How to look for new drugs? What guidelines to use? Have we to continue investigations on plant and marine organisms? These questions arise frequently today. A pharmacological effect results from the addition of many effects at a molecular level, i.e. the interaction between a ligand and a receptor. As long as the chemical structure of this receptor remains unknown, studies of Nature's resources will yield the largest reservoir of new drugs. Nature provides our imagination with the pattern of novel biologically active molecules. Criteria classically used in the past to select plants for study were chemotaxonomy, ethnopharmacology or pharmacotaxonomy. Examples will be taken from personal experience, to illustrate work done according to the chemotaxonomical approach (Ochrosia and ellipticines), and the ethnopharmacological approach (antiinflammatory properties of Euphorbiaceae from New Caledonia). Taking into account that one of the major problems we have to face is the unsatisfactory classical pharmacological testing procedure, we have tried to set up a network grouping biologists and chemists. Among many results obtained, one concerns the use of the mammalian hypothalamo-pituitary system to screen effects of alkaloids extracted from Psychotria oleoides, a Rubiaceae collected in New Caledonia. Psycholeine exhibits an intriguing activity on GH release. Another result concerns the influence of a Labiatae extract on the adenylate cyclase system: 9 HODE extracted from Glechoma hederacea stimulates the basal level of enzyme activity in platelets, this activity being possibly involved in the folk uses claimed. Using the tubulin test to screen antimitotic activities of plant extracts, the biological activity of rhazinilam has been demonstrated as responsible for the antitubulin activity of a Malaysian plant, Kopsia singapurensis.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH terms: Animals; Drug Evaluation, Preclinical; Humans; Medicine, Traditional
Thyroid hormones mediate the biological activities of almost all organ systems in the body. Patients with a deficiency of these hormones may present with a wide spectrum of clinical symptomatology. This report is of an infant who presented with chronic anaemia which was found to be secondary to hypothyroidism associated with a hypoplastic lingual thyroid gland. Physicians need to be alert to the varied manifestations of hypothyroidism so as to avoid delay in diagnosis and treatment.
Estimation of oligosaccharidases in the jejunal mucosa is useful in the diagnosis and evaluation of primary and secondary oligosaccharide intolerance. Until recently these enzymes have been estimated by the method of Dahlgvist.4While the method is accurate and reliable it is tedious and cumbersome. We describe here a semi quantitative method, using the glucose analyser. (Copied from article).
A prospective study of 92 children with poisoning admitted to University Hospital, Kuala Lumpur is reported. Majority of the affected children were below 3 years of age and belonged to low income families. Household items, especially kerosene, and medications were most often implicated. All children recovered completely. Preventive strategies are discussed.
The stools of 97 children with acute gastroenteritis, attending a private paediatric clinic, were studied for infectious agents. Putative pathogenic microorganisms were identified in 47 cases (48.5%). Food poisoning Salmonella was the most common bacteria detected, 25 cases (25.8%). Rotavirus was present in 9 cases (9.2%). Interview of the parents and care-persons revealed a general lack of knowledge in the proper cleaning and sterilisation of milk bottles, rubber teats and pacifiers. In 44 households there were at least one animal kept and there were positive bacterial isolates from 47% of such households. However, positive isolates were found in only 26% of households with no kept animals. The implications of these findings are discussed. (Copied from article).
To verify the actual immunisation coverage in Kuala Lumpur, City Hall Health Department and the Malaysian Paediatric Association (NGO ) carried out a survey. The survey revealed that the immunisation coverage determined at the child's first birthday for BCG was 95%, DPT 3 94%, OPV 3 94%, and measles = 27% (59% at 2 years). These figures correspond closer to City Hall's estimated coverage rather than the rates projected by the Ministry of Health. The main reasons for immunisation failure were, child ill 31.8% (not brought = 20.1%, brought but not given vaccine 11.7%), lack of information 28.6%, lack of motivation 9.1%, mother too busy 9.1%. Measles immunisation coverage at 1 year was low because of wrong information on schedules. Tetanus toxoid immunisation coverage of pregnant women was low. Only 27% of children were protected against neonatal tetanus although 97% of pregnant women received antenatal care and 50% had attended other health facilities as well during pregnancy. Private medical practitioners were responsible for more than 40% of all immunisations but were not submitting returns to the Health Department. Recommendations to improve immunisation coverage include education and motivation of the public and also doctors and health personnel on prevention of missed opportunities, contraindictions to immunisation and correct schedules. (Copied from article).
