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Fulltext Major surgery in an osteosarcoma patient refusing blood transfusion: case report

Dhanoa A, Singh VA, Shanmugam R, Rajendram R

World J Surg Oncol, 2010;8:96.
PMID: 21059231 DOI: 10.1186/1477-7819-8-96

We describe an unusual case of osteosarcoma in a Jehovah's Witness patient who underwent chemotherapy and major surgery without the need for blood transfusion. This 16-year-old girl presented with osteosarcoma of the right proximal tibia requiring proximal tibia resection, followed by endoprosthesis replacement. She was successfully treated with neoadjuvant chemotherapy and surgery with the support of haematinics, granulocyte colony-stimulating factor, recombinant erythropoietin and intraoperative normovolaemic haemodilution. This case illustrates the importance of maintaining effective, open communication and exploring acceptable therapeutic alternative in the management of these patients, whilst still respecting their beliefs.

Matched MeSH terms: Blood Transfusion/psychology*; Blood Loss, Surgical*
Intake of repeatedly heated palm oil causes elevation in blood pressure with impaired vasorelaxation in rats

Leong XF, Najib MN, Das S, Mustafa MR, Jaarin K

Tohoku J Exp Med, 2009 Sep;219(1):71-8.
PMID: 19713687

Oxidization of dietary cooking oil increases the risk of cardiovascular diseases such as hypertension by increasing the formation oxidative oxygen radicals. The aim of study was to investigate the effects of repeatedly heated palm oil on blood pressure, plasma nitrites, and vascular reactivity. Nitrites were measured, as an indirect marker for nitric oxide production. Male Sprague-Dawley rats were divided into four groups: control group fed with basal diet and other three groups fortified with 15% weight/weight fresh palm oil (FPO), palm oil heated five times (5HPO) or palm oil heated ten times (10HPO) for 24 weeks. The oil was heated to 180 degrees C for 10 min. Blood pressure was measured at baseline and at intervals of four weeks for 24 weeks using non-invasive tail-cuff method. Following 24 weeks, the rats were sacrificed and thoracic aortas were dissected for measurement of vascular reactivity. Blood pressure was elevated significantly (p < 0.05) in 5HPO and 10HPO groups, with the 10HPO group showing higher values. Aortic rings from animals fed with heated oil showed diminished relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Acetylcholine and sodium nitroprusside cause endothelium-dependent and endothelium-independent relaxation, respectively. Relaxation responses remained unaltered in the FPO group, with the attenuated contractile response to phenylephrine, compared to control group. FPO increased plasma nitrites by 28%, whereas 5HPO and 10HPO reduced them by 25% and 33%, respectively. Intake of repeatedly heated palm oil causes an increase in blood pressure, which may be accounted for by the attenuated endothelium-dependent vasorelaxant response.

Matched MeSH terms: Blood Pressure/drug effects*; Nitric Oxide/blood
In vivo study of human Plasmodium knowlesi in Macaca fascicularis

Anderios F, Noorrain A, Vythilingam I

Exp Parasitol, 2010 Feb;124(2):181-9.
PMID: 19765587 DOI: 10.1016/j.exppara.2009.09.009

Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious to humans. In this study Macaca fascicularis was used as a model to understand the host response to P. knowlesi using parasitological and haematological parameters. Three M. fascicularis of either sex were experimentally infected with P. knowlesi erythrocytic parasites from humans. The pre-patent period for P. knowlesi infection in M. fascicularis ranged from seven to 14 days. The parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual stage and 88-264 parasites per microL of blood for sexual stage. Periodicity analysis adopted from microfilaria periodicity technique of asexual stage showed that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h. Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to display periodicity with a peak (24:00-06:00) that coincides with the peak biting activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late trophozoite. However, it may be distinguishable by observing the appliqué appearance of the cytoplasm and the chromatin lying inside the ring. Haematological analysis on macaques with knowlesi malaria showed clinical manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross examination of spleen and liver showed malaria pigments deposition in both organs.

