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Biomedical subjects

B R Rao

Publications and source records attributed to B R Rao.

At least 19 recordsLinked to original sources
PubMed2004

Ascorbyl palmitate vesicles (Aspasomes): formation, characterization and applications.

Vesicles with biological activity or with a targeting function in addition to carrier properties will have an added advantage. Vesicles prepared with amphiphiles having antioxidant property may have potential applications towards disorders implicated with reactive oxygen species. Ascorbyl palmitate (ASP) was explored as bilayer vesicle forming material. It formed vesicles (Aspasomes) in combination with cholesterol and a negatively charged lipid (dicetyl phosphate). Aspasomes were prepared by film hydration method followed by sonication in which aqueous azidothymidine (AZT) solution was encapsulated in aqueous regions of bilayer. Aspasomes were obtained with all compositions containing 18-72 mol% cholesterol. Differential scanning calorimetric data of aspasome dispersion and anhydrous mixtures of ascorbyl palmitate, cholesterol and dicetyl phosphate confirm the formation of bilayered vesicles with ascorbyl palmitate. Cholesterol content in aspasome did not exhibit any relation with vesicle size, zeta potential or percent entrapment. A substantial change in release rate of azidothymidine from aspasome was noticed on varying the proportion of cholesterol. Release rate and cholesterol content in Aspasomes did not exhibit any relation. A preparation with 45 mol% of cholesterol showed maximum retardation in release rate, than other compositions. The change in capture volume with time (latency) was studied for 8 h and with such a short duration study it was difficult to predict long term stability of these vesicles. But release experiments do indicate stability up to 18 h. Percent reducing activity of aspasome was estimated by measuring the absorbance of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) at 517 nm after addition of test antioxidant samples. These studies revealed that the antioxidant potency of ascorbyl moiety is retained even after converting ascorbyl palmitate into vesicles (Aspasomes). The antioxidant potency of Aspasomes was assessed by measuring the protection offered by this preparation against quinolinic acid induced lipoperoxidation of whole human blood in vitro, where in the lipoperoxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) levels. Aspasome rendered much better antioxidant activity than ascorbic acid. Transdermal permeation of aspasomal AZT, ASP-AZT aqueous dispersion and AZT-solution across excised rat skin was investigated in vitro using Franz diffusion cell. Permeation of aspasomal AZT was much higher than the other two preparations. However, ASP-AZT aqueous dispersion has also enhanced permeation of AZT significantly over the AZT-solution, indicating skin permeation enhancing property of ascorbyl palmitate.

Animals↗
PubMed2002

1-O-Alkylglycerol vesicles (Algosomes): their formation and characterization.

1-O-alkylglycerols (ALKG) have exhibited several biological activities and a prominent effect on blood-brain barrier permeability. They have markedly improved brain uptake of cancerostatic agents. Since ALKG are amphiphilic, we explored their tendency to assemble into bilayer vesicles, which can be applied as carriers for drugs. Vesicles (Algosomes) were formed by film hydration method using ALKG (tetra-, penta-, hexa-, hepta-, octa- or nona-decylglycerols) in combination with cholesterol (CHOL) and dicetyl phosphate (DCP) (1-O-alkylglycerol:CHOL:DCP in 45:45:10 molar ratio). On microscopic examination, the algosomes were found to be conspicuously spherical and the dispersion was a mixture of multi-lamellar and small-unilamellar vesicles. Phase transition temperatures of 1-O-hexadecylglycerol (HXDG) and CHOL mixtures were tested by differential scanning calorimetry (DSC). The changes in phase transition temperatures indicate the vesicle forming tendency of ALKG in presence of CHOL. Alkyl chain length dependent variations in vesicle size, zeta-potential (ZP) and capture volume (CV) could not be observed. Vesicles of 1-O-tetradecylglycerol (TTDG) showed improvement in CV with increase in CHOL content from 15 to 55 mol%. However the vesicle size decreased. On challenging algosomes with hypertonic salt solution [potassium iodide (KI) in water], vesicle size decreased and thus algosomes were found to be osmotically sensitive. Algosome dispersions on addition of higher concentrations of KI (40-100 mM) brought about increases in vesicle size and at concentrations 60 mM and above showed aggregation. All vesicular dispersions were stable for only a few days.