MeSH terms: Female; Health Facilities; Health Personnel; Humans; Immunization; Measles; Mothers; Motivation; Mycobacterium bovis; Pregnancy; Surveys and Questionnaires; Tetanus; Tetanus Toxoid; Vaccination
Human Herpesvirus-6 (HHV-6) infections are ubiquitous in human populations with an antibody prevalence of 30-85 percent in normal adults. The virus in vivo infects T-lympho-cytes, at various stages of differentiation and is cytopathic to host cell during productive infection. In culture the virus is pleiotropic for several established cell lines including T and B lymphocytes, macrophages and neural cells. Primary viral infection occurs mostly in early childhood. The saliva is the primary source of infection. The infection remains clinically silent in majority but it establishes a lifelong latent presence. However, in about 30 percent of infants, probably a varient HHV-6, causes exanthem subitum (roseola infantum). If the primary infection of HHV-6 is delayed until adolescence it is accompanied by clinical manifestation of an Epstein-Barr virus like infectious mononucleosis in some individuals. Depressed host immune functions may reactivate the latent HHV-6 infection and further aggravation of the primary disease. Since the virus is cytopathic to the host cell the presence of HHV-6 in AIDS patients and other lympholiferative disorders may increase the severity and pathogenicity of the primary disease. Antibodies to the HHV-6 are enhanced in autoimmune disorders, chronic fatigue syndrome, progressive lymphoroliferative disorders and organ transplant patients on immunosuppressive drugs therapy. While considerable basic immunovirological information has been obtained in the last 4 years, large gaps in knowledge still exist on the biologic interaction of HHV-6 with the host.
The total serum IgE levels in infants and children was quantitated by the radioimmunoassay technique. The serum levels increased from about 300 IUlml in the 2-3 month old infants to about 8000 1U/m1 in the 10-year-old children who were probably infected with intestinal helminths. The total serum IgE levels in infants with cow's milk protein-sensitive entero-pathy were similar in level to those in normal infants. Infants and children with acute gastroenteritis, giardia infection and malnutrition had elevated levels of serum IgE levels. The high serum I gE levels noted in Malaysian children are probably indicative of the pattern in the tropics. (Copied from article).
Components of the kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable agents as new analgesic drugs. Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel anti-rheumatic or anti-inflammatory drugs.
1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
A case of primary hepatocellular carcinoma (PHC) developing in a 10 year old boy who contracted Hepatitis B virus (HBV) infection in the course of maintenance phase chemotherapy for acute lymphoblastic leukemia was seen at University Hospital, Kuala Lumpur. This case is of interest in that it (1) supports an etiological relationship between HBV infection and PHC, (2) manifested a distinctly short malignant transformation time, and (3) draws attention to the possible contributory role of chemotherapy in increasing the risk of developing PHC.
New, detailed measurements have been made of the photon spectrum of the radionuclide 241Am. Observations, recorded for a 95% confidence level over local background, provide affirmation of a number of lines previously considered to be of equivocal existence. A number of hitherto unreported emissions are similarly observed. Peak areas, expressed as a percentage of that for the 59.54 keV emission, have been ascribed to all lines of the detailed spectrum. This leads to an estimated increase in the value of exposure calculated from the measured fluence spectrum, relative to that from the 59.54 keV line, of (3.1 +/- 0.8)%, taking into account all emissions beyond the predominating 59.54 keV gamma-ray emission.
Sixty cases with uterine leiomyomata in pregnancy are presented. The incidence was 1 in 1033 deliveries. The median age of the patients was 33.4 years. The majority were primigravidae (60%). A significant number of patients gave a history of infertility (43%) and spontaneous abortions (25%). The commonest antenatal complication was malpresentation and in all these patients the myomata were larger than 6 cm. Typical features of red degeneration occurred in 10% of cases. The cesarean section rate was 73%, the commonest indication being obstructed labor. Severe hemorrhage was encountered at cesarean section in 10 patients, 3 of whom needed hysterectomy. There were no perinatal deaths.
1. An extract prepared from the tentacle of the jellyfish (CE), Catostylus mosaicus exhibited haemolytic, oedema and haemorrhage-inducing activities. 2. Acetone treatment of the tentacle extract produced an acetone soluble extract (AE) which showed an increase in specific haemolytic and haemorrhagic activities by 25- and 120-fold respectively; the minimum oedema dose was reduced by 30-fold. 3. The AE caused a rapid onset of oedema in the mouse foot pad. The effect was long-lasting, reaching a maximum in about 30 min after injection and sustained up to 4 hr. 4. Fractionation of the AE on Q-Sepharose gave 4 bound fractions which induced oedema and haemorrhage; however only 3 of the fractions exhibited haemolytic activity.
1. The hemorrhagic, procoagulant, anticoagulant, protease, arginine ester hydrolase, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, phospholipase A and L-amino acid oxidase activities of 50 venom samples from 20 taxa of rattlesnake (genera Crotalus and Sistrurus) were examined. 2. The results show that notwithstanding individual variations in the biological activities of Crotalus venoms and the wide ranges of certain biological activities observed, there are some common characteristics at the genus and species levels. 3. The differences in biological activities of the venoms compared can be used for differentiation of the species. Particularly useful for this purpose are the thrombin-like enzyme, protease, arginine ester hydrolase, hemorrhagic and phospholipase A activities and kaolin-cephalin clotting time measurements.
