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Echovirus 7 associated encephalomyelitis

Lum LC, Chua KB, McMinn PC, Goh AY, Muridan R, Sarji SA, et al.

J Clin Virol, 2002 Jan;23(3):153-60.
PMID: 11595594

Hand, foot, and mouth disease (HFMD) is endemic in Malaysia. In 1997, a large outbreak of enterovirus 71 (EV-71) associated HFMD resulted in 41 deaths due to severe left ventricular dysfunction and central nervous system infection with extensive damage to the medulla and pons. The clinical presentation in all these patients were rapid cardio-respiratory decompensation leading to cardiac arrest. Another large outbreak of HFMD with 55 fatal cases and a similar clinical picture was reported in Taiwan in 1998. In 2000, an outbreak of HFMD resulted in the deaths of three children who had rapid cardio-respiratory decompensation and one child who survived a central nervous system infection.

Matched MeSH terms: Encephalomyelitis/blood; Enterovirus Infections/blood
Homeostasis model assessment in a population with mixed ethnicity: the 1992 Singapore National Health Survey

Tai ES, Lim SC, Chew SK, Tan BY, Tan CE

Diabetes Res Clin Pract, 2000 Aug;49(2-3):159-68.
PMID: 10963828 DOI: 10.1016/s0168-8227(00)00152-2

We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.

Matched MeSH terms: Blood Glucose/metabolism; Blood Pressure
Nucleotide sequence of precore region of hepatitis B virus DNA in HBsAg-positive carriers in Malaysia

Ton SH, Iskandar K, Noriah R, Thanaletchimy N

Scand. J. Infect. Dis., 1996;28(6):543-8.
PMID: 9060053

As most published studies on precore mutants have been carried out on isolates from patients with liver diseases, and it is unclear whether HBsAg carriers with viraemia in the absence of HBeAg are also generally infected by such mutants, it was decided to sequence the precore region in some HBV-DNA isolated from HBsAg-positive carriers. Precore sequences of HBV-DNA from 43 HBsAg carriers in Malaysia were studied. Three HBV subtypes were identified according to the nucleotide sequence of the precore region. Most of the carriers were found to be infected by the subtype adr. Mutations were detected in the precore regions. The most common conserved mutation was a silent mutation involving conversion from T to C (CCT to CCC) at position 1858 at codon 15 (proline). It was found that 4/43 (9.3%) had a mutation at the penultimate codon where TGG was changed to TAG. All 4 isolates with the TAG mutation had nt T at position 1858. Of the 4 carriers who were infected by these mutant viruses, 2 were coinfected with the wild type, 1 was infected only by a variant with the mutation at position 1896, while another was infected by a variant with mutations at positions 1896 and 1899. Three of the 4 were anti-HBe positive while 1 was HBeAg positive. Alanine aminotransaminase activities in all 4 carriers were normal. This study therefore demonstrated that variants with stop codons at the penultimate codon could be found in asymptomatic carriers in Malaysia.

Matched MeSH terms: Hepatitis B e Antigens/blood; Hepatitis B Surface Antigens/blood
Dengue encephalitis: a true entity?

Lum LC, Lam SK, Choy YS, George R, Harun F

Am J Trop Med Hyg, 1996 Mar;54(3):256-9.
PMID: 8600761 DOI: 10.4269/ajtmh.1996.54.256

Involvement of the central nervous system in dengue fever and dengue hemorrhagic fever has always been thought to be secondary to vasculitis with resultant fluid extravasation, cerebral edema, hypoperfusion, hyponatremia, liver failure, and/or renal failure. Thus, the condition has been referred to as dengue encephalopathy. Encephalitis or direct involvement of the brain by the virus was thought to be unlikely. This paper reports on six children who were seen over a period of two years presenting on the second or third day of illness with dengue encephalitis. The diagnosis was based upon a clinical picture of encephalitis and confirmed by cerebrospinal fluid (CSF) microscopy and electroencephalography changes. All six cases were confirmed dengue infections. Dengue 3 virus was isolated from the CSF of four cases and in one case, dengue 2 was detected by the polymerase chain reaction in both the CSF and blood. In the sixth case, virologic evidence was negative but dengue immunoglobulin M was detected in the CSF and blood. Since the onset of encephalitis appears early in the course of illness coinciding with the viremic phase, we postulate that the virus crosses the blood-brain barrier and directly invades the brain causing encephalitis. This study provides strong evidence that dengue 2 and 3 viruses have neurovirulent properties and behave similarly to other members of the Flaviviridae.