Biological Transport↗
PubMed2001

Pharmacokinetics of zidovudine following intravenous bolus administration of a novel niosome preparation devoid of cholesterol.

A novel niosome preparation composed of nonionic surfactants, polyglyceryl-3-diisostearate and polysorbate-80, bilayers stabilized by myristyl alcohol instead of cholesterol was developed. Polyglyceryl-3-diisostearate, myristyl alcohol and polysorbate-80 were in 1:2:1 molar ratio in which 85% zidovudine (3'-azido-3'-deoxythymidine, azidothymidine, AZT, CAS 30516-87-1) was found to be encapsulated in aqueous core. Pharmacokinetic and tissue distribution studies were conducted on this niosome preparation using rabbits and albino rats, respectively, as animal models. AZT levels in rabbit serum were higher following application of niosomal AZT than with AZT solution. Such levels were maintained for prolonged time. T1/2 increased, clearance became slow and as a result AUC and AUMC increased and consequently MRT increased following niosomal AZT treatment. Tissue distribution studies on albino rats also confirmed higher concentration and slower decline of serum levels of AZT due to niosomal AZT. In addition niosomal AZT escaped uptake by reticuloendothelial tissues (liver, spleen, and kidney). Invitro release of AZT from niosomes was slow, about 20% releasing in 18 h. The prolonged AZT levels in rabbit serum following the treatment with niosomal AZT appear to be due to the combined effect of slow invivo release and avoidance of extravascular distribution. Though this preparation seems to maintain AZT levels in serum for a prolonged time, its therapeutic efficacy cannot be claimed as the present method estimates total AZT in the preparation and not free AZT. Further no specific experiments were conducted to substantiate its therapeutic effect.

Animals↗
PubMed2001

Extreme lateral approach to ventral and ventrolaterally situated lesions of the lower brainstem and upper cervical cord.

Lesions situated ventrally and ventrolaterally to the lower brainstem and upper cervical spinal cord test the skills of neurosurgeons. We present our experience with eight such patients who underwent the extreme lateral craniocervical approach. The pathologies encountered include three distal vertebral aneurysms, one prepontine epidermoid, one anterior foramen magnum meningioma, and three high cervical dumbbell neurofibromas. All lesions were treated effectively. Postoperatively, the patients improved significantly. Complications included transient lower cranial nerve paresis in three patients, meningitis in one patient, and a pseudomeningocele in two patients. All complications improved with therapy. We conclude that the extreme lateral approach offers excellent visualization and access with minimal neural retraction for treating these difficult lesions.

Journal Article↗
PubMed2000

Biliary lipid peroxidation products in gallbladder cancer: increased peroxidation or biliary stasis?

Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance liquid chromatography (HPLC) analysis was carried out in 30 bile samples obtained during laparotomy from patients with gallbladder cancer (n = 10), cholelithiasis (n = 10) and age- and sex-matched controls (n = 10). A significantly high concentration of HNE and lower concentration of biliary pH and electrolyte was observed in patients with carcinoma of the gallbladder compared with controls and patients with cholelithiasis. A significant correlation was also observed between biliary Na+ and K+ (r = 0.72), biliary Ca2+ and Na+ (r = 0.69) among controls. However, there was no correlation between HNE, electrolytes and pH among cancer patients. An increased concentration of biliary HNE and decreased concentration of electrolytes suggest biliary stasis rather then increased peroxidation in cancer patients.

Aldehydes↗
PubMed2000

Lack of pharmacokinetic interaction between sumatriptan and naproxen.

Sumatriptan is a 5HT1D agonist used in the treatment of migraine. Nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium channel-blocking antagonists are used in the prophylaxis of migraine. Hence, there is a need to investigate the interaction of these prophylactic drugs with sumatriptan. The interaction of sumatriptan with propranolol, flunarizine, pizotifen, and butorphanol were reported earlier. Naproxen is shown to be effective in prophylactic treatment of migraine. In this study, the authors have investigated the circadian rhythm effect of naproxen on the pharmacokinetics of sumatriptan at 1000 and 2200 hours. Twelve healthy volunteers were treated with 100 mg sumatriptan succinate either alone or along with 500 mg naproxen orally at either 1000 or 2200 hours in a randomized Latin square design with a washout period of 10 days. Serum samples were collected at predetermined time intervals and analyzed for unchanged sumatriptan by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by using model-independent methods. Naproxen had no statistically significant (p > 0.05) effect on any pharmacokinetic parameters of sumatriptan both at 1000 and 2200 hours treatment. The results of this study suggest that no alteration in the sumatriptan dosage will be necessary for migraine patients taking naproxen prophylactic therapy.

