administered dose with 22.0 +/- 1.0% as unchanged drug. Intravenous and oral pharmacokinetics of CP102 and CP106 were studied in the rat at 450 mumols/kg. The AUCs of CP102 and CP106 after bolus i.v. infusion were 458 +/- 38 and 171 +/- 20 mumols/l.h. The AUC values after bolus oral administration were 318 +/- 46 and 77 +/- 18 mumols/l.h, respectively, with corresponding bioavailabilities (F) of 0.69 and 0.45. The Cmax of CP102 and CP106 were 142 +/- 25 and 70 +/- 15 mumols/l with Tmax values of 0.75 +/- 0.15 and 0.50 +/- 0.10 h, respectively. The CL, MRT and Vdss of CP102 was 1.00 +/- 0.09 l/kg/h, 0.92 +/- 0.04 h and 0.91 +/- 0.05 l/kg, respectively. The corresponding pharmacokinetic parameters for CP106 were 2.64 +/- 0.20 l/kg/h, 0.42 +/- 0.12 h and 1.12 +/- 0.26 l/kg, respectively. Renal clearance (CLR) of CP102 and CP106 were 1.00 +/- 0.18 l/kg and 1.27 +/- 0.31 l/kg respectively. The pharmacokinetics of CP110, which was conducted by the i.v. route only at a dose of 450 mumols/kg, had an AUC of 289 +/- 46 mumols/l.h, CL of 1.56 +/- 0.29 l/kg/h, MRT of 0.25 +/- 0.09 h and Vdss of 0.40 +/- 0.13 l/kg, respectively.

Animals↗
PubMedDate not supplied

Clonidine suppression test--an evaluation of its diagnostic significance in hypertensive patients.

The Clonidine Suppression Test (CST) was performed in 8 patients with Labile hypertension (Group I), 8 patients with mild and moderate Essential hypertension (Group IIa), 8 patients with severe Essential hypertension (Group IIb) and 6 patients with pheochromocytoma (Group III). The mean plasma catecholamine (CA) levels as estimated by a Spectrofluorimetric method were significantly reduced 3-4 hours after administration of clonidine (5 micrograms/kg) by mouth in Group I, IIa & IIb patients. Plasma norepinephrine levels fell from 1.82 +/- SEM 0.35 ng/ml to 1.03 +/- 0.11 ng/ml (p less than 0.05) in Group I, 1.64 +/- 0.36 ng/ml to 0.88 +/- 0.12 ng/ml (p less than 0.025) in Group IIa, 1.23 +/- 0.16 ng/ml to 0.86 +/- 0.12 ng/ml (p less than 0.005) in Group IIb patients. Plasma epinephrine levels fell from 0.35 +/- 0.06 ng/ml to 0.16 +/- 0.03 ng/ml (p less than 0.05) in Group I, 0.34 +/- 0.04 ng/ml to 0.22 +/- 0.03 ng/ml (p less than 0.01) in Group IIa, 0.33 +/- 0.06 ng/ml to 0.18 +/- 0.03 ng/ml (p less than 0.025) in Group IIb patients. The blood pressure and heart rate showed a similar response. By contrast, in patients with pheochromocytoma, the mean plasma CA levels did not show any significant fall, and even rose during the CST, but, when repeated post-operatively, showed normal suppression. No serious side effects were noticed. We conclude that the CST is a safe and reliable test for the diagnosis of pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