1. The biological properties of twelve samples of venoms from all four species of Dendroaspis (mamba) were investigated. 2. Dendroaspis venoms generally exhibited very low levels of protease, phosphodiesterase and alkaline phosphomonoesterase; low to moderately low level of 5'-nucleotidase and very high hyaluronidase activities, but were devoid of L-amino acid oxidase, phospholipase A, acetylcholinesterase and arginine ester hydrolase activities. The unusual feature in venom enzyme content can be used to distinguish Dendroaspis venoms from other snake venoms. 3. All Dendroaspis venoms did not exhibit hemorrhagic or procoagulant activity. Some Dendroaspis venoms, however, exhibited strong anticoagulant activity. The intravenous median lethal dose of the venoms ranged from 0.5 microgram/g mouse to 4.2 micrograms/g mouse. 4. Venom biological activities are not very useful for the differentiation of the Dendroaspis species. The four Dendroaspis venoms, however, can be differentiated by their venom SDS-polyacrylamide gel electrophoretic patterns.
Three years ago the Universiti Kebangsaan Malaysia medical school changed its curriculum from the traditional discipline based curriculum to the integrated organ-system approach. Once change was effected a process of 'refreezing' had to be initiated whereby new responses had to be reintegrated into the ongoing personality or emotional relationships of important people so that the change process will endure and become stable. During this refreezing process the faculty encountered several problems which could thwart further development of the new curricula if left unresolved. The nature of the problems seemed to indicate that curricular change involves more than just efforts at bettering the what and ways of student learning and assessment. A lot of energy was also spent on keeping things going, keeping people motivated, making sure the work was done (at least as well as it has in the past), looking for better ways to do things, weighing new solutions and to be alert to new problems. In ensuring the continuance of change it was important to ensure, from the outset the institutionalization of policies, programmes, procedures and practices for continuing reward, routinization, structural integration into the system, continuing evaluation and providing for continuing maintenance.
MeSH terms: Adaptation, Psychological; Computers; Curriculum*; Faculty, Medical; Humans; Malaysia; Programmed Instruction as Topic; Students, Medical; Time Factors
Due to the increasingly documented prevalence of diarrhoeal diseases in Malaysia, a number of water-related programmes have been implemented in an attempt to improve health status through the reduction of incidence of waterborne communicable diseases associated with poor public water supplies. The implicit assumption underlying these projects is that the enhancement of the physical infrastructure, and subsequent improvements in the quality of the water supply, will substantially reduce water-related disease. The present study questions this hypothesis and uses a socio-ecological model as a framework to assess risk factors associated with the increased probability of waterborne disease. Research is centred on Port Dickson, a district which typifies existing water and sanitation conditions in much of semi-rural Malaysia. Health services utilization data and a 268-household diarrhoeal morbidity survey were used to measure the burden of illness of waterborne disease within the district and to identify predictors of morbidity. It was concluded that although treatment facilities will reduce the health burden in the region, a number of behavioural and sanitation factors may be more important and could act to minimize the potential impacts of improved water quality.
MeSH terms: Adolescent; Adult; Child; Child, Preschool; Diarrhea/etiology; Diarrhea/epidemiology*; Ethnic Groups; Health Status*; Humans; Hygiene/standards; Infant; Infant, Newborn; Health Knowledge, Attitudes, Practice; Malaysia/epidemiology; Middle Aged; Risk Factors; Sanitation/standards; Water Supply/standards*; Models, Statistical*; Health Behavior*; Incidence; Prevalence
1. The protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, procoagulant, anticoagulant and hemorrhagic activities of ten samples of venoms from seven taxa of sea snakes were examined. 2. The results show that venoms of sea snakes of both subfamilies of Hydrophiinae and Laticaudinae are characterized by a very low level of enzymatic activities, except phospholipase A activity and, for some species, hyaluronidase activity. 3. Because of the low levels of enzymatic activities and the total lack of procoagulant and hemorrhagic activities, venom biological properties are not useful for the differentiation of species of sea snakes. Nevertheless, the unusually low levels of enzymatic activities of sea snake venoms may be used to distinguish sea snake venoms from other elapid or viperid venoms.
A study of 12 patients with clinically definite multiple sclerosis (CDMS) using high dose infusion CT showed overall abnormality of 75% with an average of 2.5 lesions per patient. 75% of the patients showed abnormality of the cerebrum, mostly asymptomatic. The main changes were ventricular dilatation and asymmetry, isolated or generalized cerebral atrophy, areas of low attenuation mainly in the deeper parts of the cerebrum and the peri-ventricular area. 25% of the patients showed changes in the brainstem and none was seen in the cerebellum. The abnormality was more florid in patients with clinically disseminated forms of the disease. The study demonstrated that asymptomatic cerebral involvement is common among Asian patients with MS and CT is a useful tool in the overall assessment and diagnosis of Asian MS patients.