Matched MeSH terms: Alkaline Phosphatase/blood; Aspartate Aminotransferases/blood; Bilirubin/blood
Detection of IgM antibodies against Legionella pneumophila serogroup 1 in Malaysian blood donors and patients with respiratory illnesses: evaluation of enzyme-linked immunosorbent assay and indirect immunofluorescence assay

Tay ST, Lakhbeer Singh HK, Ramasame SD, Vadivelu J

Jpn J Infect Dis, 2009 Sep;62(5):409-10.
PMID: 19762997
Matched MeSH terms: Antibodies, Bacterial/blood*; Blood Donors; Immunoglobulin M/blood*
High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1

Tan CS, Cardosa MJ

Arch Virol, 2007;152(6):1069-73.
PMID: 17318736

Human enterovirus 71 has emerged as an important pathogen of children in the Asia Pacific region, and it may be important to consider the development of a vaccine against this virus. Human cord serum was used as a source of neutralizing antibodies to determine whether the N- or C-terminal half of the VP1 capsid protein was more likely to harbour neutralizing determinants. Cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect ELISA against recombinant VP1 antigen as well as the N- and C-terminal portions of VP1 antigen. High-titred human neutralizing antibodies were significantly more reactive with the N-terminal half of VP1 than weak or negative sera. The N-terminal half of human enterovirus 71 is likely to have important neutralizing antibody determinants and should be investigated further in vaccine development efforts.

Matched MeSH terms: Antibodies, Viral/blood*; Fetal Blood/immunology
Fulltext Correlation between fasting plasma glucose, post prandial glucose and glycated haemoglobin and fructosamine

Rosediani M, Azidah AK, Mafauzy M

Med J Malaysia, 2006 Mar;61(1):67-71.
PMID: 16708736 MyJurnal

This study was done to determine the correlation between glucose monitoring by fasting blood glucose or 2 hours postprandial blood glucose with HbA1c and fructosamine in type 2 diabetic patients. A total of 82 patients from the Primary Care Clinic were enrolled in the study. Fasting blood was drawn for fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and fructosamine. Two hours after a standard breakfast, blood was again drawn for prandial plasma glucose (PPG). Both PPG and FPG significantly correlated with both HbA1c and fructosamine but PPG showed better correlation to HbA1c than FPG (r= 0.604 vs.0.575) whereas that of FPG and PPG were equally correlated to fructosamine (r= 0.566 vs. 0.551). In predicting good glycaemic control (HbA1c < 7.0%), the sensitivity, specificity and positive predictive value of PPG were 75.0%, 80.6% and 82.5% whereas FPG were 81.8%, 58.3% and 70.6% respectively. These results show that PPG correlated better than FPG to HbA1c and both equally correlated to fructosamine levels. Thus, PPG predicted overall glycaemic control better than FPG. Compared to HbA1c, fructosamine correlated least well with mean glucose profiles. Hence, using HbAlc in monitoring overall glycaemic control is better than fructosamine.

Matched MeSH terms: Blood Glucose/metabolism*; Diabetes Mellitus, Type 2/blood
Fulltext A comparison between tocopherol and tocotrienol effects on gastric parameters in rats exposed to stress

Azlina MF, Nafeeza MI, Khalid BA

Asia Pac J Clin Nutr, 2005;14(4):358-65.
PMID: 16326642

Rats exposed to stress developed various changes in the gastrointestinal tract and hormones. The present study was designed to compare the impact of tocopherol and tocotrienol on changes that influence gastric and hormonal parameters important in maintaining gastric mucosal integrity in rats exposed to restrain stress. These include gastric acidity, gastric tissue content of parameters such as malondialdehyde, prostaglandin (PGE(2)), serum levels of gastrin and glucagon-like peptide-1 (GLP-1). Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups, a control group which received a normal rat diet (RC) and two treatment groups each receiving a vitamin deficient diet with oral supplementation of either tocopherol (TF) or tocotrienol (TT) at 60 mg/kg body weight. Blood samples were taken from half the number of rats (non-stressed group) after a treatment period of 28 days before they were killed. The remaining half was subjected to experimental restraint-stress, at 2 hours daily for 4 consecutive days (stressed groups), on the fourth day, blood samples were taken and the rats killed. The findings showed that the gastric acid concentration and serum gastrin level in stressed rats were significantly (P<0.05) reduced compared to the non-stressed rats in the control and TF groups. However, the gastric acidity and gastrin levels in the TT group were comparable in stressed and non-stressed rats. These findings suggest that tocotrienol is able to preserve the gastric acidity and serum gastrin level which are usually altered in stressed conditions. The PGE(2) content and the plasma GLP-1 level were, however, comparable in all stressed and non-stressed groups indicating that these parameters were not altered in stress and that supplementation with TF or TT had no effect on the gastric PGE2 content or the GLP-1 level. The malondialdehyde, an indicator of lipid peroxidation was higher from gastric tissues in the stressed groups compared to the non-stressed groups. These findings implicated that free radicals may play a role in the development of gastric injury in stress and supplementation with either TF or TT was able to reduce the lipid peroxidation levels compared to the control rats. We conclude that both tocopherol and tocotrienol are comparable in their gastro-protective ability against damage by free radicals generated in stress conditions, but only tocotrienol has the ability to block the stress-induced changes in the gastric acidity and gastrin level.