Adult↗
PubMed2000

Vertebral artery aneurysms.

Vertebral artery (VA) aneurysms are rare. We present our experience with three cases of VA aneurysms. Two aneurysms were located close to the origin of basilar artery while the third patient had a giant posterior inferior cerebellar artery aneurysm. These aneurysms were operated by the far lateral inferior suboccipital approach with good results.

Adolescent↗
PubMed1999

Pharmacokinetics of pentoxifylline after oral administration of a sustained release tablet at two different times of the day.

The pharmacokinetics of pentoxifylline (CAS-6493-05-6) was studied in healthy subjects by orally administering a 400 mg sustained release tablet (Trental) at two different times (10:00 or 22:00 h) of the day in a crossover design. Pentoxifylline concentrations in serum samples were estimated by using high performance liquid chromatography. The mean values of Cmax (326.38 +/- 39.77 vs 266.35 +/- 36.0 ng/ml, p < 0.01, n = 8), AUC0-t (2424 +/- 382 vs 2141 +/- 300 ng/ml/h, p < 0.05, n = 8) were significantly higher and Vss/f (16537 +/- 2869 vs 20136 +/- 5006 ml/kg), Vd/f (11807 +/- 2704 vs 15801 +/- 5960 ml/kg) were significantly (p < 0.05, n = 8) lower following morning (10:00 h) administration than in the night (22:00 h). These variations should be considered while designing sustained release dosage forms.

Adult↗
PubMed1999

Time dependent influence of diazepam on the pharmacokinetics of ibuprofen in man.

Circadian variation in the disease activity of rheumatoid arthritis has been established. Several nonsteroidal anti-inflammatory drugs have been studied for their chronokinetic behaviour. Time dependent influence of diazepam on the pharmacokinetics of diclofenac and naproxen has been reported. We report the time dependent influence of diazepam on the pharmacokinetics of ibuprofen in healthy subjects. Either ibuprofen or ibuprofen with diazepam was administered at 10.00 or 22.00 hours to eight healthy volunteers in a randomized crossover study. Serum ibuprofen levels were estimated by high performance liquid chromatography. There was a significant (p < 0.05) increase in mean elimination half life (2.39 +/- 0.42 to 3.59 +/- 0.35 h) following ibuprofen and diazepam administration compared to ibuprofen alone administered at 22.00 hours. The mean clearance of ibuprofen was therefore lowered from 62.7 +/- 8.9 to 41.7 +/- 2.6 ml/h/kg under the influence of diazepam during the night. Such a time dependent influence of diazepam on the pharmacokinetics of ibuprofen may be due to circadian variation in the pattern of protein production in the liver and/or competitive protein binding of the two drugs during the dark period.

Adult↗
PubMed1999

Time dependent pharmacokinetic interaction between phenylpropanolamine and chlorpheniramine maleate in human subjects.

The influence of time of administration on the serum levels of phenylpropanolamine when administered alone and in combination with chlorpheniramine maleate at two different times of a day was studied in healthy human volunteers in a randomized 4 x 4 Latin square crossover design with a washout period of ten days. Blood samples were collected at predetermined time intervals and serum samples were analysed for unchanged phenylpropanolamine using high performance liquid chromatography. The various pharmacokinetic parameters of phenylpropanolamine were calculated using model independent methods. There was a significant (P < 0.05) decrease in the rate of absorption of phenylpropanolamine following its administration in combination with chlorpheniramine maleate at 2200 hours. However, such a change was not observed for treatment at 1000 hours. The observed change may be due to the time dependent gastrointestinal effect of these drugs.

Chlorpheniramine↗
PubMed1998

Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs.

