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Biomedical subjects

S K Basu

Publications and source records attributed to S K Basu.

At least 73 records · Page 4Linked to original sources

Studies on the intravenous pharmacokinetics in rabbit and in vitro protein binding of two new salts of erythromycin: erythromycin maltobionate and erythromycin fumarate.

Pharmacokinetics in rabbits following intravenous administration and in vitro protein binding were studied for two new salts of erythromycin (erythromycin maltobionate and erythromycin fumarate). Serum erythromycin levels following intravenous injection were described by two compartment model kinetics, and values for the distribution volume of the central compartment, the peripheral compartment and overall distribution volume were calculated. The elimination half-lives of erythromycins in serum were 83 min, 168 min, and 103 min for erythromycin maltobionate, erythromycin fumarate, and erythromycin lactobionate (reference standard), respectively. The erythromycin salts were highly (c. 90 per cent) protein bound, but the binding was found to be reversible. Differences in the pharmacokinetic parameters after administration of equivalent doses of the salts, indicate possible variation in efficacies of different salts.

Animals↗

C-peptide response to oral glucose and its clinical role in elderly people.

C-Peptide response to oral glucose was measured in 45 elderly diabetics, in whom final treatment was established on clinical grounds during a 16-18 months follow-up. The diabetic patients comprised 19 ultimately classified as insulin-dependent (IDD) (group 1) and 26 regarded as non-insulin-dependent (NIDD) (group 2). Fifteen matched controls (group 3) and 15 young controls (group 4) were similarly studied. Fasting C-peptide values were lower in groups 1 and 2 (1.48 +/- 0.39 and 2.14 +/- 0.22 ng/ml; mean +/- SEM, respectively) compared with groups 3 and 4 (2.51 +/- 0.16 and 2.71 +/- 0.20 ng/ml, respectively) (p less than 0.001). Peak C-peptide levels were reached at 30 min in healthy young and at 60 min in healthy elderly. All non-diabetic control subjects showed a peak of at least 6.5 ng/ml and an increment of at least 4 ng/ml. The ratio of C-peptide increment/blood glucose increment (100 delta CP/delta BG) at 60 min derived to assess beta-cell function was at least 90 in all healthy subjects. The ratio was less than 10 in 68% of IDD but in only 27% of NIDD patients (p less than 0.01). The 100 delta CP/delta BG was inversely related to the prevailing fasting blood glucose (FBG) (p less than 0.001). These findings suggest that C-peptide response to oral glucose may be a useful test in certain elderly diabetic patients whose insulin dependence is in question.

Aged↗

Radiation protection of male fertility in mouse and rat by a combination of 5-hydroxy-L-tryptophan and a thiol compound (AET).

Sperm abnormalities and fall in total sperm count following different doses (4 Gy, 5 Gy and 6 Gy) of whole body gamma irradiation (WBGR) were studied in adult male Swiss strain A mice. The protecting ability of a combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethyl isothiuronium bromide hydrobromide (AET, 20 mg/kg) was also investigated. Pretreatment with a 5-HTP+AET formulation i.p., 30 min before irradiation modified the fall in sperm counts significantly. Exposures to 4 Gy, 5 Gy and 6 Gy WBGR caused marked increase of sperm abnormalities which could be significantly reduced by pretreatment with 5-HTP-AET. WBGR with 4 Gy, 5 Gy and 6 Gy produced a short period of sterility associated with oligospermia but these abnormalities were corrected by pretreatment with 5-HTP+AET. This finding was supported by breeding experiments in pretreated adult male Sprague-Dawley rats which showed delivery of normal offsprings in drug-protected irradiated groups in contrast to irradiated controls.

5-Hydroxytryptophan↗

Present phage types and antibiotic susceptibility of salmonellae.

A total of 168 strains of Salmonella were isolated in the Command Pathology Laboratory (WC) Delhi Cantt during the year 1990. Out of this, 143 were Salmonella typhi, 17 Salmonella paratyphi A, 7 Salmonella typhimurium and 1 Salmonella manhattan. The commonest phage type and biotype of Salmonella typhi was type E1 and type 1 respectively. The dominant biotype of Salmonella paratyphi A was type I. There was a very high degree of multidrug resistance of most of the strains. But all the strains were sensitive to ciprofloxacin and norfloxacin.

