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Biomedical subjects

B R Rao

Publications and source records attributed to B R Rao.

At least 37 records · Page 2Linked to original sources
PubMed1997

Spinal intramedullary cysticercosis.

OBJECTIVE: Spinal intramedullary cysticercosis is an uncommon manifestation of neurocysticercosis. We review our experience with eight cases of intramedullary cysticercosis. METHODS: Eight patients who were surgically treated for spinal intramedullary cysticercosis between 1982 and 1991 were retrospectively reviewed, and the final outcomes were assessed. RESULTS: In six patients, the cysticercosis involved the thoracic cord, whereas in the other two, the cysticercosis was cervical in location. Only one patient had multiple soft tissue calcifications, as revealed by plain radiography. Myelography indicated an intramedullary lesion in each of seven patients; two of the seven patients had partial myelographic block, suggesting the segmental nature of the lesion. Cerebrospinal fluid studies were noncontributory. One patient had three cysts, whereas the other seven had one cyst each. Four patients had adjacent soft purulent materials, which were revealed by histopathological examination to be granulation tissue. The neurological statuses of seven patients improved after surgery. Six patients were followed up for a mean of 30.6 months (3 mo-5 yr). Three could resume their previous occupations, two others could manage their daily activities, and one required only minimal assistance for daily activities. CONCLUSION: The outcome of intramedullary cysticercosis is not as dismal as reported earlier, and patients with paraplegia also have favorable outcomes. A preoperative diagnosis of cysticercosis can be suspected in an endemic area in the presence of multiple soft tissue calcifications and segmental lesions revealed by myelography or magnetic resonance imaging studies.

Activities of Daily Living↗
PubMed1997

Circadian variation in urinary excretion of ciprofloxacin after a single-dose oral administration at 1000 and 2200 hours in human subjects.

Ciprofloxacin is routinely prescribed to treat a variety of infections, including those of the urinary tract. To achieve optimum therapeutic benefits of the drug, all of the factors which influence its pharmacokinetics and effectiveness need to be determined. This study investigated the urinary excretion kinetics of ciprofloxacin upon oral administration of a single dose of 250 mg at 1000 or 2200 h in 12 healthy human subjects in a crossover design. The urine samples were analyzed for unchanged ciprofloxacin by a sensitive high-performance liquid chromatography method. A significant decrease in the rate and extent of ciprofloxacin excretion following 2200 h (109.59 versus 53.8 mg [P < 0.05]) administration was observed. This result may be due to circadian changes in the factors affecting renal excretion and also probably metabolism of ciprofloxacin.

Administration, Oral↗
PubMed1996

Multidrug resistance-modifying components in human plasma with potential clinical significance.

P-Glycoprotein (P-gp) and multidrug resistance protein (MRP) are plasma membrane associated proteins which can confer multidrug resistance (MDR) to cancer cells by lowering the intracellular amount of drug. Although clinical trials with MDR-reverting agents have been initiated, not much attention has been paid to blood components which may modulate the activity of P-gp or MRP. The present investigation was performed to identify and characterize blood components which may influence the drug content and the drug cytotoxicity of MDR cells. Human plasma, from healthy volunteers, was tested for its effects on the daunorubicin (DNR) accumulation and cytotoxicity in the MDR cell lines SW-1573/2R160 (2R160) and GLC4/ADR containing P-gp and MRP, respectively. The data were compared to the effects observed in wild-type cells. MDR-modifying plasma components were isolated by extraction procedures and characterized using ultrafiltration, high-performance liquid chromatography (HPLC) and mass spectrometry. An increase in the proportion of plasma in the culture medium led to a reduction of the ratio between the DNR content of wild-type and corresponding MDR cells. At 100% plasma we observed an increase in the cellular DNR content of 2R160 cells, which was 10-30% (median 18%) of the maximum possible increase induced by well-known MDR-reverting agents, such as verapamil (for GLC4/ADR cells: 10-20%, median 15%). The DNR cytotoxicity in MDR cells also increased with an increasing amount of plasma included in the culture media. There was neither an increase in the cellular DNR content nor an effect on the DNR cytotoxicity in wild-type cells. Plasma extract analysis by HPLC showed a major peak which increased the DNR content of MDR cells. The HPLC column retention time of this fraction was identical to that of a standard of cortisol and it was further confirmed to be cortisol using mass spectrometry. Moreover, inclusion of a standard of cortisol in culture media induced a similar effect. We analyzed the data for one of the plasma pools and found that blood cortisol was responsible for the MDR-modulating effect only for 35% of the effect of 100% plasma. Other plasma components were responsible for the remaining modulation effect on MDR cells. In conclusion, the DNR pumping activity of P-gp and MRP is inhibited by human plasma, resulting in 10-30% of the maximum possible increase in cellular drug content. Based on cellular pharmacokinetic calculations this percentage will most likely increase at clinical levels of drug resistance (reaching 40-50%). In one sample blood cortisol accounted for 35% of the effect of plasma on the DNR content in MDR 2R160 cells. These data show the need for additional studies to test plasma samples for their MDR modulating effects before the administration of MDR-reverting agents in chemotherapy. The data suggest that the effectiveness of chemotherapeutic drugs may be enhanced when administered in accordance with the circadian peak of endogenous corticoids.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene.