Matched MeSH terms: Antibodies, Viral/blood; Immunoglobulin M/blood
High prevalence of thyroid function test abnormalities in chronic schizophrenia

Othman SS, Abdul Kadir K, Hassan J, Hong GK, Singh BB, Raman N

Aust N Z J Psychiatry, 1994 Dec;28(4):620-4.
PMID: 7794205

The thyroid status of 249 patients with chronic schizophrenia (males = 136, females = 113) with a median age of 36 years (range: 16 to 58 years) and a median duration of hospitalisation of 10 years (range: 1 to 30 years) was assessed. Thyroid antibodies (TAb) were found in 51 patients (20%). In female patients, 32 (28%) were TAb positive compared to 13% (n = 152, p = 0.01) in healthy female blood donors. In male patients, the prevalence of TAb was 14% compared to 7% (n = 449, p = 0.01) in healthy male blood donors. Of the 183 patients who had thyroid hormone measurements, 60% had normal test, 5% had elevated TSH and 17% had low TSH. The T4, FT41 and FT31 were significantly lower in those with low or high TSH (p < 0.001) compared to those with normal TSH. Of the 143 patients with normal TSH, 33 (23%) had low T3. In conclusion, there is a spectrum of thyroid function test abnormalities in chronic schizophrenia; this may be related to an abnormality in the central regulation of the hypothalamo-pituitary thyroid axis as well as at the peripheral level. However the association between chronic schizophrenia and the presence of thyroid antibodies, and the clinical relevance of these biochemical abnormalities, are still not clear.

Matched MeSH terms: Autoantibodies/blood; Thyroid Hormones/blood
Effect of ovariectomy and sex hormone replacement on glutathione and glutathione-related enzymes in rat hepatocarcinogenesis

Hambali Z, Ngah WZ, Wahid SA, Kadir KA

Pathology, 1995 Jan;27(1):30-5.
PMID: 7603748

The effects of ovariectomy and hormone replacement in control and carcinogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GRx) and histological evaluation. Hepatocarcinogenesis was induced by diethylnitrosamine and 2-acetylaminofluorene. In control rats not receiving carcinogen, ovariectomy significantly increased the GST and GRx activities. Replacement with either estrogen or progesterone reduced the GST activities to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx activities were brought to intact female values by replacement with estrogen or progesterone, either singly or in combination. Neither ovariectomy nor sex hormone/s replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcinogen showed lower GPx and GRx activities at 2 mths. However, replacement with either progesterone or combined estrogen and progesterone increased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatment were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activities (5 mths) in carcinogen treated rats were not influenced by ovariectomy and/or hormone/s replacement. The results from this study suggested that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement.

Matched MeSH terms: Glutathione/blood; Glutathione Transferase/blood
Serum IgA cross-reactivity between glycine-alanine repeat sequence of EBNA-1 and keratin or collagen in nasopharyngeal carcinoma

Mathew A, Cheng HM, Sam CK, Prasad U

Clin. Immunol. Immunopathol., 1994 May;71(2):164-8.
PMID: 7514112

Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.

Matched MeSH terms: Immunoglobulin A/blood; Nasopharyngeal Neoplasms/blood
Usefulness and limitations of thyrotropin measurements as a first-line test for follow-up of Graves' patients

Ng ML, Tan TT, Roslan BA, Rajna A, Khalid BA

Ann Acad Med Singap, 1993 Jul;22(4):569-72.
PMID: 7504901

We evaluated the usefulness of sensitive thyrotrophin hormone (TSH) measurements in determining the thyroid status in the follow-up of Graves' patients undergoing medical treatment with thionamides. Out of a total of 186 serum samples tested, TSH levels were suppressed in 123 (66.1%), normal in 32 (17.2%) and elevated in 31 (16.7%) cases. Total T4, or T3 or both were elevated only in 97 (74.8%) cases of TSH-suppressed patients, indicating that TSH is less discriminatory as a first-line test for patients under treatment due to the hypothalamic-pituitary lag period. No comparisons with free T4 or free T3 were done in this study. Both total T4 (120 +/- 28 nmol/l) and TBII (23 +/- 21%) levels were significantly greater (p < 0.02) in the euthyroid group with suppressed TSH. This may suggest that persistence of a thyrotoxic state may still be present.

