Sivalingam Nalliah

Is there a genetic variation association in the IL-10 and TNF α promoter gene with gestational diabetes mellitus?

Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance diagnosed for the first time during pregnancy, affects both maternal and fetal health. Possession of a specific genetic polymorphism can be a predisposing factor for susceptibility to some diseases. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNP) in the promoter gene of interleukin-10 (IL-10) as well as tumor necrosis factor-alpha (TNF alpha) with the development of GDM. Two hundred and twelve consecutive series of eligible normal pregnant women (controls) and gestational diabetes mellitus women were selected based on the studys inclusion and exclusion criteria. DNA was extracted from blood and genotyped for IL-10 at three positions and TNF alpha for gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of IL-10 and TNF alpha at different gestational periods as well as postpartum were quantified using enzyme linked immunosorbent assay (ELISA). The results of the study showed that the difference in the frequency of SNP at position -597 in the promoter of the human IL-10 gene between the control and GDM groups was statistically significant (p < 0.05). In contrast, there was no significant difference in the frequency of SNP at the other two sites in the promoter region of the human IL-10 gene (-824 and -1082) as well as position -308 in the promoter of the human TNF-alpha (p > 0.05). In addition, there was no significant difference between the two groups in terms of plasma levels of IL-10 as well as TNF alpha in different stages of pregnancy. SNP at position -597 was significantly associated with the development of GDM and shows potential for use as a predictive marker for GDM.

Association between polymorphisms in human tumor necrosis factor-alpha (−308) and -beta (252) genes and development of gestational diabetes mellitus

OBJECTIVE The aim of this study is to investigate if an association exists between single nucleotide polymorphism (SNP) in the tumor necrosis factor-alpha (TNF-alpha) and TNF-beta genes. METHODS The DNA was extracted and SNP in the human TNF-alpha and TNF-beta genes at positions -308 (G/A) and 252 (A/G), respectively, was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of TNF-alpha in different stages of pregnancy were quantified using enzyme linked immunosorbent assay (ELISA). RESULTS There was no significant difference in genotype and allele frequency of SNP at position -308 (G/A) in the promoter region of the human TNF-alpha gene as well as the SNP at position 252 (A/G) in the human TNF-beta gene between the GDM and control subjects. Using the logistic regression model, it was found that the SNP in the TNF-alpha as well as TNF-beta were not associated with development of GDM. In addition, the TNF-alpha levels in the plasma of GDM and control mothers were not significantly different. CONCLUSIONS In the population studied, the SNP in position -308 (G/A) of the human TNF-alpha or in position 252 (A/G) of the human TNF-beta gene is not an independent risk factor or a predictor for GDM.

Is there a place for selective vaginal breech delivery in Malaysian hospitals: experiences from the Ipoh hospital

Background. The ‘Term Breech Trial’ (TBT) results of 2001 have impacted on the mode of delivery of breech with a low threshold for caesarean delivery (CD) worldwide. Aims. The trends in mode of delivery in developing countries have also changed. The aims of this retrospective analysis of all breech presentation was to see if similar trends are seen in Ipoh Hospital in Malaysia and if perinatal outcome is affected by mode of delivery. Methods. All breech pregnancies presenting in the labour at the Ipoh Hospital, Malaysia, irrespective of gestation or booking status were analysed with respect to mode of delivery, fetal outcome and maternal mortality. Results. Out of 4886 breech presentation between 1992 and 2004, 3725 cases were evaluable. The prevalence of breech at birth was 3%. Vaginal breech deliveries decreased from 70.4% in 1994 to 13.1% in 2004. Consequently, CDs rose to 86.9% in CDs. There were 107 perinatal deaths (1994–2004) in the series and the crude perinatal mortality rate (PNMR) was four times higher than the hospital PNMR (11.4/1000 in 2004). Conclusion. Although the CD rates rose exponentially with the release of the ‘TBT’, the mode of delivery did not impact on better PNMR in breech cases in this hospital. The need for selective vaginal births for breech, increased use of external cephalic version and the long implications of a uterine scar in future pregnancies in the ‘shared antenatal care in the local context in a developing country is discussed.

Biochemical evaluation of the supporting structure of pelvic organs in selected numbers of premenopausal and postmenopausal Malaysian women.