The promoter of the cell cycle regulated histone FO108 H4 gene is mediated by two in vivo protein/DNA interaction domains, sites I and II. We have shown previously that site II mediates the cell cycle controlled enhancement of H4 gene transcription at the G1/S phase boundary. Here we show that site I, an element containing both G-rich and ATF-like consensus sequences, confers maximal levels of transcription in proliferating cells. By the combined application of gel shift assays with site-directed mutagenesis, DNase I footprinting, oligonucleotide competition, in vitro expression of recombinant proteins, and specific antibody supershift studies, we demonstrate that the proximal G-rich sequence within site I interacts with the transcription factor Sp1, while the distal portion of site I interacts with members of the ATF family of proteins, including ATF-1. In vitro transcription studies as well as expression assays of transiently and stably transfected genes in HeLa cells reveal that the deletion of site I causes a dramatic decrease in expression. Mutation of the Sp1 element, which abolishes Sp1 binding, results in a 6-10-fold reduction in reporter activity. In addition, overexpression of Sp1 in Sp1-deficient cells results in the dramatic activation of the histone promoter. In contrast, mutation of the asymmetric ATF binding site, located distally within site I, has a more limited effect upon expression. Interestingly, the contribution of the Sp1 site to maximal transcription was cell type dependent. Thus, we demonstrate that the Sp1 binding site of the site I histone H4 promoter in particular is critical for maximal expression in living cells and postulate that this site may act to amplify the cell cycle response.

Base Sequence↗
PubMed1995

Absence of a pharmacokinetic interaction between quinidine and diazepam.

Influence of diazepam on the pharmacokinetics of quinidine was studied in eight healthy human volunteers by administering 250 mg of quinidine sulphate either alone or in combination with 10 mg diazepam in a cross-over study. Quinidine in the biological samples was estimated fluorimetrically. Comparison of various pharmacokinetic parameters of quinidine (Cmax 2.165 +/- 0.457 vs 2.239 +/- 0.338 micrograms/ml, Tmax 2 +/- 0.71 vs 2.13 +/- 0.58 h, T1/2 7.004 +/- 1.302 vs 7.82 +/- 1.63 h, Cls/f 153.63 +/- 45.65 vs 134.87 +/- 31 ml/h/kg, AUC0-alpha 22.131 +/- 6.118 vs 24.321 +/- 4.924 micrograms.h/ml) by means of a two tailed t-test revealed no significant (p > 0.05) effect of diazepam on quinidine disposition kinetics.

Adolescent↗
PubMed1995

Diurnal oscillations in the serum and salivary levels of quinidine.

The pharmacokinetics of quinidine in healthy subjects was studied through serum and salivary compartments by orally administering 250 mg of quinidine sulphate (CAS 50-54-4) either at 10:00 or 22:00 h. Quinidine concentrations in the biological samples were determined fluorimetrically. None of the pharmacokinetic parameters obtained from serum levels showed any significant time dependent changes. However, prolongation in tmax and lowering of Ka and t1/2 was noticed after nocturnal drug administration when the parameters were computed from salivary levels. Also, significant (p < 0.05) lowering of saliva/serum (SL/SR) ratios was observed after 22:00 h drug dosing. Temporal alterations in quinidine secretion into saliva could be the reason for the above changes. Alteration of salivary quinidine levels in turn could be caused by altered protein binding in serum and/or the time dependent changes in the permeability of biological membranes involved in the production of saliva.

Adolescent↗
PubMed1994

Lipid peroxidation product in bile from patients with carcinoma of the gallbladder: a preliminary study.