Matched MeSH terms: Autoantibodies/blood; Thyrotropin/blood*
Gentamicin ototoxicity in continuous ambulatory peritoneal dialysis

Gendeh BS, Said H, Gibb AG, Aziz NS, Kong N, Zahir ZM

J Laryngol Otol, 1993 Aug;107(8):681-5.
PMID: 8409715 DOI: 10.1017/s0022215100124132

A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.

Matched MeSH terms: Gentamicins/blood; Kidney Failure, Chronic/blood
Fulltext Combined oral and parenteral iron chelation in beta thalassaemia major

Balveer K, Pyar K, Wonke B

Med J Malaysia, 2000 Dec;55(4):493-7.
PMID: 11221163

Thalassaemics in Malaysia are poorly chelated because desferrioxamine is too expensive and cumbersome for long term compliance. The efficacy and tolerability of the oral chelator deferiprone, and the effects of using a combination therapy in our patients were studied. Ten patients completed the study and the mean serum ferritin reduced from 7066.11 ug/L (2577-12,896 ug/L) to 3242.24 ug/L (955-6120 ug/L). The liver iron concentration did not show a significant drop (19.6 vs 18.2 mg/g dry weight) although 3 patients showed reductions ranging from 30-40%. Concomitant use of desferrioxamine increased the urinary excretion from a mean of 13.66 mg/day to 27.38 mg/day. Main side effects seen were nausea and rashes.

Matched MeSH terms: Ferritins/blood; beta-Thalassemia/blood
Seroprevalence of IgG antibodies against Chlamydia pneumoniae in Chinese, Malays and Asian Indians in Singapore

Koh WP, Taylor MB, Hughes K, Chew SK, Fong CW, Phoon MC, et al.

Int J Epidemiol, 2002 Oct;31(5):1001-7.
PMID: 12435775 DOI: 10.1093/ije/31.5.1001

BACKGROUND: Chlamydia pneumoniae, a bacterium that causes respiratory infections, is probably under-diagnosed. There is also interest in its possible role in the aetiology of coronary heart disease. This is the first population-based seroprevalence survey of C. pneumoniae infection in Singapore.

METHODS: A random sample of 1,068 people aged 18-69 years was selected from the participants of the Singapore National Health Survey conducted in 1998. Sera and data on certain clinical measurements and conditions had been collected. IgG antibodies for C. pneumoniae were detected using an indirect microimmunofluorescence test and positivity graded. Seropositivity was defined as IgG titre >/=1:16.

RESULTS: There were no statistically significant differences in the prevalence rates of seropositivity to C. pneumoniae for age group 18-69 years among the three ethnic groups, i.e. Chinese (males 76.7%, females 68.3%), Malays (males 75.4%, females 59.1%), and Asian Indians (males 74.6%, females 59.4%). The seropositivity rate for people aged 18-69 years in Singapore was 75.0% for males and 65.5% for females (difference of 9.5%, P < 0.001). In both genders combined, seropositivity increased from 46.5% in the age group 18-29 to reach a plateau of 78.9% in the age group 40-49, which remained stable to 60-69 years. There was no association of seropositivity with smoking, diabetes mellitus, hypertension or body mass index after adjustment for age and gender.

CONCLUSION: The high prevalence rates in our study population and the higher rate in males compared to females are consistent with studies from other parts of the world. No significant difference in prevalence rates was observed among Chinese, Malays and Indians. The pattern of rising and levelling off of seropositivity with age suggests that C. pneumoniae infection occurs early in life, and in older ages the high level of seropositivity is probably maintained by re-infections or chronic infections. Chlamydia pneumoniae infection was not found to be associated with the cardiovascular risk factors examined.