CONTEXT Pelvic organ prolapse (POP) is associated with menopause and changes in the proteins of the pelvic supporting system, but there is scant data on the precise alterations in Malaysian women. AIM The aim of this study is to determine the differences in the extracellular matrices (ECM) of uterosacral ligaments in premenopausal and postmenopausal Malaysian women with or without POP. SETTINGS AND DESIGN The observational study was conducted for 9 months in three general hospitals involving 30 women who underwent hysterectomies for various indications except for carcinoma of pelvic organs. MATERIALS AND METHODS Three groups were identified: Premenopausal women (Group 1), postmenopausal women without POP (Group 2), and postmenopausal women with POP (Group 3). Age, duration of menopause, body mass index (BMI), parity, and vaginal deliveries were documented. Only 21 samples of the uterosacral ligaments were stained immunohistochemically for collagen I and III, matrix metalloproteinases (MMPs) 1 and 2, elastin, and tenascin. STATISTICAL ANALYSIS USED Image J software analysis was utilized for quantification, while non-parametric statistics (Kruskal-Wallis with post-hoc Dunns Multiple Comparison test) was used for result analysis. RESULTS The profile parameters were not significantly different except for mean age and duration of menopause in Group 3. Samples from Group 2 showed lower expression of almost all proteins except MMP1 and tenascin (higher) as compared to Group 1. The changes appeared to be exaggerated in Group 3, though statistically insignificant. CONCLUSION A significant difference in the expression of ECM was apparent in postmenopausal subjects as compared to premenopausal (P=0.05), compromising the uterosacral ligament tensile strength. The findings are proven similar as those changes in women from other studies.

Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH) - a prospective follow-up study

BackgroundHypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry.MethodsVenous blood samples (antepartum, intrapartum and post partum periods) were drawn to estimate for sFlt-1 and PlGF levels while placental tissue samples were examined for placental morphometry.ResultsPlGF levels were lower in gestational hypertension (GH) compared to normotensive during antepartum and intrapartum period, whereas sFlt-1 levels were elevated in GH at antepartum, intrapartum and postpartum intervals during pregnancy. An inverse relationship between these two biomarkers was observed through correlation analysis. PlGF levels were inversely correlated with total villous surface area of the placental periphery (TCsa-C) and villous capillarization (VC-C) of the placental periphery.ConclusionWe established periodic values of for sFlt-1 and PlGF levels for the first time in an ethnically diverse Malaysian setting. We suggest the development of GH in women is related to defective capillarization. In demonstrating periodic changes, this study suggest the possibility of developing GH and other long term health complications as a result of prolonged exposure to sFlt-1. The correlation between PlGF levels and morphometric findings also support possible capillarization defect.

Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis

Abstract Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to −80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid ‘burst release’ of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the ‘non-formulated’ drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.

An association between IL-10 promoter polymorphisms and diabetic nephropathy: a meta-analysis of case-control studies

BackgroundThis study aimed to synthesize evidence on the association between IL-10 gene (−819 C/T, −1082 A/G, −592 A/C) polymorphisms and the risk of developing diabetic nephropathy.MethodsA systematic literature search was done in health-related electronic databases. The search was limited to studies published in English until September 2017. We also checked the references of retrieved articles and relevant reviews for any additional studies. The methodological quality of the studies included in this review was assessed using the ‘Scales for Quality Assessment’. The I2 test was used to quantify between-study heterogeneity. A value of I2 > 50% indicated substantial heterogeneity. For the pooled analysis, summary odds ratio (OR) and its 95% confidence interval (CI) in random effect model were used.ResultsEight case-control studies (1192 cases with diabetic nephropathy and 2399 controls) met the inclusion criteria. Three groups of people namely Africans, Asians and Caucasians were included in this review. There were significant protective effects of SNP -819 C/T in overall population (OR 0.32, 95% CI 0.26–0.4) and − 1082 A/G SNP in the Asian population (OR 0.64, 95% CI 0.47–0.86) on diabetic nephropathy in the recessive model. There was no significant effect of −592 A/C on diabetic nephropathy.ConclusionThe findings suggest the protective effects of −1082A/G and -819G/A polymorphisms on the risk of developing diabetic nephropathy in type 2 diabetes mellitus, especially in the Asian population. Well- designed, prospective studies with sufficient number of participants are recommended to substantiate these findings.

Cervical pessary in the prevention of preterm births in multiple pregnancies with a short cervix: PRISMA compliant systematic review and meta-analysis

Abstract Background: Preterm births occur frequently in multiple pregnancies with a short cervix. The cervical pessary is a potential intervention for prevention of preterm births. Objective: To assess the effectiveness of cervical pessary in the prevention of preterm births in multiple pregnancies with a short cervix (<25 mm). Search strategy: Major databases from 2006 to 20th November 2016 were searched for relevant terms. Selection criteria: We included randomized controlled trials that assessed the effectiveness of cervical pessary on pregnancy outcomes in multiple pregnancies with a short cervix. Data collection and analysis: Risk ratio was used as the summary measure with random effects model. We assessed heterogeneity between studies using the I2 index. Quality assessment was done based on Cochrane Handbook Method. Main results: Pooled data showed no benefit of using cervical pessary in the prevention of preterm births, birth weights less than 1500 g, less than 2500 g, adverse neonatal events and fetal/neonatal deaths in twin pregnancies with a short cervix. Conclusion: We are unable to show benefit of using cervical pessary in preventing preterm births in twin pregnancies with a short cervix. However, as cervical pessary is a reasonable intervention, there is a need for more randomized controlled trials in this area.