Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population

Background Genetic predisposition has been suggested to play role in the pathogenesis of thyrotoxic hypokalaemic periodic paralysis (THPP). Objectives In this study, we assessed the differences of single‐nucleotide polymorphisms (SNP) allelic frequency between THPP patients and well‐characterized controls in order to find the susceptibility genetic variants related to THPP using microarray‐based assessments on pooled DNA. Methods Fifty cases of THPP and 50 male hyperthyroid patients without hypokalaemia as controls were recruited. Equal amounts of individual genomic DNA were pooled from each group. Estimated allele frequencies of SNPs were derived by averaging relative allele signal score obtained by Affymetrix GeneChip® Mapping 10K Arrays. Results Sixty‐nine loci that display robust allele frequency differences between THPP and controls were identified. SNP rs750841 (A > T) in intron 3 of the gamma‐aminobutyric acid (GABA) receptor α3 subunit (GABRA3) gene possessed the most significant difference in allele frequency (27% in THPP case and 5% in controls, P = 0·007). Actual allele frequencies obtained from genotyping in each individual were very similar to the estimated frequency from the pools (28% in THPP and 2% in controls, and P = 0·0002). Nearby DNA sequences of GABRA3 were sequenced and an additional two SNPs were found (A > C at exon 1 and G > T of rs12688128). Allele A of rs750841 and allele G of rs12688128 in intron 3 were predominantly found in THPP with significant genetic relative risk of 19 (P < 0·0002; 95%CI 2·4–151·6). Conclusions Whole‐genome scanning on pooled DNA provides an accurate, useful screening tool for elucidating genetic underpinnings of THPP. SNPs at intron 3 of GABRA3 are found to be associated with THPP.     

Reduced attenuation of bone resorption after oral glucose in type 2 diabetes

Objective  To investigate the effect of oral glucose on bone resorption and osteoprotegerin (OPG) in subjects with varying degrees of glucose tolerance.
Design and Patients  In a cross-sectional study, 163 postmenopausal women aged 50–88 years without previous history of diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were recruited. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and were then classified as having normal glucose tolerance (NGT), IFG, IGT or diabetes according to American Diabetes Association (ADA) criteria.
Measurements  Plasma glucose, serum insulin, C-terminal telopeptide of type I collagen (CTX-I) and OPG were measured.
Results  Fasting insulin levels increased progressively from subjects with NGT, IFG/IGT to diabetes. After adjusted for age and body mass index (BMI), there was no significant difference in fasting CTX-I and OPG levels across the various degrees of glucose tolerance. After oral glucose, there was a significant decrease in serum CTX-I and OPG ( P <  0·001) except for serum OPG in diabetic subjects. In addition, the percentages of change from baseline for both serum CTX-I and OPG were significantly less in diabetic subjects when compared to those in NGT subjects (–40·9% and 0·6% for diabetes and –50·2% and –10·6% for NGT, respectively).
Conclusions  Oral glucose intake causes suppression of serum CTX-I and OPG in postmenopausal women. The effect is attenuated in women with type 2 diabetes.     

Insulin and C-peptide levels, pancreatic beta cell function, and insulin resistance across glucose tolerance status in Thais

Impaired pancreatic beta cell function and insulin sensitivity are fundamental factors in the pathogenesis of type 2 diabetes; however, the predominant defect appears differ among ethnic groups. We conducted a cross-sectional study to evaluate the contribution of impaired beta cell function and insulin sensitivity at different stages of the deterioration of glucose tolerance in Thais. The study involved 420 urban Thais of both sexes, 43-84 years old. A 75-g oral glucose tolerance test was performed on all of the subjects. Indices of insulin resistance and beta cell function were calculated with the use of a homeostasis model assessment. The subjects were classified as having normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and IGT, or type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. There were no differences between groups with regard to gender and age. The percentage of obesity was significantly greatest in the diabetic group. Fasting serum insulin and C-peptide levels progressively increased from the NGT to the diabetic subjects. Serum C-peptide was more strongly associated with newly diagnosed diabetes than insulin, and was an independent factor associated with newly diagnosed diabetic subjects. The insulin resistance index progressively increased when the glucose tolerance stage changed from NGT through diabetic subjects. Beta cell function did not change significantly in any other group compared to the NGT group. An increase in fasting serum C-peptide may be a risk factor for type 2 diabetes. Obesity and insulin resistance are the predominant features in the deterioration of glucose tolerance in Thais.     