Samples of gall bladder bile from patients with and without carcinoma of the gallbladder were examined for lipid peroxidation (free radical oxidation) products. 4-hydroxynonenal (HNE) was found in higher concentration in the bile of patients with carcinoma of the gall bladder. There was also a highly significant difference in the concentration of HNE among carcinoma of the gall bladder, cholelithiasis and control group of patients with miscellaneous abdominal disorders. This is the first study of lipid peroxidation in carcinoma of the gall bladder.

Aldehydes↗
PubMed1994

Phase II trial of flutamide in advanced ovarian cancer: an EORTC Gynaecological Cancer Cooperative Group study.

New active non-toxic therapeutic regimens are warranted in ovarian cancer relapsing after platinum-based chemotherapy. Some investigators have determined that androgen receptors predominated over oestrogen and progesterone receptors in untreated common epithelial ovarian cancer tissue cytosols. In an effort to test its antitumoural activity, 68 pretreated patients with epithelial ovarian cancer were given flutamide 750 mg/day orally for at least 2 months. Of 32 patients who received a minimum of 2 months of therapy, pretreated with at least one platinum-based chemotherapy, and a median of two chemotherapy regimens, two (6.3%) objective responses (one complete and one partial) and nine (28%) disease stabilisations were observed; these lasted 44 and 72 weeks, respectively (for the complete and partial response), and for a median of 24 weeks for stabilisations (range 12-48+). Nausea and vomiting were the most frequent side-effects. These occurred in 19/55 (34.5%) patients evaluable for toxicity. Flutamide has to be considered ineffective in patients extensively pretreated with chemotherapy, and it is not devoid of side-effects.

Adult↗
PubMed1993

An immunohistochemical evaluation of androgen and progesterone receptors in ovarian tumors.

To visualize the heterogeneity of androgen receptor (AR) and progesterone receptor (PR) expression in ovarian tumors, 61 specimens were studied immunohistochemically using specific mouse monoclonal antibodies. The tested ovarian tumors included ovarian carcinomas of serous, mucinous, endometrioid, undifferentiated, and clear cell types as well as borderline epithelial tumors, mucinous cystadenomas, granulosa cell tumors, metastatic ovarian tumors, and one case of immature teratoma. Sixty-seven percent of ovarian carcinomas expressed AR, while 46% of the ovarian carcinomas expressed PR. In addition, the three tested borderline epithelial tumors were AR positive. Androgen receptor and PR were primarily localized in the nuclei of ovarian tumor cells. In three tumors focal staining of intervening stroma cells was observed. Interestingly, 35 of the granulosa cell tumors expressed PR as well as AR. All tumor types displayed a wide range in their proportions of AR- and PR-positive tumor cells. A poor correlation, however, was observed when semiquantitative immunohistochemical AR staining results on 17 ovarian carcinomas were compared with biochemical cytosol AR estimations using the dextran-coated charcoal method. Our study indicates that AR as well as PR is expressed by a substantial proportion of ovarian borderline and malignant tumors and that there is a strong heterogeneity in expression of AR and PR. It is possible to evaluate the prognostic significance of these receptors in ovarian cancers on fresh-frozen tumor specimens using a simple immunohistochemical technique.

Carcinoma↗
PubMed1992

The metastatic potential of rat prostate tumor variant R3327-MatLyLu is correlated with an increased activity of N-acetylglucosaminyl transferase III and V.

Enzyme activities of N-acetylglucosaminyltransferase (GlcNAc-Tase) I-V involved in N-linked complex-type carbohydrate synthesis were determined in a non-metastatic hormone-dependent rat prostate tumor (R3327-H) and a related, hormone-independent variant metastasizing to lymph nodes and lungs (R3327-MatLyLu). In the metastasizing variant a significantly increased activity of both GlcNAc-Tase III and GlcNAc-Tase V was observed, whereas the activities of GlcNAc-Tase I and II were essentially unchanged. The increase in activity of GlcNAc-Tase III is particularly noteworthy since it indicates that elevated expression of this enzyme cannot be considered as an exclusive marker of hepatic malignancy.

Animals↗
PubMed1992

Estrogenic action of commonly used fragrant agent citral induces prostatic hyperplasia.

