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Biomedical subjects

S Dhar

Publications and source records attributed to S Dhar.

At least 19 recordsLinked to original sources
PubMed1997

Differential activity of Cremophor EL and paclitaxel in patients' tumor cells and human carcinoma cell lines in vitro.

BACKGROUND: Previous studies indicate that Cremophor EL (CEL), the excipient for Taxol, a clinical preparation of paclitaxel, has biologic properties per se. METHODS: The cytotoxic activity of Taxol and its solvents CEL/ethanol, paclitaxel in ethanol, and 14 other cytotoxic drugs was investigated in vitro in 10 human carcinoma cell lines and 183 tumor samples from patients with tumors of various types. Cytotoxicity was determined by the fluorometric microculture cytotoxicity assay. RESULTS: In the cell lines, Taxol was generally more active than paclitaxel; this may have been due to an additive effect of the diluent. This activity was pronounced in sublines expressing tubulin-associated and P-glycoprotein-mediated drug resistance, indicating involvement of these mechanisms in paclitaxel resistance and their modulation by CEL. Taxol and paclitaxel were highly cross-resistant to other tubulin-active agents, whereas the low cytotoxic effect of CEL seemed unrelated to other drugs. In the samples from patients, Taxol was less active than in the cell lines but showed a differential activity that corresponded reasonably well with that in the clinic. CEL and Taxol were similarly active, indicating that paclitaxel did not add substantially to the activity of Taxol. CONCLUSIONS: Whereas the cell line data clearly confirmed the well-known properties of paclitaxel, a more valid model using tumor cells from patients demonstrated that CEL significantly contributes to the efficacy of Taxol in vitro. The clinical relevance of this finding remains to be elucidated.

Antineoplastic Agents↗
PubMed1997

Serodiagnosis of Babesia equi infection--a comparison of Dot-ELISA, complement fixation test and capillary tube agglutination test.

The present study aimed to develop Dot-ELISA, complement fixation test (CFT) and capillary tube agglutination test (CAT) for serodiagnosis of Babesia equi infection and to compare their sensitivity with each other. For this study, sequential serum samples were collected from four donkeys experimentally infected with B. equi up to 90 days post infection (P.I.). B. equi antigen was prepared from the blood of a donkey showing more than 80% parasitaemia. Dot-ELISA, CF and CA tests were standardized as per the standard method. While performing CFT, it was observed that CFT standardized for the donkey system could not be applied to the horse system, and different units of the same antigen and complement were required for each. Dot-ELISA detected antibodies from 3-6 days P.I. onwards, whereas CF and CA tests could detect antibodies from the 6th day P.I. indicating that Dot-ELISA is the more sensitive. The efficacy of these three tests was also determined by testing 211 field serum samples of apparently healthy horses. By Dot-ELISA 49.76%, by CAT 42.18% and by CFT 27.86% of the serum samples were found positive. As the results of Dot-ELISA and CAT are comparable, it is proposed that CAT may be used as a screening test.

Agglutination Tests↗
PubMed1997

Cytotoxic activity of topotecan in human tumour cell lines and primary cultures of human tumour cells from patients.

The cytotoxic activity and cross-resistance pattern of the novel topoisomerase I inhibitor topotecan (Topo) were investigated in ten cell lines, representing different mechanisms of cytotoxic drug resistance, and in 218 fresh human tumour samples using the fluorometric microculture cytotoxicity assay (FMCA). Resistance to Topo in the cell lines was associated with expression of the multidrug resistance-associated protein (MRP), whereas the cell lines with P-glycoprotein (P-gp), topoisomerase II and glutathione-associated resistance did not show decreased sensitivity to the drug. Topo was more active in haematological than in solid tumour samples, but substantial activity was observed in carcinomas of the ovary and breast, sarcoma and childhood solid tumours. Cross-resistance to standard drugs representing different mechanisms of action was generally low in patient cells. The effect of Topo was better after longer exposure, but this time-dependent effect was largely abolished when adjustment for in vitro exposure was made. Topo showed activity both in proliferative and non-proliferative cell systems. The results indicate that Topo is insensitive to major mechanisms of resistance except for MRP. Proliferation does not seem to be necessary for the effect of Topo, and no superiority for protracted dosing schedules was observed. The results also suggest that, for example, leukaemias, lymphomas, sarcomas and childhood solid tumours may be suitable targets for future phase II trials.

Camptothecin↗
PubMed1996

Cytotoxic activity of calcein acetoxymethyl ester (Calcein/AM) on primary cultures of human haematological and solid tumours.