Repellent and adulticide efficacy of a combination containing 10% imidacloprid and 50% permethrin against <Emphasis Type="Italic">Aedes aegypti</Emphasis> mosquitoes on dogs

This study was conducted to assess the repellent and adulticide efficacy of the combination containing 10% imidacloprid and 50% permethrin against Aedes aegypti mosquitoes on dogs. Blood-feeding success rates of the mosquitoes that were exposed to the treated dogs were 4.9 and 4.4% on days 3 and 7 post the combination application (PCA), respectively, and blood-feeding success rates increased to 6.3, 12.8, and 24.5% on days 14, 21, and 28 PCA, respectively. Blood-feeding success rates between the mosquitoes that were exposed to the treated and untreated control dogs on days 3, 7, 14, and 21 PCA were significantly different. All mosquitoes that were exposed to the treated dogs on day 3 PCA died, and mortality rates decreased to 97.1, 77.8, 40.4, and 2.1% on days 7, 14, 21, and 28 PCA, respectively. Mortality rates between the mosquitoes that were exposed to the treated and untreated control dogs on days 3, 7, 14, and 21 PCA were significantly different. This study suggested that this combination can be used to repel and kill mosquitoes on dogs; however, the application of this insecticide combination on dogs needs to be repeated every 3–4 weeks.     

Detection of tumor necrosis factor-α and interleukin-6 in exhaled breath condensate of rats with pneumonia due to staphylococcal enterotoxin B

Exhaled breath condensate (EBC) may contain mediators of acute lung injury. The objectives were to determine if EBC could be collected in a mechanically ventilated rat, to measure tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the EBC after staphylococcal enterotoxin B administration (SEB) and to find out if the concentrations of TNF-α and IL-6 correlated with those in lung lavage. Four hours after SEB instillation, rats were placed on mechanical ventilation and EBC was collected over 90 minutes. Lung lavage was collected and white cell count was determined. TNF-α and IL-6 were measured in the EBC and lavage. EBC was available in a sufficient quantity (250-400 μL) for the measurement of cytokines. The rats that received SEB had an inflammatory response when compared to control rats as shown by an increase in white cell count. TNF-α and IL-6 were detected in the EBC. Concentration of TNF-α correlated with that in the lavage (r = .497, P = .021), whereas IL-6 did not. EBC can be collected in rats in sufficient quantities to study acute lung injury. TNF-α and IL-6 can be measured in the EBC. Correlation between TNF-α in the EBC and lavage was demonstrated in this rat model of lung injury.     

Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: Using the International Diabetes Federation criteria

Background. Since insulin resistance and compensatory hyperinsulinemia are the major causes of the metabolic syndrome (MS) and are also the main pathophysiology of polycystic ovary syndrome (PCOS), PCOS women are at risk of MS. The aim of the present cross-sectional study was to determine the prevalence of MS in Asian women with PCOS using the International Diabetes Federation (IDF) criteria and to define the risk factors.

Methods. One hundred and seventy women with PCOS were enrolled in the study from September 3, 2002 to June 14, 2005. A 75-g oral glucose tolerance test with plasma glucose and serum insulin levels was performed. Also, blood samples were examined for fasting triglycerides, high-density lipoprotein cholesterol and adiponectin levels.

Results. The mean (±standard deviation) age, body mass index (BMI) and waist-to-hip ratio were 28.8±5.9 years, 27.1 ± 7.0 kg/m² and 0.85±0.06, respectively. The prevalence of MS was 35.3%. Age, BMI, waist circumference and all metabolic parameters were higher in PCOS women with MS than in those without MS. MS prevalence increased with age, BMI and insulin resistance as determined by homeostasis model assessment (HOMA-IR), but not with adiponectin after BMI adjustment.

Conclusions. According to the IDF criteria, one-third of the PCOS women had MS. This study also showed that age, BMI and HOMA-IR are important risk factors for MS.     