A rat model for benign prostatic hyperplasia in man (BPH) was investigated. Citral treatment of male Copenhagen rats for 4 months via the transdermal route resulted in a marked hyperplasia of glandular epithelium and interglandular stroma in the ventral prostate. Despite the cellular hyperplasia there was not a significant increase in prostate weight. Investigations of the mechanism of action of citral showed that application of citral directly to the vagina in female, ovariectomized rats resulted in an increased proliferation of vaginal epithelium and a significant increase in the BrdUrd incorporation in vaginal epithelial cells, in short a similar effect to that of estrogen application. In an in vitro assay citral proved to inhibit estrogen binding to estrogen receptors, while no such inhibition was observed with testosterone for androgen receptors. These observations together with the estrogen implication in the BPH and the reported incidence of gynecomastia following exposure to geraniol, a precursor of citral, strongly suggest that the prostatic hyperplasia-inducing capacity of citral may be due to its estrogenic action.

Acyclic Monoterpenes↗
PubMed1992

Consideration of the use of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5- alpha-androstan-3-one (4MA), a 5 alpha-reductase inhibitor, in prostate cancer therapy.

We investigated the effect of 17 beta-N,N-diethylcarbamoyl-4-methyl-4aza- 5 alpha-androstan-3-one (4MA), a 5 alpha-reductase inhibitor, on growth inhibition of androgen-sensitive rat prostatic tumour (R3327-H) and correlated it with changes in weight of normal androgen target tissues and with levels of androgens. Groups of male Copenhagen rats were treated for 28 days with a daily injection of various, increasing doses of 4MA (0.01-4.0 mg/day) and the results were compared with control (vehicle-treated) and with castrated animals. 4MA decreased tumour growth rate in a dose-dependent manner, which was reflected in a decreased incorporation of BrdUrd in DNA of glandular epithelial cells in the tumour. Normal prostate wet weight was also decreased after high-dose 4MA treatment while serum testosterone levels were not affected by 4MA treatment. Contrary to expectations, however, tissue levels of dihydrotestosterone in tumour and ventral prostate were still considerable in 4MA-treated animals. The tumour-inhibiting action of 4MA, therefore, has to be interpreted as not being purely due to 5 alpha-reductase inhibition. On the other hand, it was not possible to demonstrate any direct tumoricidal effect of 4MA in vitro. The relevance of these findings in terms of the endocrine mechanism of action of 4MA on tumour growth is discussed.

5-alpha Reductase Inhibitors↗
PubMed1992

Progression delay of prostate tumor skeletal metastasis effects by bisphosphonates.

Prostate tumor cell metastasis to the axial skeleton was induced in male Copenhagen rats using the intravenous injection of syngeneic metastatic R3327-MATLyLu tumor cells and concomitant caval vein clamping. The proliferation of tumor cells in the lumbar region was monitored by the progression, within 19 days post tumor cell injection, of hindleg paralysis which appeared in these animals. Histology confirmed the presence of tumor cells within the lumbar spine in 100% of cases displaying hindleg paralysis. Treatment with either of the bisphosphonate drugs, Cl2MDP or APD, suppressed and delayed the development of hind leg paralysis. Bisphosphonate treatment may be expected to delay the onset of axial skeletal metastasis effects in prostate cancer patients.

Animals↗
PubMed1992

Initial intensive therapy for multibacillary leprosy patients--in retrospect.

We analysed the results of 4845 multibacillary (MB) patients being treated with multidrug treatment (MDT) in the Srikakulam District of Andhra Pradesh, India. Of these, 2309 (47.7%) patients were given an initial 14-day intensive therapy with rifampicin, clofazimine and dapsone, followed by the WHO recommended pulse therapy. The rest of the cases were given only pulse therapy. The improvement in terms of bacteriological clearance and the proportion of cases declared released from treatment (RFT) was found to be significantly higher among patients treated with only pulse therapy. Clinic attendance was found to be better and more regular in patients treated with intensive therapy, and no relapses were seen with either therapy. The implications of these findings on the operational aspects of programme implementation are discussed.

Humans↗
PubMed1992

Chronopharmacokinetics of rifampicin.

Chronopharmacokinetics of rifampicin was studied in four healthy adult male human volunteers after drug (2.0 g) ingestion at 6.00, 12.00, 18.00 and 24.00 hr. The absorption rate constant was found to be lower and the time to reach peak concentration was longer after drug administration at 24.00 hr than at other dosing times. A second peak was observed in all individual volunteers between 6-12 hr after drug dosing at 24.00 hr. This may be due to the influence of biliary rhythms on the disposition kinetics of rifampicin.

Adult↗