The aim of this study was to determine the in vitro cytotoxicity of calcein acetoxymethyl ester (Calcein/AM) on primary cultures derived from solid and haematological human tumours. Calcein/AM is a fluorescent dye that localises intracellularly after esterase-dependent cellular trapping and which has shown cytotoxic activity against various established human tumour cell lines at relatively low concentrations. The semi-automated fluorometric microculture cytotoxicity assay, based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate to fluorescein, in microtitre plates was used for the evaluation of Calcein/AM activity in tumour cell suspensions from patients. The cytotoxicity was measured as a survival index (SI), defined as the fluorescence as a percentage of control cultures. A total of 163 evaluable samples from various tumours were tested with continuous drug exposure. The activity of Calcein/AM was compared with representatives of six major classes of standard chemotherapeutic drugs. Calcein/AM was found to induce concentration-dependent decreases in the SI of both haematological and solid tumour cells. The ratio of solid over haematological tumour activity increased at a rate that was concentration dependent. Although it was relatively less active than cisplatin against solid tumours, Calcein/AM showed higher solid tumour activity compared to leukaemic specific agents (cytarabine and amsacrine), vincristine and doxorubicin (Dox). Among the solid tumours tested, childhood tumours, non-small cell lung cancer and sarcomas were the most sensitive to Calcein/AM. The best correlation between SI values was seen between Calcein/AM and Dox, with weaker correlations to representatives of antimetabolites, platinum compounds, topoisomerase II inhibitors, tubulin interactive agents and alkylators. Non-cytotoxic concentrations of cyclosporin A significantly potentiated calcein-induced cytotoxicity. The results show that Calcein/AM is differentially active against haematological tumours, but with substantial activity against solid tumours. The drug may represent a new class of anticancer compound with a unique means of drug delivery.

Antineoplastic Agents↗
PubMed1996

Anti-cancer drug characterisation using a human cell line panel representing defined types of drug resistance.

Differential drug response in a human cell line panel representing defined types of cytotoxic drug resistance was measured using the non-clonogenic fluorometric microculture cytotoxicity assay (FMCA). In total 37 drugs were analysed; eight topoisomerase II inhibitors, eight anti-metabolites, eight alkylating agents, eight tubulin-active agents and five compounds with other or unknown mechanisms of action, including one topoisomerase I inhibitor. Correlation analysis of log IC50 values obtained from the panel showed a high degree of similarity among the drugs with a similar mechanism of action. The mean percentage of mechanistically similar drugs included among the ten highest correlations, when each drug was compared with the remaining data set, was 100%, 92%, 88% and 52% for the topoisomerase II inhibitors, alkylators, tubulinactive agents and anti-metabolites respectively. Classification of drugs into the four categories representing different mechanisms of action using a probabilistic neural network (PNN) analysis resulted in 29 (91%) correct predictions. The results indicate the feasibility of using a limited number of cell lines for prediction of mechanism of action of anti-cancer drugs. The present approach may be well suited for initial classification and evaluation of novel anti-cancer drugs and as a potential tool to guide lead compound optimisation.

Antineoplastic Agents↗
PubMed1996

Drug related involvement of specific sites in fixed eruptions: a statistical evaluation.

Different drugs produce fixed eruptions over different parts of the body. However, the significance of preferential site involvement in fixed eruptions due to specific drugs has not been statistically evaluated. One hundred and twenty five patients of fixed drug eruption (FDE) were studied to examine this question. Different sites affected by individual drugs were classified as lips alone, genitalia alone, lips and genitalia together, trunk alone, trunk and limbs together, and generalized. Statistical analysis was carried out for 7 common drugs causing FDE in 5 or more patients. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common offender for FDE (32.8%), followed by analgin (12%), tetracycline (8%), pyrazolones (8%), metronidazole (6.4%), ciprofloxacin (5.6%), and phenytoin sodium (4%). Major sites involved by FDE were trunk and limbs (24%), lips alone (20.8%), genitalia alone (20%), generalised (14.4%), lips and genitalia together (11.2%), and trunk alone (8.8%). Seventy-two (57.6%) patients had multiple lesions; 33 (42.4%) had single lesions. Involvement of mucocutaneous junctions of lips and genitalia by FDE was frequently caused by cotrimoxazole and tetracycline; trunk and limbs, by analgin and pyrazolones. Generalised eruptions were commonly caused by cotrimoxazole and phenytoin. The present statistical analysis confirms the clinical impression that genitalia alone are frequently involved in FDE due to tetracyclines (p < 0.001). FDE over trunk and limbs was significantly associated with analgin (p < 0.001), and generalised eruptions, with phenytoin sodium (p < 0.001). The association of FDE over lips with cotrimoxazole was statistically not significant.

Adolescent↗
PubMed1996

Fixed drug eruption due to ciprofloxacin.

We describe seven patients with fixed drug eruption (FDE) due to ciprofloxacin, five confirmed by rechallenge. These cases make up 8.75% of all cases of FDE seen by us during 1992-93. Isolated, and striking involvement of the lips was seen in two patients. To our knowledge, only a single case of FDE to ciprofloxacin previously has been reported. Our experience suggests that, with widespread use, ciprofloxacin could become one of the common drugs causing FDE.

Adult↗
PubMed1996

Prevalence of tuberculosis in Kishtwar Tehsil of Jammu region in Jammu and Kashmir State.

