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Biomedical subjects

V Navaratnam

Publications and source records attributed to V Navaratnam.

At least 37 records · Page 2Linked to original sources
PubMed1996

The positions of coronary arterial ostia.

The positions of the coronary arterial ostia were examined in the cadavers of 38 adults. All the ostia were related to the aorta and none to the pulmonary artery. The aortic valves in 37 specimens were normal and possessed three cusps, while one was bicuspid. In the normal specimens, the main right and left coronary ostia were confined to the anterior and left posterior aortic sinuses respectively, apart from one specimen in which the right ostium was related to the right posterior sinus. Six specimens had small accessory ostia, close to the main right ostium. The majority of ostia were situated on or immediately below the supravalvular ridge. Circumferentially, the ostia clustered near the maximum curvature of the sinus. In the single specimen where the aortic valve was bicuspid, both ostia lay more-or-less symmetrically in the sinus above an anterior cusp which showed evidence of formation from two components. The reasons for confinement of the coronary ostia two of the three aortic sinuses are not clear. Microscopic examination of serial sections through 22 human embryos of 5.0-17.5 mm CR length (Carnegie stages XIII-XIX) confirmed that the earliest vessels in the heart wall develop subepicardially near the apex at stage XV. The network extends centripetally and only at stage XVII could coronary arterial stems, communicating with the aortic lumen, be identified. The sequence suggests that confinement of the coronary ostia to the interior and left posterior sinuses probably occurs because these represent the most accessible contact points for the centripetally growing vascular plexus.

Adult↗
PubMed1996

Morphometric study of specific heart granules in the grey seal (Halichoerus grypus).

Specific heart granules in the grey seal, Halichoerus grypus, a marine mammal, were studied and compared with those in the Wistar rat by ultrastructural morphometry. There is extreme paucity of these granules in atrial cells of the seal, even in the region of the Golgi apparatus, compared with those in the rat. By numerical concentration, granules in the seal are 23 times fewer in number than in the rat. They are also fewer in number than in bats and hamsters for which data is available. The mean (+/-SEM) diameter of heart granules in the seal is significantly less (188 +/- 5.3 nm) than that of the rat (226 +/- 4.6 nm). These observations, the first in a marine mammal, are of interest in relation to the need for conservation of water and electrolytes in pennipids.

Animals↗
PubMed1996

A clinical trial with halofantrine on patients with falciparum malaria in Colombia.

A total of 120 semi-immune adult male malaria patients from an area of multidrug-resistant Plasmodium falciparum malaria were hospitalized for 42 days in Medellin, Colombia (an area of no malaria transmission), and treated with halofantrine in a double-blind, randomized, prospective clinical trial according to five different treatment schedules. Each patient was assigned to one of the following halofantrine schedules: I, one dose of 1000 mg; II, three doses of 500 mg; III, two doses of 500 mg; IV, three doses of 250 mg; and V, one dose of 750 mg. Best results (75% cure rate) were obtained with schedule II, although there was no statistically significant difference compared with the other schedules. A total of 46 patients experienced recrudescent malaria. Drug levels in plasma 72 hours after beginning treatment showed no statistically significant difference between relapsing and cured patients. Side-effects (mainly gastrointestinal) were uncommon and mild. Cardiotoxicity was studied by electrocardiogram. A mean prolongation of 28.5 ms (6.6 +/- 6.3% increase from baseline) was observed in the Q-Tc interval on day 1 of the trial.

Adolescent↗
PubMed1995

Determination of artemether and dihydroartemisinin in blood plasma by high-performance liquid chromatography for application in clinical pharmacological studies.