Matched MeSH terms: Gastrins/blood*; Stomach Diseases/blood; Glucagon-Like Peptide 1/blood
Fulltext A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid

Warrener L, Slibinskas R, Chua KB, Nigatu W, Brown KE, Sasnauskas K, et al.

Bull World Health Organ, 2011 Sep 01;89(9):675-82.
PMID: 21897488 DOI: 10.2471/BLT.11.088427

OBJECTIVE: To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips.
METHODS: The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips.
FINDINGS: With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20-25 °C.
CONCLUSION: The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation.

Matched MeSH terms: Antibodies, Viral/blood*; Immunoglobulin M/blood*; Nucleocapsid/blood
Fulltext Massive hemothorax following administration of intrapleural streptokinase

Chai FY, Kuan YC

Ann Thorac Med, 2011 Jul;6(3):149-51.
PMID: 21760848 DOI: 10.4103/1817-1737.82451

The administration of intrapleural streptokinase (IPSK) is widely practiced in the management of loculated empyema thoracis. To our knowledge, there have been only 4 cases of hemorrhagic complications attributed to the administration of IPSK reported in the literature. In this article, we report a case of a 17-year-old girl who received IPSK and developed shock, anemia, coagulopathy and massive hemothorax. Our discussion focuses on the hemorrhagic complication of chest tube insertion and the role of IPSK in blood clot lysis and inhibition of local hemostasis.

Matched MeSH terms: Blood Coagulation Disorders
Self-reported level of and factors influencing the compliance to desferrioxamine therapy in multitransfused thalassaemias

Lee WS, Toh TH, Chai PF, Soo TL

J Paediatr Child Health, 2011 Aug;47(8):535-40.
PMID: 21392144 DOI: 10.1111/j.1440-1754.2011.02017.x

To analyse the self-reported degree of and factors influencing the compliance to desferrioxamine (DFO) therapy in children with transfusion-dependent thalassaemia major in Malaysia.

Matched MeSH terms: Blood Transfusion; Ferritins/blood; Thalassemia/blood
Fulltext Low-density lipoprotein cholesterol goal attainment among Malaysian dyslipidemic patients

Al-Khateeb A, Mohamed MS, Imran K, Ibrahim S, Zilfalill BA, Yusof Z

Southeast Asian J Trop Med Public Health, 2011 Mar;42(2):388-94.
PMID: 21710862

The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.

Matched MeSH terms: Coronary Disease/blood*; Cholesterol, LDL/blood*; Dyslipidemias/blood
Fulltext Seroepidemiology of toxoplasmosis in renal patients

Nissapatorn V, Leong TH, Lee R, Init-Ithoi, Ibrahim J, Yen TS

Southeast Asian J Trop Med Public Health, 2011 Mar;42(2):237-47.
PMID: 21710842

Toxoplasmosis is an important parasitic disease in immunosuppressed patients. This prospective study was conducted to determine the seroprevalence, associated risk factors and the incidence of clinically confirmed toxoplasmosis among renal patients at the University of Malaya Medical Center, Kuala Lumpur, Malaysia. We interviewed 247 renal patients, each of whom answered an epidemiological questionnaire, and collected blood samples for measurement of anti-Toxoplasma IgG and IgM antibodies by ELISA. Overall seroprevalence of latent toxoplasmosis was observed in 126 (51%) renal patients. Race (Malays), marital status (married) and primary level of education, were all factors associated with a greater chance of Toxoplasma infection. A case of clinically confirned toxoplasmosis was diagnosed in a renal transplant recipient as a result of immunosuppression. Based on the findings obtained, this preliminary study shows a high prevalence of latent toxoplasmosis in renal patients. Risk factors may have significantly contributed to Toxoplasma acquisition in these patients. We recommend further studies be carried out to monitor for trends in toxoplasmosis among immunosuppressed patients.