A putative estrogen receptor (pER) from mouse liver has been characterized. The heterodimer protein (81-84 kDa) consists of two covalently bound subunits (61-67 and 17-27 kDa) with following characteristics: sedimentation constant--4.9 S; IP--4.8; dissociation constant (Kd) for estradiol-17beta binding--0.7 nmol; binding sites--0.746 pmol/mg protein; relative binding affinity--estradiol-17beta--100, estrone--80 and estriol--30; specificity--does not bind, other natural steroids, synthetic estrogens, antiestrogens and bioflavonoids. Importantly, immunosuppressants, neuroleptic and carcinogens influence 3H-estradiol-17beta binding to pER. Interestingly, pER is a serine phosphatase and this may have relevancy to estrogen action in Alzheimer's disease. The polyclonal anti-pER antibody does not react with estrogen receptors (ER). ER antibody does not react with pER. Remarkably, anti-pER antibody reacts with calcineurin, a brain phosphatase and anti-calcineurin antibody reacts with pER. Immunohistochemical analyses showed that pER is undetectable in reproductive organs (except ovary). It is localized on the plasma or the nuclear membranes in some, in cytoplasm and/or nucleus in other cells of non-reproductive organs (skeletal, neural, vascular, hair and retina), and in tumors (mammary, endometrial and prostate cancers, and prostatic hyperplasia). The information presented justifies the proposition that pER may mediate the estrogenic actions in non-reproductive organs.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Circadian variations in the pharmacokinetics of pentoxifylline in man.

Optimization of therapy by chronopharmacology requires knowledge of rhythmic manifestations of disease activity and chronopharmacokinetic data of the drugs prescribed. Rhythmic functioning of the cardiovascular system in healthy and diseased subjects is manifested as circadian rhythms in blood pressure, cardiac output, heart rate, etc. The disposition of several cardiovascular drugs in man has been reported to be time-dependent. This study reports the effect of time of administration on the disposition of pentoxifylline. Twelve healthy volunteers were treated with 400 mg pentoxifylline orally at 0100, 0700, 1300 and 1900 h in a randomized crossover Latin-square design with a wash-out period of one week. Serum samples were analysed for unchanged pentoxifylline by HPLC. Pharmacokinetic parameters were calculated using a model-independent method. The mean values of various pharmacokinetic parameters after drug treatment at these times were, respectively: maximum plasma concentration (Cmax) 485+/-174, 646+/-175, 735+/-271 and 781+/-217 ng mL(-1); time to reach the maximum plasma concentration (Tmax) 1.90+/-0.39, 1.66+/-0.4, 1.31+/-0.41 and 1.32+/-0.44 h, mean residence time (MRT) 3.8+/-0.8, 2.9+/-0.5, 2.9+/-0.4 and 2.7+/-0.3 h, elimination half-life (t1/2) 1.93+/-0.86, 1.23+/-0.3, 1.39+/-0.3 and 1.23+/-0.18 h and volume of distribution at steady state (VdSS/f) 11991+/-4862, 8823+/-3484, 8275+/-2357 and 7063+/-1950 mL kg(-1). The mean Cmax value was significantly (P < 0.05) lower after drug administration at 0100 h than after other time-points whereas mean Tmax, MRT, VdSS/f and t1/2 values were significantly (P < 0.05) higher. These variations might be because of time-dependent changes in absorption and biliary excretion of pentoxifylline and should be borne in mind when designing sustained action dosage forms for the drug.

Adult↗
PubMed1998

Underutilization of the available services by the needy disabled leprosy patients in Government Leprosy Control Unit Puttoor, Chittoor district, Andhra Pradesh, South India.

This study was undertaken to find out the deformity profile, utilization of disability care services, factors associated with underutilization and the impact of educating leprosy patients with visible disabilities in self-care practices in the area covered by the LCU Chittoor. The disability prevalence rate in the area was 15 per 10,000 population. Training of the staff and teaching leprosy patients in self-care practices has shown a remarkable improvement in skin texture and ulcer situation of disabled leprosy patients.

Adolescent↗
PubMed1998

A comparative study of the cost and effectiveness of a modified system of MDT drug delivery system in a high endemic district (Nalagonda) of South India.