A selective reproducible high-performance liquid chromatographic assay for the simultaneous quantitative determination of the antimalarial compound artemether (ARM), dihydroartemisinin (DQHS) and artemisinin (QHS), as internal standard, is described. After extraction from plasma, ARM and DQHS were analysed using a Lichrocart/Lichrosphere 100 CN stainless-steel column and a mobile phase of acetonitrile-0.05 M acetic acid (15:85, v/v) adjusted to pH 5.0, and electrochemical detection in the reductive mode. The mean recovery of ARM and DQHS over a concentration range of 30-120 ng/ml was 81.6% and 93.4%, respectively. The within-day coefficients of variation were 0.89-7.01% for ARM and 3.45-8.11% for DQHS. The day-to-day coefficients of variation were 2.06-8.43% and 3.22-6.33%, respectively. The minimum detectable concentration for ARM and DQHS in plasma was 2.5 and 1.25 ng/ml for both compounds. The method was found to be suitable for use in clinical pharmacological studies.

Adult↗
PubMed1995

Packed-column supercritical fluid chromatography of artemisinin (qinghaosu) with electron-capture detection.

In this preliminary report, a supercritical fluid chromatographic method is described for the determination of artemisinin in whole blood. The chromatography is carried out on a 20 cm x 1 mm I.D. Deltabond cyano supercritical fluid chromatographic column with detection of the artemisinin via an electron-capture detector. The sample work-up uses a liquid-liquid extraction with hexane, giving a recovery of 82%. The current limit of detection using 1 ml of blood is 20 ng/ml. We speculate that the endoperoxide moiety accounts for the response to the electron-capture detector and thus provides a new approach by which this class of compounds may be analyzed.

Antimalarials↗
PubMed1995

Ultrastructural features of left ventricular myocytes in active and torpid hamsters compared with rats: a morphometric study.

Myocytes from the midmyocardium of the left ventricle of rats and hamsters were examined by transmission electron microscopy. The volume fraction of lipid droplets in such myocytes was about 6 times greater in the active hamster than in the rat, but it became progressively reduced during cold exposure and entry into hibernation to values similar to those of the rat. The volume fraction of the T-system as well as the surface density of its membranes were each found to be twice as large in hamster myocytes as in the rat but there was no difference in these parameters between control, cold-exposed and torpid hamsters. The surface density of the junctional sarcoplasmic reticulum coupled with elements of the T-system was greater in active hamsters when compared with those of the rat, and greater still in torpid hamsters. There was no significant difference in the surface density of free sarcoplasmic reticulum between control hamsters, cold-exposed hamsters and rats but it was almost doubled in torpid hamsters. It is proposed that these features represent inherent differences in the ultrastructure of the left ventricle between the rat and hamster that may facilitate entry into hibernation. Additionally, further structural modifications during entry into hibernation may be related to alterations in lipid metabolism and modifications of calcium handling.

Adaptation, Physiological↗
PubMed1995

Chemotherapeutic effect of CGI 18041 against subperiodic Brugia malayi infection in Presbytis cristata.

CGI 18041, an adduct of benzothiazol isothiocyanate N-methyl piperazine, was evaluated for its antifilarial properties in subperiodic Brugia malayi infected Presbytis cristata. Animals experimentally infected with 200-400 subperiodic Brugia malayi infective larvae, were matched according to microfilaria density, infective dose, and duration of infection. They were then randomly assigned to various treatment and control groups. The compound was suspended in 1% Tween 20 in distilled water, sonicated, and then fed to monkeys using a stomach tube. Control animals received an equivalent volume of drug diluent. CGI 18041 at a single oral dose of 50 mg/kg had complete adulticidal and microfilaricidal activities against subperiodic B. malayi in P. cristata. It was also extremely effective at a single dose of 25 mg/kg, the final geometric mean microfilaria count being 1.6% of initial level, and only 1.0% of the infective dose was recovered as live adult worms at autopsy 6 weeks post-treatment. In control animals, these were 226.9% and 5.56% respectively.

Administration, Oral↗
PubMed1994

Determination of the antifilarial drug UMF-078 and its metabolites UMF-060 and flubendazole in whole blood using high-performance liquid chromatography.