Matched MeSH terms: Antibodies, Bacterial/blood*; Immunoglobulin G/blood*
Clinical evaluation and serum concentration of zuclopenthixol acetate in psychotic Asian patients: a single-dose preliminary study

Tan CH, Low BL, Ng LL, Khoo YM, Lee HS

Ther Drug Monit, 1993 Apr;15(2):108-12.
PMID: 8099240

Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer trans(E)-clopenthixol were determined by high-performance liquid chromatography after intramuscular injection. All patients improved, with the BPRS being significantly reduced (p < 0.001) at 72 h after injection. Adverse effects were generally few. The mean +/- SEM serum zuclopenthixol concentrations at 24, 48, and 72 h were 19.9 +/- 2.8, 31.5 +/- 4.5, and 17.8 +/- 2.9 micrograms/L, respectively. trans(E)-Clopenthixol concentrations ranged from negligible to 39.5 micrograms/L. This study confirms that a single intramuscular injection of 50 mg is adequate for managing severely disturbed psychotic patients for the first 3 days. The serum zuclopenthixol concentrations attained in the Asian patients were higher than those reported in Caucasian psychiatric patients. In some patients, a considerable amount of zuclopenthixol had been transformed to trans(E)-clopenthixol.

Matched MeSH terms: Clopenthixol/blood; Antipsychotic Agents/blood*
Kidney activity increases in copper exposed goldfish (Carassius auratus auratus)

Moyson S, Liew HJ, Fazio A, Van Dooren N, Delcroix A, Faggio C, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2016 Dec;190:32-37.
PMID: 27521798 DOI: 10.1016/j.cbpc.2016.08.003

In the present study, the effect of copper was examined in the common goldfish (Carassius auratus auratus). Fish were fasted and exposed to either a high (0.84μM), a low (0.34μM) or a control copper concentration (0.05μM) for 1 and 7days. Swimming performance was not affected by either fasting or copper exposure. Food deprivation alone had no effect on ionoregulation, but low plasma osmolality levels and plasma Na(+) were noticed in fasted fish exposed to Cu for 7days. Both gill Na(+)/K(+)-ATPase and H(+)-ATPase activities were undisturbed, while both kidney ATPase activities were up-regulated when challenged with the high Cu levels. Up-regulated kidney ATPase activities likely acted as compensatory strategy to enhance Na(+) reabsorption. However, this up-regulation was not sufficient to restore Na(+) to control levels in the highest exposure group.

Matched MeSH terms: Goldfish/blood; Sodium/blood
Fulltext Iron status and dietary iron intake of adolescents from a rural community in Sabah, Malaysia

Foo LH, Khor GL, Tee ES, Prabakaran D

Asia Pac J Clin Nutr, 2004;13(1):48-55.
PMID: 15003914

Iron deficiency anaemia (IDA) is the most prevalent micronutrient deficiency in the world affecting the general health and wellbeing of millions. In Malaysia, moderately high prevalences of anaemia have been reported amongst infants, young children and women of childbearing age. Data is scant for the adolescents. This study was undertaken to assess the iron status and dietary intake of 165 adolescents, comprising 74 male and 91 female subjects, aged 12 to 19 years, from the rural communities in Tuaran District of Sabah, Malaysia. Convenience sampling was used for the selection of study subjects. Multiple iron status indicators namely, serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV) and haemoglobin (Hb) were determined for the study. The mean age of the subjects was 15.2 +/-2.1 years. While the majority of the subjects (77.6%) had normal body mass index (BMI) values, 17.6% were underweight and 4.8% overweight. About 35% to 40% of the subjects showed deficient values for haematocrit, serum ferritin, serum iron, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and transferrin saturation (TS), and 20% were anaemic (Hb <12 g/L). Using the multiple criteria of iron status indicators, the prevalence of iron depletion, iron deficiency and IDA in the male and female adolescents were 5.4% vs. 6.6%, 18.9% vs. 26.4% and 5.4% vs. 26.4%, respectively. Iron deficiency anaemia (85.0%) contributed largely to the prevalence of anaemia. The dietary iron intake of the adolescents was unsatisfactory, with approximately 98% of subjects failing to meet the Malaysian RDA level. Almost all the female subjects (91%) had dietary iron intake below two-thirds of the RDA level compared with a much smaller proportion for the male adolescents (68%). The prevalence of IDA in the present study population, especially in the female adolescents, appears to be a significant public health problem. Priority should therefore be given to the eradication of iron deficiency in adolescents from low-income areas by dietary modification and micronutrient supplementation amongst female adolescents.