Fall in the case load (from 17,000 to 4,500), has changed the disease profile and introduction of fixed duration Therapy (FDT) has made management of leprosy cases rather easy in Nalgonda, a backward district in Andhra Pradesh. The system of drug delivery which was conceived for managing large case load, however, remains unchanged, thereby resulting not only in considerable wastage of resources but also in hampering other activities like case detection and patient care. This study was undertaken to develop and assess a modified system of drug delivery in terms of the cost and effectiveness, its overall effect on other activities in the programme and its acceptability by the field staff. Four Leprosy Control Units (LCUs) were selected and were randomly assigned either to study (Gudibanda, Suryapet) or control (Nalgonda, Bhuvanagiri) group. In the study group the modified drug delivery system replaced the existing system. The modified system consisted of the para medical worker being made responsible for patients at all the DDPs in his subcentre. The clinics were managed alternately by medical officers and non medical supervisors every month. In the control group each clinic was managed by medical officers every month and it covered two sub centers with each drug delivery point being assisted by a para medical worker. The study revealed that the modified system resulted in a saving of 130 man-days a month, a 30% saving in use of vehicle, a 30% saving in POL and improvement in case detection. There was no change in the clinic attendance and drug consumption compliance in the units where modified system was introduced.

Cost-Benefit Analysis↗
PubMed1998

Pharmacokinetics of a single dose of phenylpropanolamine following oral administration at two different times of the day.

Pharmacokinetics of a single oral dose of phenylpropanolamine (CAS 154-41-6) was investigated by administering 50 mg of the drug at 10.00 and 22.00 h to 8 healthy male volunteers in a crossover design with a wash-out period of 10 days. Serum samples were analysed for phenylpropanolamine using high performance liquid chromatography. Pharmacokinetic parameters were calculated using model independent method. A significant (p < 0.05) elevation in Cmax (227.45 versus 181.98 micrograms/l) was observed following the drug administration at 22.00 h as compared to 10.00 h. These variations may be due to circadian changes in gastric pH contributing to the time dependent changes in the absorption of the drug.

Administration, Oral↗
PubMed1997

Nerve growth factor stimulates in vitro invasive capacity of DU145 human prostatic cancer cells.

The prevalence of nerve growth factor (NGF) production in different human prostatic tumor cell lines (DU145, PC-3, LNCaP-FGC) was investigated using a specific enzyme-linked immunosorbent assay (ELISA) and compared to that of different human and rat prostatic tissue samples. In addition, the biological effects of NGF beta addition to the human prostatic cancer cell cultures were investigated. The ELISA technique showed the DU145 cell line to secrete measurable levels of NGF in the culture medium. When neurite-outgrowth determination in a pheochromocytoma cell line was used as a bioassay, the NGF synthesized by DU145 cells was confirmed to exhibit functional biological activity. No effect of exogenously added NGF could be established on tumor cell proliferation, on the basis of either colorimetric tetrazolium-based staining assay or bromodeoxyuridine incorporation. Also the expression of prostate specific acid phosphatase was not influenced by NGF addition. However, the in vitro invasive capacity (Matrigel) of DU145 cells was significantly increased by inclusion of 50 ng or 100 ng NGF beta/ml culture medium. In view of the clinically well-known perineural invasion of prostate cancer cells, the possible involvement of NGF as a (paracrine) factor in prostatic cancer metastatic behavior should be investigated further.

Alkaline Phosphatase↗
PubMed1997

Experience with cerebellopontine angle epidermoids.

OBJECTIVE: Cerebellopontine angle (CPA) epidermoids, although of benign nature, are of considerable neurosurgical interest because of their close proximity and adherence to the cranial nerves and the brain stem. We describe our experience and attempt to correlate the final outcomes with the extent of surgical removal. METHODS: Twenty-five consecutive patients with CPA epidermoids that were surgically treated were reviewed, and the final outcomes were assessed. RESULTS: Thirteen patients had trigeminal neuralgia. In 7 of the 13 patients, trigeminal neuralgia was the only presenting feature. The epidermoid was confined to the CPA in each of 6 patients, and in each of 18, it had varying degrees of supratentorial extension. One patient had a predominant supratentorial epidermoid with extension to the CPA. The lesions were totally excised in 12 patients. Near-total removal was accomplished in eight patients, and in the remaining five, partial removal was accomplished. Transient worsening of the cranial nerve functions occurred in 11 patients, probably as a result of aggressive dissection of the capsule from the cranial nerves. In 9 of the 11 patients, the cranial nerve functions improved by the time of discharge. All of the patients who had trigeminal neuralgia were relieved of their symptoms. Eighteen patients were followed up for a mean period of 42 months, and none had symptoms of recurrence. CONCLUSION: Aggressive surgical removal results in transient but significant cranial nerve dysfunction in the postoperative period. A conservative approach is indicated for patients in whom the capsule is adherent to the brain stem and the cranial nerves.

Adolescent↗