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Biomedical subjects

V Navaratnam

Publications and source records attributed to V Navaratnam.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

Adult↗
PubMed1989

Effects of expansion of blood volume and bilateral vagotomy on specific heart granules and release of atrial natriuretic peptide in the rat.

There was no statistically significant difference in basal concentrations of immunoreactive atrial natriuretic peptide (ANP), as assessed by radioimmunoassay, between right and left atrial muscle of control rats; similarly, stereological analysis showed no statistically significant difference in the fractional volume of myocytes occupied by specific heart granules, or in numerical density of granules, between right and left atria. Nevertheless, correlated radioimmunoassay and ultrastructural investigations showed that the major source of elevated plasma levels of ANP after expansion of blood volume was the right atrium. Substantial expansion of blood volume caused an increase in the proportion of peripherally located granules in myocytes of both atria, but reduction in the number of granules and in the concentration and total content of ANP occurred in the right atrium only. Bilateral cervical vagotomy also caused a statistically significant elevation of plasma ANP concentration, accompanied by a statistically significant reciprocal reduction in right atrial ANP content; no statistically significant change occurred in left atrial ANP. When blood volume was expanded after bilateral vagotomy, there was a further statistically significant increase in plasma ANP concentration; this was accompanied by further reduction in right atrial ANP and, moreover, the combined manoeuvre also elicited a statistically significant reduction of ANP in the left atrium. Ultrastructural studies confirmed that, under these conditions, myocytes in both atria showed a marked depletion of specific heart granules.

Animals↗
PubMed1989

Single dose kinetic study of the triple combination mefloquine/sulphadoxine/pyrimethamine (Fansimef) in healthy male volunteers.

A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/- s.d. for mefloquine (5.70 +/- 0.95 h), sulphadoxine (3.75 +/- 2.03 h) and pyrimethamine (3.30 +/- 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/- 98 h, 255 +/- 61 h and 114 +/- 42 h, respectively.

Adult↗
PubMed1989

Sequence of onset of different drug use among opiate addicts.

The temporal sequence of drug use should reveal which drugs are precursors to heroin and which drugs are used subsequent to the establishment of heroin addiction as adjunctive drugs. This temporal sequence was examined in an epidemiological study. Out of 249 opiate addicts interviewed in the area of Penang, Malaysia, this sequence of drugs could be obtained in 248 cases. The mean (median) age for first use of nicotine is 15.5 (15) years, alcohol 18.4 (18) years, cannabis 17.8 (17) years, heroin 21.8 (21) years, opium 22.8 (22) years, and benzodiazepines 25.8 (25) years. The age of first use of different drug types is presented in some detail. The patterns of sequence of drug use was analyzed for the five major and most frequently reported drugs, i.e. alcohol, cannabis, heroin, opium and benzodiazepines. Nicotine, used as first drug in almost all cases, was omitted in this analysis. A clear trend to multiple drug abuse emerges from this analysis; the biggest number of cases were users of 4 drugs (81 cases), followed by 3 drugs (59 cases) and 5 drugs (58 cases). Thus, nicotine, alcohol and cannabis are precursors of heroin addiction. Other adjunctive drugs become important only after heroin addiction. Among these substances, opium and benzodiazepines are numerically preponderant.

Adult↗
PubMed1989

Specific heart granules and natriuretic peptide in the developing myocardium of fetal and neonatal rats and hamsters.

The ontogenesis of specific heart granules and of the related natriuretic peptide activity in heart muscle was studied in fetal and neonatal rats and golden hamsters by ultrastructural analysis including immunogold labelling for ANP-28 and by radioimmunoassay. In both species, immunoreactive granules first appear in the myocardial sleeve of the embryonic heart tube during the looping stages which precede chamber formation and the peptide becomes detectable by radioimmunoassay two or three days later by which time the chambers are identifiable. Granule density and ANP concentration in the rat are higher than in the hamster at all stages of development. Almost all atrial myocytes express ANP in fetal hearts whereas, in the ventricular wall, cells containing immunoreactive granules are scattered. The density of granules in atrial myocytes increases during further stages of fetal and neonatal development, while it decreases markedly even in those ventricular myocytes which are immunoreactive. Changes in the ultrastructural appearance of ventricular SHG suggest that the mode of production of ANP changes in ventricular myocytes after birth but does not change in atrial cells. There is no correlation between the distribution of immunoreactive ventricular myocytes and that of the conducting system. In both species, the concentration of ANP in the atrial well is higher than ventricular levels from the outset and the disparity becomes exaggerated with development till, in six months old adult animals, the atrial to ventricular concentration ratio is about 3 x 10(3):1 in the rat and 1.5 x 10(3): 1 in the hamster. In the hamster, a distinct gradient of ANP concentration between the right and left atria is already established in the early fetal period and it becomes enhanced in the neonatal period. In the rat, however, a slight difference becomes discernible only after birth.

Animals↗
PubMed1989

An epidemiological assessment of drug dependence in Malaysia--a trend analysis.

Information from the national drug abuse monitoring system was analysed to determine the trends in extent and pattern of drug dependence in Malaysia over the period 1970 to 1986. The annual incidence and prevalence rates of reported drug dependents increased by many folds when compared to the early seventies. Generally, the profile of drug dependents identified has remained relatively stable throughout the years. A stable pattern of drug abuse was also noted over this period. Factors influencing the trend patterns are discussed, as well as the implications of these findings for policy purposes.

Adolescent↗
PubMed1989

Development and application of a system for monitoring drug abuse: the Malaysian experience.