A study of prevalence of tuberculosis in Kishtwar tehsil of Jammu region was conducted from June 1991 to May 1992. A total of one thousand two hundred ninety-eight rural as well as urban population suffering from various types of lung diseases was studied for prevalence of tuberculosis and a sizeable number (98) of patients were found to be positive of various types of tuberculosis, viz, pulmonary tuberculosis, tuberculous pleural effusion and miliary tuberculosis. Of the population studied 7.55% were found to be positive for tuberculosis and among them 88.76% patients were anaemic and the commonest type of anaemia was normocytic normochromic and normocytic hypochromic. The ESR was raised in almost of all the patients. Of the population, 80.61% were seen to be positive on skiagram chest and 58.16% were found to be positive on other diagnostic tests like Mantoux's tests, sputum for acid-fast bacilli, etc. Mantoux's test was positive in 27.55% cases and sputum was positive in 30.61% cases. All the cases studied were subjected to special investigations. The changes in parameters are consistent with the diagnosis of tuberculosis. Large family size, poverty, excessive smoking, illiteracy, etc, are the major contributing factors.

Adolescent↗
PubMed1995

Cytotoxic effect of calcein acetoxymethyl ester on human tumor cell lines: drug delivery by intracellular trapping.

Calcein acetoxymethyl ester (calcein/AM) and some related cellular dyes with a cytoplasmic distribution were investigated with respect to cellular hydrolysis, accumulation, efflux and cytotoxicity in a panel of established human cell lines, including multidrug resistant (MDR) phenotypes. At 0.1-1 micrograms/ml, calcein/AM was highly cytotoxic against several cell lines, even after short-term exposure (30 min). Calcein/AM induced no immediate loss (3 h) of membrane integrity and the drug was more active against low compared with high density plated cells. In cell lines with the MDR phenotype and in the renal carcinoma cell line ACHN, the drug was considerably less active. Non-esterified calcein had no effect and calcein/AM was significantly more potent than other structurally related fluorescein analogs and AM esters tested. Although MDR cell lines showed a decreased cellular hydrolysis and accumulation of the dye, there was no strict relationship between cytoplasmic calcein exposure and cytotoxic activity. The rate of efflux was low in the two most sensitive cell lines, the human lymphoma U-937-GTB and its vincristine (vcr) resistant subline U-937/vcr10, while the remaining cell lines showed similar biphasic efflux patterns, including cell lines of the MDR phenotype. The results show that calcein/AM has cytotoxic activity against human tumor cell lines at low concentrations. The effect appears dependent on the intracellular trapping of the drug, although the specific cellular target remains unknown. Due to its cytotoxic efficacy and unique principle of cellular drug delivery, further investigation of calcein/AM and related compounds as potentially new anticancer agents seems warranted.

Antineoplastic Agents↗
PubMed1995

Melkersson-Rosenthal syndrome in India: experience with six cases.

Six patients with Melkersson-Rosenthal syndrome (M-R syndrome) were presented. Their ages varied from 20 to 60 years; age at onset was between 15 and 50 years. In all 6 patients, swelling started first over the lower lip. Associated facial palsy, facial edema, and scrotal tongue were found in three, four and one patients, respectively. Lip biopsies from 5 patients failed to show any granuloma. Intralesional corticosteroids produced mild regression of labial swelling in two patients after 6 injections. In one patient, near total reduction of labial swelling and facial edema was achieved after 5 months of clofazimine treatment. However, there was no improvement of facial palsy. To the best of our knowledge, this is the largest series of M-R syndrome reported from India.

Adult↗
PubMed1995

Clinical pattern of cutaneous drug eruption among children and adolescents in north India.

Various types of cutaneous drug eruptions and the incriminating drugs were analyzed in 50 children and adolescents up to 18 years of age (34 or 65% boys, 16 or 32% girls). Thirteen (26%) patients had a maculopapular rash, 11 (22%) a fixed drug eruption (FDE), 10 erythema multiforme (EM), 6 (12%) toxic epidermal necrolysis (TEN), 5 (10%) Stevens-Johnson syndrome (SJS), 3 (6%) urticaria, and 2 (4%) erythroderma. The incubation period for maculopapular rashes, SJS and TEN due to commonly used antibiotics and sulfonamides was short, a few hours to two to three days, reflecting reexposure, and for drugs used sparingly such as antiepileptics and antituberculosis agents, was approximately one week or more, suggesting a first exposure. Antibiotics were responsible for cutaneous eruptions in 27 patients, followed by antiepileptics in 17, analgin in 4, and metronidazole and albendazole in 1 each. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common antibacterial responsible for eruptions (11 patients), followed by penicillin and its semisynthetic derivatives (8 patients), sulfonamide alone (3 patients), and other antibiotics (4 patients). Antiepileptics were the most frequently incriminated drugs in EM, TEN, and SJS. The role of systemic corticosteroids in the management of SJS and TEN is controversial. We administered prednisolone or an equivalent corticosteroid 2 mg/kg/day for 7 to 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