IFN type I and type II independent enhancement of B cell TLR7 expression by natural killer cells

The PRR TLR7 plays a key role in the activation of autoantigen-reactive B cells. This response is increased markedly by IFN-α, produced by accessory cells, as a result of the up-regulation of TLR7. We report herein an alternative pathway by which TLR7 expression can be augmented. This finding was derived from continuation of ongoing studies to uncover interactions between NK and B cells. Here, we have compared gene expression profiles by microarray analysis of B cells before and after their interaction with purified NK cells. The most outstanding alteration of genes transcribed in B cells is a significant increase in the expression of many members of the ISG family, among which is TLR7. Further analysis revealed that the enhancement of TLR7 on B cells is not mediated via type I or type II IFN but by another cytokine, IL-28, a type III IFN, which acts in concert with contact-mediated interactions with NK cells. This increased expression allows B cells to respond more readily upon stimulation by its ligand and may increase in vivo responses to other TLR7 ligands, such as autoantigens, prior to or jointly with stimulation by other cytokines.     

Vector competence of Aedes aegypti (L.) and Culex quinquefasciatus (Say) for Dirofilaria immitis (Leidy)

This study was performed to examine the vector competence of Aedes aegypti and Culex quinquefasciatus for Dirofilaria immitis. Eleven individual experiments were conducted in this study. Nonthaburi and Udon Thani strains of Ae. aegypti were allowed to feed on infected dogs that had 5,750 and 4,600 microfilariae (mW) per ml of blood, respectively. Three groups of Bangkok-strain Cx. quinquefasciatus were allowed to feed on dogs that had 4,800, 5,200, and 5,850 mf per ml of blood. Six groups of Liverpool-strain Ae. aegypti were allowed to feed on dogs with 1,650, 1,950, 3,350, 9,000, 9,250, and 11,550 mf per ml of blood. Three to 4% of Nonthaburi-strain, and 0-6% of Udon Thani-strain Ae. aegypti became infected and had infective-stage larvae (L3) of D. immitis in their probosces. Zero to 1 and 7% of Bangkok-strain Cx. quinquefasciatus had L3 in their probosces after taking blood meals with 4,800 and 5,850 mf per ml of blood, respectively. The percent-infected Liverpool-strain Ae. aegypti with L3 in their probosces were 3-12, 0-12, 10, 16, 7-19, and 0-21 after taking blood meals with 1,650, 1,950, 3,350, 9,000, 9,250, and 11,550 mf per ml of blood, respectively, when tested at different post-blood-feeding days. This study showed both Ae. aegypti and Cx. quinquefasciatus from Thailand can become vectors for D. immitis; however, Liverpool-strain Ae. aegypti are more likely to be competent vectors for D. immitis than Ae. aegypti and Cx. quinquefasciatus from Thailand. The percent infection rates of Ae. aegypti and Cx. quinquefasciatus with D. immitis in the field in Thailand need to be investigated, to confirm the role of these mosquitoes in the life cycle of D. immitis in nature.     

Trends in incidence of hepatocellular carcinoma, 1990-2009, Khon Kaen, Thailand

Background: Liver cancer is the most frequent cancer among Thais especially people in northeastern Thailand, but there has as yet been no assessment of trend. The data of all cancers in Khon Kaen can be retrieved from data base of the Khon Kaen Cancer Registry (KKCR) which was established in 1984. Objective: To assess the incidence trend of hepatocellular carcinoma in Khon Kaen, Thailand, between 1990 and 2009. Methods: Population-based cases of liver cancer registered between 1985 and 2009 were retrieved from the KKCR data base and cases with diagnosis of hepatocellular carcinoma (HCC) with the coding C22.0 according to ICD-O were selected. Incidence trends were calculated using the Jointpoint analysis. Results: There were 7,859 cases of HCC during the study period. Males were affected two times more frequently than females. The most common age group of cases was 50 and 69 years (60.3%). Most patients were diagnosed based on radiology imaging (40.6%) while the morphology verification was 7%. The age-standardized rates (ASR) were 13.1 to 49.8 per 100,000 among males and 4.8 to 38.4 per 100,000 among females depending on year of diagnosis since 1985. Remarkably, the ASRs were clearly low during first few years of starting the registration. The overall ASRs of HCC were 30.3 per 100,000 in males (95% CI: 25.9 to 34.6) and 13.1 per 100,000 (95% CI: 10.4 to 15.8) in females. During 1990-2009, the trends in incidences have been decreasing significantly with the annual percent change (APC) of 6.2% per year (95% CI: –7.6 to –4.8) in males and by 6.5% per year in females (95% CI: –8.4 to –4.9). Conclusions: The incidence trends have been decreasing in both sexes. The recent decline in incidence may represent a falling risk.