Anti-Bacterial Agents↗

Protection to glycolysis by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats.

Rate of glycolysis in vivo at different time intervals following 8 Gy [LD100(30)] whole body gamma radiation (WBGR) was evaluated by estimating liver glycogen, blood sugar, serum lactic dehydrogenase (LDH) and blood lactic acid concentration in adult male Sprague Dawley rats. Within 1 hr of radiation exposure, a significant fall in liver glycogen was observed in rats fed food and water ad libitum. The glycogen content increased after 24 hr and had returned to control level on 7th day after radiation exposure. Blood sugar, serum LDH and blood lactate levels increased significantly as compared to non irradiated controls. Pretreatment with 5-hydroxy-L-tryptophan (5-HTP; 100 mg/kg) + 2-aminoethylisothiuronium bromide hydrobromide (AET; 20 mg/kg) ip 30 min before 8 Gy WBGR, modified these values and restored them to normal level on 7th day post-irradiation.

5-Hydroxytryptophan↗

Radioprotection of spleen by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats.

Radioprotective efficiency of the combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) with 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg) in protecting splenic tissue following 8 Gy whole-body gamma radiation (WBGR) has been studied in adult male Sprague Dawley rats. Loss in splenic weight, splenic cells and DNA was observed following & Gy WBGR, which was modified significantly in 5-HTP+AET (ip) pretreated group. The study further showed that pre-treatment with this formulation led to an increased superoxide dismutase (SOD) activity and a decrease in lactate/pyruvate ratio in the cytosol fraction of the spleen.

5-Hydroxytryptophan↗

Differential radioprotection of tissues in C3H/J mice by a combination of 5-hydroxy L-tryptophan with 2-aminoethylisothiuronium bromide hydrobromide.

Differential radioprotection between normal tissues and carcinoma was observed in C3H/J mice treated with a combination of 5-hydroxy L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg). Protection to normal tissues was judged by LD50(30) and by radiation induced damage to bone marrow(BM) using clonogenic ability of blood forming stem cells (10 day CFUs) as the criteria. Pretreatment with 5-HTP + AET combination 30 min before whole body gamma radiation (WBGR) enhanced the recoveries of the number of blood forming stem cells in BM of irradiated mice after 0, 7th and 10th day of irradiation. LD50(30) for C3H/J mice was 7.3 Gy and the dose modifying factor (DMF) of 5-HTP + AET combination was 1.76. On the contrary, pretreatment with this combination did not protect the mammary carcinoma transplanted in C3H/J mice, when exposed to 80 Gy soft X-rays.

5-Hydroxytryptophan↗

Ontogenetic and comparative analysis of LDH isozymes in the three species of Indian major carp.

Expression patterns of lactate dehydrogenase (LDH) isozyme were investigated in embryonic and post embryonic stages of Labeo rohita, Cirrhinus mrigala and Catla catla using starch gel electrophoresis. Species specific and differential enzyme locus (gene) expression patterns were found in LDH up to 18th hr of study. The isozyme up to 36th hr after fertilization seemed to be completely active and showed electrophoretic patterns very similar to those of the adults. Comparative analysis of the isozyme of the three species permitted species identification even during the embryonic stages when it is impossible to identify on morphological characters only. Also, the genetic studies indicated different taxonomical and evolutionary histories of the species.

Animals↗

Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery.

p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections.

Albumins↗

Enhanced intracellular delivery of methotrexate by a receptor-mediated process.

In the present investigation we have described a method of enhancing the uptake of methotrexate by macrophages. This enhanced uptake was mediated by endocytosis through the "scavenger receptor" system which recognized maleylated bovine serum albumin. Experimental evidence showed that macrophages internalized methotrexate coupled to maleylated bovine serum albumin through a saturable process at 37 degrees C leading to an eightfold higher concentration of cell-associated methotrexate compared to the free drug. Following uptake, the drug conjugate was degraded in the lysosomes leading to intracellular release of a pharmacologically active form of methotrexate. When administered to macrophages infected with Leishmania mexicana amazonensis, the drug conjugate could eliminate the intracellular amastigotes more efficiently than the free drug. The leishmanicidal effect of the drug conjugate was inhibited in the presence of excess maleylated bovine serum albumin and lysosomal inhibitors such as chloroquine and monensin. Addition of folinic acid to the medium also prevented the elimination of the amastigotes by the drug conjugate. These results suggested that the scavenger receptor-mediated endocytosis of the drug conjugate led to enhanced transport and intracellular release of a pharmacologically active form of methotrexate resulting in more efficient killing of the amastigotes compared to the free drug. This modality of delivering drugs selectively to macrophages might have utility in the chemotherapy of macrophage-associated disorders in general.