Matched MeSH terms: Ferritins/blood; Iron/blood*
Recombinant VP9-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Banna virus (genus Seadornavirus)

Mohd Jaafar F, Attoui H, Gallian P, Isahak I, Wong KT, Cheong SK, et al.

J Virol Methods, 2004 Mar 01;116(1):55-61.
PMID: 14715307

Banna virus (BAV, genus Seadornavirus, family Reoviridae) is an arbovirus suspected to be responsible for encephalitis in humans. Two genotypes of this virus are distinguishable: A (Chinese isolate, BAV-Ch) and B (Indonesian isolate, BAV-In6969) which exhibit only 41% amino-acid identity in the sequence of their VP9. The VP7 to VP12 of BAV-Ch and VP9 of BAV-In6969 were expressed in bacteria using pGEX-4T-2 vector. VP9 was chosen to establish an ELISA for BAV, based mainly on two observations: (i). VP9 is a major protein in virus-infected cells and is a capsid protein (ii). among all the proteins expressed, VP9 was obtained in high amount and showed the highest immuno-reactivity to anti-BAV ascitic fluid. The VP9s ELISA was evaluated in three populations: French blood donors and two populations (blood donors and patients with a neurological syndrome) from Malaysia, representing the region where the virus was isolated in the past. The specificity of this ELISA was >98%. In mice injected with live BAV, the assay detected IgG-antibody to BAV infection 21 days post-injection, which was confirmed by Western blot using BAV-infected cells. The VP9 ELISA permits to determine the sero-status of a population without special safety precautions and without any requirements to propagate the BAV. This test should be a useful tool for epidemiological survey of BAV.

Matched MeSH terms: Antibodies, Viral/blood*; Immunoglobulin G/blood
Fulltext A golden hamster model for human acute Nipah virus infection

Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange M, Bernard A, et al.

Am J Pathol, 2003 Nov;163(5):2127-37.
PMID: 14578210 DOI: 10.1016/S0002-9440(10)63569-9

A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153-2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection.

Matched MeSH terms: Blood Vessels/pathology; Blood Vessels/virology
In vitro evaluation of actively targetable superparamagnetic nanoparticles to the folate receptor positive cancer cells

Nasiri R, Hamzehalipour Almaki J, Idris AB, Abdul Majid FA, Nasiri M, Salouti M, et al.

Mater Sci Eng C Mater Biol Appl, 2016 Dec 01;69:1147-58.
PMID: 27612812 DOI: 10.1016/j.msec.2016.07.076

Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.

Matched MeSH terms: Blood Cells/drug effects; Blood Cells/metabolism
Fulltext Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

Chua CL, Sam IC, Merits A, Chan YF

PLoS Negl Trop Dis, 2016 08;10(8):e0004960.
PMID: 27571254 DOI: 10.1371/journal.pntd.0004960

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.
CONCLUSION/SIGNIFICANCE: Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.

Matched MeSH terms: Antibodies, Viral/blood*; Antibodies, Neutralizing/blood
Fulltext Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response

Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.

Vaccine, 2016 09 14;34(40):4777-86.
PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028

Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.

Matched MeSH terms: Antibodies, Viral/blood; Antibodies, Neutralizing/blood
Prevalence of NIDDM and impaired glucose tolerance in aborigines and Malays in Malaysia and their relationship to sociodemographic, health, and nutritional factors

Ali O, Tan TT, Sakinah O, Khalid BA, Wu LL, Ng ML

Diabetes Care, 1993 Jan;16(1):68-75.
PMID: 8422835 DOI: 10.2337/diacare.16.1.68

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake.

RESEARCH DESIGN AND METHODS: The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects > or = 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT.

RESULTS: The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5-14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, > or = 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes.

CONCLUSIONS: Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.

Matched MeSH terms: Blood Glucose/analysis; Blood Glucose/metabolism

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