A rapid and selective high-performance liquid chromatographic (HPLC) method for the simultaneous determination of the antifilarial drug UMF-078 (I) and its metabolites UMF-060 (II) and flubendazole (III) is described. After a simple extraction from whole blood, the compounds were determined by HPLC using a C18 Inertsil ODS-2 reversed-phase column with methanol-0.05M ammonium acetate (pH 4.0) as the mobile phase and ultraviolet detection at 291 nm. The average recoveries of I, II and III over the concentration range 20-500 ng ml-1 were 69.9 +/- 4.7, 85.6 +/- 4.4 and 85.1 +/- 6.0%, respectively. The minimum detectable concentrations in whole blood for I, II and III were 10, 7 and 7 ng ml-1, respectively. This method was found to be suitable for pharmacokinetic studies.

Animals↗
PubMed1994

Determination of naltrexone dosage for narcotic agonist blockade in detoxified Asian addicts.

Thirty-eight, adult, male, detoxified, Malaysian opiate addicts participated in this double-blind clinical evaluation of naltrexone. Addicts from three ethnic groups: Chinese, Malays, and Indians received a weekly regimen of naltrexone (100 mg on Days 1 and 3, and 150 mg on Day 5). Subjects were randomly assigned to receive intravenous challenge with either 25 mg heroin or placebo 12, 24, 48, and 72 h after the third naltrexone dose. Physiological and subjective parameters were measured at each challenge interval. Results indicated that naltrexone was effective in blocking the physiological and psychological effects of heroin for at least 48 and 72 h, respectively, in detoxified Malaysian opiate addicts. The efficacy of naltrexone did not differ among the three ethnic groups evaluated in this study.

Adult↗
PubMed1993

Determination of a new antifilarial drug, UMF-058, and mebendazole in whole blood by high-performance liquid chromatography.

A rapid and selective high-performance liquid chromatographic assay for simultaneous quantitative determination of a new antifilarial drug (UMF-058, I) and mebendazole (MBZ) is described. After a simple extraction from whole blood, both compounds were analysed using a C18 Nova Pak reversed-phase column and a mobile phase of methanol-0.05 M ammonium dihydrogenphosphate (50:50, v/v) adjusted to pH 4.0, with ultraviolet detection at 291 nm. The average recoveries of I and MBZ over a concentration range of 25-250 ng/ml were 92.0 +/- 7.7 and 84.4 +/- 4.4%, respectively. The minimum detectable concentrations in whole blood for I and MBZ were 7 and 6 ng/ml, respectively. This method was found to be suitable for pharmacokinetic studies.

Animals↗
PubMed1993

Treatment of subperiodic Brugia malayi infection with a single dose of ivermectin.

A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis.

Administration, Oral↗
PubMed1993

Recent advances in the chemotherapy of lymphatic filariasis.

Lymphatic filariasis is the most widespread of human filarial infections, a group of vector-borne infestations. After the discovery of diethylcarbamazine (DEC), little advance was made in the development of new chemotherapeutic agents for the treatment of lymphatic filariasis until 1985. Since then, several new initiatives have occurred as the result of a global effort by the World Bank/UNDP/WHO Special Programme on Tropical Diseases and the Onchocerciasis Control Programme. Some of these global research initiatives are reviewed in this paper. Recent observations throw a new light on the rational use of DEC including its deployment as a medicated salt. Ivermectin, an established drug for the treatment of river-blindness is examined for its potential use in the treatment of lymphatic filariasis. Experimental results from two novel compounds out of several being developed by the WHO/OCP Macrofil project are considered in respect to their potential macrofilaricidal activity, particularly in relation to lymphatic filarial infections.

Benzimidazoles↗
PubMed1991

Organisation and reorganisation of blood vessels in embryonic development.

The initial establishment of blood vessels is genetically predetermined but it is subsequently supplemented by local and haemodynamic factors. The earliest embryonic vessels arise independently in the mesenchyme of the yolk sac wall, chorion and embryonic disc. The angioblasts aggregate as cords which canalise by a process which includes intracellular vacuolation. Subsequent extension of the network occurs by a combination of (1) in situ formation of new vessels, (2) sprouting and fusion of established neighbouring vessels and (3) invading angioblasts from other regions. As capillaries mature, a basement membrane is established containing collagen IV, laminin, nidogen/entactin, heparan sulphate proteoglycan and a variable amount of fibronectin. Early capillary basement membrane contains more fibronectin which promotes proliferative and migratory activity of endothelium. As vessels mature, the endothelium switches to laminin secretion which causes differentiation including cell attachment, junction formation and establishment of tubes while cell proliferation is suppressed.