Albumins↗

Non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in the elderly.

Cases of gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs (NSAIDs) were analysed. Forty per cent of the 92 cases admitted with gastrointestinal bleeding were found to be on NSAIDs. Sixty per cent of the cases on NSAIDs had a preceding history of dyspepsia or ulcer disease and its complications. Forty per cent presented with spontaneous bleeding. We discuss some of the aspects of the management of these cases in clinical practice.

Aged↗

ACE inhibitors and diuretics causing hypokalaemia.

Angiotensin-converting enzyme (ACE) inhibitors and diuretics are known to cause hyperkalaemia. We undertook a prospective analysis over a period of six months of patients admitted under our care. Of 217 patients, 39 (18 per cent) were admitted with congestive cardiac failure/left ventricular failure. Of these 39 patients, 21 (54 per cent) were prescribed ACE inhibitors. Seven of these 21 patients subsequently developed hypokalaemia. This was irrespective of the type or dose of the diuretic but seemed to be related to the dose of the ACE inhibitor. In three cases the hypokalaemia was corrected by the addition of a potassium-sparing diuretic; in two cases a potassium supplement was added; and in the other three an increase in the dose of the ACE inhibitor for the resistant heart failure corrected the potassium deficit. This study shows that one should be alert to both hyperkalaemia and hypokalaemia when using a combination of ACE inhibitors and diuretics.

Aged↗

A clinical study of adult leukaemias.

The incidence of adult leukaemias, their response to therapy and the complications of therapy were studied in 121 cases over seven years (1981-1987). All cases were followed up till recovery or death for periods ranging from seven days to seven years. Adult leukaemias accounted for 2.56% of all admissions due to malignancies. There were 21 cases of acute lymphoblastic leukaemia, 61 of acute myelogenous leukaemia, 36 of chronic myelocytic leukaemia and 3 chronic lymphocytic leukaemia. All received aggressive combination chemotherapy. Remission could be achieved in 57% to 60% of cases. Infection (34%), bleeding (34%), and central nervous system involvement (25%) were the complications during therapy. The cause of death was ascertained in 87 of 90 deaths by a detailed postmortem. Haemorrhage (34.5%), infection (31%) and uncontrolled leukaemia (22%) were the leading causes, either singly or in combination. Some of the uncommon causes of death were fulminant hepatic failure, coronary artery disease, gangrene of the colon and disseminated tuberculosis.

Adolescent↗

Selective delivery of drugs to macrophages through a highly specific receptor. An efficient chemotherapeutic approach against leishmaniasis.

Methotrexate (Mtx) conjugated with maleylated bovine serum albumin (Mtx-MBSA) was taken up and degraded by cultured hamster peritoneal macrophages through the polyanion binding site for acetylated low density lipoprotein. Mtx-MBSA also eliminated intracellular amastigotes of Leishmania donovani in cultured hamster peritoneal macrophages about three times more efficiently than free Mtx. The antileishmanial effect of Mtx-MBSA on parasitized macrophages was blocked by MBSA, lysosomal inhibitors (chloroquine and monensin), and metabolic antagonists of Mtx (folic and folinic acids). The primary sites of accumulation of radioactivity of injected 125I-labeled Mtx-MBSA were the macrophage rich tissues, viz. liver and spleen. These results suggest that Mtx-MBSA would ensure rapid and effective killing of intracellular parasites harbored by macrophages. Furthermore, these results also indicate the feasibility of a general approach for rapid intracellular delivery of desired agents to macrophages for various purposes.

Animals↗

Receptor-mediated drug delivery to macrophages in chemotherapy of leishmaniasis.

Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the "scavenger" receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.

Albumins↗