Monitoring systems are useful epidemiological instruments for assessing the problem of drug abuse. The rapid growth of the drug dependence problem in Malaysia led to increased awareness of the need for a system for continuous monitoring of the situation. Preliminary work on the design of an appropriate monitoring system was initiated in 1976. A fully integrated national reporting system was established in 1978, linking all public services and agencies coming into contact with drug-dependent persons, including law enforcement agencies, drug abuse treatment and rehabilitation centres, and social and welfare institutions. The information system included a mechanism for systematic gathering, processing, analysing and presenting essential data on the prevention, control and management of drug abuse problems. It also included reporting on drug-related events, such as hospitalizations and arrests, as well as data on known drug-dependent persons and new cases of dependence. The system has been used for routine monitoring of the extent, trends, patterns and other characteristics of drug abuse problems in Malaysia, providing basic information for policy-making and programme planning. On the basis of data generated by the system, it was estimated that the prevalence rate of drug-dependent persons per 100,000 population increased from 84.3 in 1976 to 754.6 in 1986. It was estimated that there were 119,001 drug-dependent persons in Malaysia in 1986.

Drug and Narcotic Control↗
PubMed1988

Analysis of the apparent heterogeneity of specific heart granules in rat atrial myocytes; an ultrastructural study including immunocytochemistry.

Ultrastructural analysis of specific heart granules in the left atrial myocardium of the rat shows that the so-called A and B types are not different populations but represent varying planes of section through a uniform set of organelles. Histograms of the apparent diameters of granules in individual animals establish that they are unimodal and tilt series of micrographs through selected granules show that the appearances of A and B profiles are interchangeable during the tilting manoeuvre. Moreover, serial sections reveal that equatorial sections through a granule yield the typical appearance of A profiles while peripheral sections through the same granule yield a B type appearance. Immunocytochemical studies were conducted on acrylic resin-embedded specimens using antiserum raised to ANP-28 and visualized by labelling with protein-A gold. A type profiles are more heavily decorated with gold particles than B profiles, a feature which could be partially explained if there is a higher concentration of peptide at the centre of the granule core. Some peripherally sectioned caps of granules which project B type profiles do not exhibit immunoreactivity because their orientation within the thickness of the section prevents access of the antiserum but, after resectioning at right angles to the original plane, their ANP content is revealed by a second phase of immunogold labelling.

Animals↗
PubMed1988

Immunocytochemical localization of natriuretic peptide sequences in the human right auricle.

Samples of the right auricle from ten patients undergoing surgery were processed for the immunocytochemical localization of atrial natriuretic peptide sequences (ANP-28 and the 26-92, 26-55 and 56-92 segments of the prohormone) using commercially available antisera and labelled with protein-A gold. Single antigen and double antigen (ANP-28 and one other) detection procedures were employed. The results show that there is no correlation between the ultrastructural appearance of specific heart granules and the molecular form of their ANP content. All specific granule types contain the full range of prohormone sequences. D granules are few and appear to be recently budded from the Golgi apparatus, whereas A and B profiles comprise the majority of specific granules and are more widely distributed in the cytoplasm. In the Golgi elements, peptide immunoreactivity is principally associated with the membrane but a proportion lies within the of vesicles and becomes concentrated within the core of developing granules. The density of ANP-immunoreactivity is higher in A profiles than in the other types. Multivesicular bodies are not intrinsically immunoreactive for ANP, nor are the numerous synaptic nerve profiles which are present in atrial muscle. In two elderly patients the basal lamina of myocytes was heavily labelled for ANP.

Adult↗
PubMed1988

Relative bioavailability of the hydrochloride, sulphate and ethyl carbonate salts of quinine.

The hydrochloride, sulphate and ethylcarbonate salts of quinine were given in single oral doses (600 mg base equivalent) to nine healthy male subjects according to a cross-over design. No statistically significant differences were noted in the plasma drug concentration-time profiles although inter- and intra-subject variation in AUC, Cmax and tmax values was appreciable. The ethylcarbonate salt may be preferred for use in paediatric patients because of its neutral taste.

Administration, Oral↗
PubMed1988

The atrioventricular node of the golden hamster (Mesocricetus auratus): a light and electron microscopic study including immunocytochemistry.

The atrioventricular (AV) node of the golden hamster is situated unusually high in the interatrial septum when compared to other species such as the rat. 2 main cell types, characterized by electron-lucent or electron-dense cytoplasm respectively, are found in the node; although both types contain numerous myofilaments these are irregularly arranged and sarcomeric banding is poor. A third variety comparising transitional cells, with features intermediate between the main nodal cells and general atrial myocardial cells, are found at the periphery of the node. Similar electron-lucent and electron-dense cells are also found in the bundle and the mean diameter of bundle cells increases as one passes from the node to the bundle bifurcation. In the node, specific heart granules (SHG) identified by ANP-28 immunoreactivity are found only in transitional cells and even here they are very sparse, unlike general atrial myocytes in which they are plentiful. Numerous nerve varicosities are present throughout the node and bundle and 5-hydroxydopamine (5-OHDA) labelling demonstrates that most of them have features of either noradrenergic or cholinergic terminals; a few non-cholinergic, non-adrenergic varicosities are also present.

Animals↗
PubMed1988

Ultrastructure of the internodal myocardium in the rat.

Ultrastructural studies of the rat atrial myocardium reveal that the specialised myocardial cells can be distinguished from the usual atrial myocytes by their lack of specific atrial granules. On the basis of this distinction it has been shown that there is interposition of atrial myocardial tissue in the pathway between the two nodes and that there are no morphologically specialised internodal pathways. The atrial myocardial cells themselves exhibit variations in their content of cytoplasmic organelles such as myofibrils, T-tubules and sarcoplasmic reticulum but they all contain membrane-bound specific atrial granules.

Animals↗