Matched MeSH terms: Antibodies/blood; Blood Transfusion/adverse effects
Combined use of wild-type HBV precore and high serum iron marker as a potential tool for the prediction of cirrhosis in chronic hepatitis B infection

Chook JB, Ngeow YF, Yap SF, Tan TC, Mohamed R

J Med Virol, 2011 Apr;83(4):594-601.
PMID: 21328372 DOI: 10.1002/jmv.22016

Hepatitis B virus (HBV) and high liver iron deposits have both been associated with the development of cirrhosis. Among HBV factors, genotype and mutations in the basal core promoter (BCP) and precore regions have been most frequently studied but the evidence for a positive association with cirrhosis has been inconsistent. In this study, sera from persons with chronic HBV infection with and without cirrhosis were used for whole HBV genome analysis and for the estimation of serum iron marker (serum iron or ferritin) levels. Single codon analysis showed that the precore wild-type, TGG (nt 1,895-1,897), gave the highest accuracy (77.5%) for the identification of cirrhosis compared to other codons. When TGG was analyzed together with the precore start codon wild-type, ATG (nt 1,814-1,816), the accuracy was improved to 80.0% (odds ratio=35.29; 95% confidence interval=3.87-321.93; Phi=0.629; P<0.001). When the serum iron marker was included for analysis, it was clear that a combination of a precore wild-type and high serum iron marker gave a better accuracy (90.0%) (odds ratio=107.67; 95% confidence interval=10.21-1,135.59; Phi=0.804; P<0.001) for the identification of cirrhosis than either biomarker alone. It appeared that a combined use of both these biomarkers might help to predict the development of cirrhosis in a person with chronic HBV infection, but longitudinal studies are required to test this hypothesis.

Matched MeSH terms: Ferritins/blood*; Iron/blood*; Biomarkers/blood*
A transgressive brown rice mediates favourable glycaemic and insulin responses

Karupaiah T, Aik CK, Heen TC, Subramaniam S, Bhuiyan AR, Fasahat P, et al.

J Sci Food Agric, 2011 Aug 30;91(11):1951-6.
PMID: 21480266 DOI: 10.1002/jsfa.4395

BACKGROUND: We evaluated glycaemic response of a brown rice variant (BR) developed by cross-breeding. Subjects (n = 9) consumed 50 g carbohydrate equivalents of BR, white rice (WR) and the polished brown rice (PR) in comparison to 50 g glucose reference (GLU) in a cross-over design. Plasma glucose and insulin at 0, 15, 45, 60, 90, 120 and 180 min were measured and incremental area under the curve (IAUC) and indices for glucose (GI) and insulin (II) calculated.
RESULTS: BR compared to PR or WR produced the lowest postprandial glycaemia (GI: 51 vs 79 vs 86) and insulinaemia (II: 39 vs 63 vs 68) irrespective of amylose content (19 vs 23 vs 26.5%). Only BR was significantly different from GLU for both plasma glucose (P = 0.012) and insulin (P = 0.013) as well as IAUC(glu) (P = 0.045) and IAUC(ins) (P = 0.031). Glycaemic and insulinaemic responses correlated positively (r = 0.550, P < 0.001). Linear trends for IAUC(glu) and IAUC(ins) indicated a greater secretion of insulin tied in with a greater glycaemic response for WR (r(2) = 0.848), moderate for PR (r(2) = 0.302) and weakest for BR (r(2) = 0.122).
CONCLUSION: The brown rice variant had the lowest GI and II values but these advantages were lost with polishing.

Matched MeSH terms: Blood Glucose/analysis; Insulin/blood*
Fulltext First report of sylvatic DENV-2-associated dengue hemorrhagic fever in West Africa

Franco L, Palacios G, Martinez JA, Vázquez A, Savji N, De Ory F, et al.

PLoS Negl Trop Dis, 2011 Aug;5(8):e1251.
PMID: 21829739 DOI: 10.1371/journal.pntd.0001251

Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain.

Matched MeSH terms: Antibodies, Viral/blood; RNA, Viral/blood; Severe Dengue/blood
Effectiveness of medical nutrition treatment delivered by dietitians on glycaemic outcomes and lipid profiles of Arab, Omani patients with Type 2 diabetes

Al-Shookri A, Khor GL, Chan YM, Loke SC, Al-Maskari M

Diabet Med, 2012 Feb;29(2):236-44.
PMID: 21824187 DOI: 10.1111/j.1464-5491.2011.03405.x

In this randomized controlled trial we evaluated the effectiveness of medical nutritional therapy on Arab patients with Type 2 diabetes in Oman delivered by a dietitian.