Basement Membrane↗
PubMed1991

Experimental chemotherapy of lymphatic filariasis. A review.

An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Adjunctive drug use among opiate addicts.

In a study of 249 opiate (mainly heroin) addicts special attention was paid to adjunctive drug use. Generally, nicotine (cigarette smoking), alcohol and cannabis preceded the use of heroin, and continued to be used as adjunctive drugs after the establishment of heroin addiction. Nicotine was the most common substance used together with opiates. Alcohol and cannabis were used as adjunctive drugs in about two-thirds of the cases. In the late stages of heroin addiction, benzodiazepines were also used concomitantly with opiates. The most frequently reported reason for the use of adjunctive drugs was to intensify the effect of the opiate. Three-quarters or more of the addicts had used different adjunctive drugs to boost the euphoric feeling derived from the primary drug, i.e. heroin. Attempt at self-treatment of withdrawal symptoms was a less frequently reported reason for adjunctive drug use. The findings show that heroin addiction is the major problem. The use of adjunctive drugs, especially benzodiazepines, can be partly explained on economic grounds. They must be clearly distinguished from the primary drug of abuse, heroin. For policy-making decisions, it is important that the elimination of heroin abuse through effective prevention measures would ultimately wipe out the problem of adjunctive drug use, while reduction of the overall supply of heroin without reduction in actual demand might result in an increasing trend to adjunctive drug use.

Alcohol Drinking↗
PubMed1990

Opiate dependence--the role of benzodiazepines.

In a recent epidemiological study of 249 opiate addicts in the State of Penang, Malaysia, the use of benzodiazepines, its temporal relationship to opiate addiction and the reasons for use of benzodiazepines were examined. Just over a half of the opiate addicts indicated use of benzodiazepines in their lifetime. Use of 7 different benzodiazepines was reported, among them flunitrazepam most frequently. A substantial proportion had discontinued the use of benzodiazepines after initial experimentation. Just over a quarter had used them in the last 24 hours. Benzodiazepine use starts on average 3 to 6 years later than heroin use. The most common reason cited for benzodiazepine use was to enhance the feeling of 'high' from the opiates. These findings can be explained, at least partly, by economic factors. Reasons that could be qualified as attempts to autotherapy did not exceed 20%. None of the opiate addicts had reported isolated benzodiazepine use for fun and pleasure. From the time course of use as well as from the reasons given by the addicts, it is evident that benzodiazepines are not primary drugs of abuse. Comparing their figures from Malaysia with figures from Germany and England the authors cannot explain the preferred use of flunitrazepam by Malaysian addicts by the existence of special properties of this substance.

Adult↗
PubMed1990

Morphology of presumptive rapidly adapting receptors in the rat bronchus.

The present investigation was undertaken in rats to determine whether sensory nerves exist in apposition to the bronchial microvessels which may function as rapidly adapting receptors (RAR). The primary and secondary bronchi on both sides were removed and processed for light and electron microscopy. Nerves were frequently found in relation to venules external to the muscle coat of bronchi. They comprised myelinated axons which ended individually as non-myelinated convoluted terminals enclosed within a loose capsule of attenuated cells. Serial sections showed that these terminals were not related to ganglion cells. Cervical vagal section and injection of HRP-WGA into the nodose ganglion provided corroborative evidence of the sensory nature of these terminals. Vagal section caused degenerative changes in the encapsulated nerve terminals in the bronchial walls and horseradish peroxidase labelling was demonstrable in such terminals. Moreover, immunocytochemical studies demonstrated the presence of calcitonin gene regulated peptide and substance P in these structures. It is suggested that they comprise the RAR. Encapsulated nerve terminals were not found in the epithelial layer, in the submucous coat or in the muscularis of bronchi.

Animals↗