Matched MeSH terms: Blood Glucose/metabolism; Diabetes Mellitus, Type 2/blood
Thickened carotid intima media thickness and carotid atherosclerosis among lupus nephritis patients: the role of traditional and lupus-specific factors

Sazliyana S, Mohd Shahrir MS, Kong NC, Tan HJ, Hamidon BB, Azmi MT

Int J Rheum Dis, 2011 Aug;14(3):267-75.
PMID: 21816023 DOI: 10.1111/j.1756-185X.2011.01638.x

AIM: The objectives of this study were to investigate the frequency of thickened carotid intima media thickness (CIMT) and atherosclerosis among lupus nephritis (LN) patients and to study their associated risk factors.
METHOD: In this cross-sectional study, carotid ultrasonography was performed on consecutive LN patients to determine CIMT and presence of carotid plaques. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex from the 'Carotid Atherosclerosis Progression Study'. The association between thickened CIMT with traditional cardiovascular risk factors and lupus characteristics were examined. A total of 83 patients with the mean age of 33.6 ± 10 years were recruited.
RESULTS: Fourteen patients (16.9%) had thickened CIMT and three (3.6%) had carotid plaques. On univariate analysis, traditional risk factors significantly associated with thickened CIMT (P < 0.05) were patient's current age, diabetes mellitus and waist circumference. Meanwhile, a lower serum C4 levels and higher serum C-reactive protein levels were the lupus-specific factors associated with thickened CIMT (P < 0.05, P < 0.05 and P < 0.01, respectively). In logistic regression analysis, the independent predictors of thickened CIMT were age of diagnosis, lower serum C4 levels and waist circumference (P < 0.05).
CONCLUSION: More lupus specific factors were independently associated with thickened CIMT, suggesting that a multi-targeted approach of treatment addressing both the lupus and traditional cardiovascular risks are very important. Larger prospective studies of these special risk factors are indicated.

Matched MeSH terms: Carotid Artery Diseases/blood; Lupus Nephritis/blood; Atherosclerosis/blood
Fulltext Familial aggregation and determinants of post challenge blood glucose in four ethnic populations

Lim TO, Rugayah B, Maimunah AH

Med J Malaysia, 2004 Aug;59(3):357-71.
PMID: 15727382 MyJurnal

We determine the familial aggregation and determinants of post challenge blood glucose (BG) in four ethnic populations. A national health survey was conducted in Malaysia in 1996. 18,372 subjects aged 30 years or older had post challenge BG measurements and another 846 subjects were pre-diagnosed to have diabetes on drug treatment. We imputed the BG of diagnosed diabetics by randomly selecting a value from the BG distribution of undiagnosed diabetics. Covariates of interest include ethnicity, gender, age, urban-rural residence, body mass index (BMI), physical activity, education, and household income. Ethnic and gender differences in mean BG persisted after adjustment for other covariates. Age and BMI were the only two factors with strong, positive and consistent effects on mean BG in all ethnic-sex groups. Family resemblance for BG as measured by intraclass correlation was small and homogenous across all ethnic groups and did not differ from resemblance in BG between spouses. In conclusion, BMI was the only consistent modifiable predictor of BG in all ethnic-sex groups. Environmental factors are probably more important than genetic factors as determinant of BG in the four ethnic populations studied.

Matched MeSH terms: Blood Glucose/metabolism*; Diabetes Mellitus, Type 2/blood
Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice

Moo KS, Radhakrishnan S, Teoh M, Narayanan P, Bukhari NI, Segarra I

Yao Xue Xue Bao, 2010 Jul;45(7):901-8.
PMID: 20931790

Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.

Matched MeSH terms: Antineoplastic Agents/blood; Piperazines/blood; Pyrimidines/blood
Adiponectin SNP45TG is associated with gestational diabetes mellitus

Low CF, Mohd Tohit ER, Chong PP, Idris F

Arch Gynecol Obstet, 2011 Jun;283(6):1255-60.
PMID: 20552210 DOI: 10.1007/s00404-010-1548-4

Diabetes and pregnancy can be associated in two ways: pregnancy that occurs in women who are already diabetic (diabetes of pre-gestational origin); and diabetes that occur in women who are already pregnant [gestational diabetes mellitus (GDM) (O'sullivan 1961)]. Patients with previous GDM history have higher risk of developing diabetes outside of pregnancy. Accumulating literature had suggested that adiponectin plays a role in the pathophysiology of this metabolic syndrome, and several of the common single nucleotide polymorphisms (SNP) in adiponectin gene have been identified in type 2 diabetes. Thus, one of the commonly found SNP was studied to determine its association with GDM.

Matched MeSH terms: Diabetes, Gestational/blood; Fructosamine/blood; Adiponectin/blood

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