OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats.
MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon.
RESULTS: APME or APAE pretreatment significantly (p
OBJECTIVES: We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings.
METHODS: Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations.
RESULTS: DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/μL (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations.
CONCLUSIONS: DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.
METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).
CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
METHODS: Two pneumococcal Brunei clinical strains were serotyped by multiplex PCR method using oligonucleotide sequences derived from Centers for Disease Control and Prevention. A validated immortalised mouse brain endothelial cell line (bEnd.3) was used as a brain endothelium model for the study of the pneumococcal breach of the blood-brain barrier using an adherence and invasion assay.
RESULTS: Both of the pneumococcal clinical strains were found to be serotype 19F, a common circulating serotype in Southeast Asia and globally and possess the ability to adhere and invade the brain endothelial cells.
CONCLUSION: In addition, this is the first report on the serotype identification of pneumococci in Brunei Darussalam and their application on a brain endothelium model. Further studies are required to understand the virulence capabilities of the clinical strains.
METHODS: PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel-Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity.
DISCUSSION: Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.
TRIAL REGISTRATION: Clinicaltrials.gov, NCT03056391 . Registered on 12 October 2016.
METHODS: This multicenter, parallel, open-label, randomized controlled trial investigated the clinical efficacy of WPS in 126 malnourished CAPD patients with serum albumin <40 g/L and body mass index (BMI) <24 kg/m2. Patients randomized to the intervention group (IG, n = 65) received protein powder (27.4 g) for 6 months plus dietary counseling (DC) while the control group (CG, n = 61) received DC only. Anthropometry, biochemistry, malnutrition-inflammation-score (MIS), dietary intake inclusive of dialysate calories, handgrip strength (HGS) and quality of life (QOL) were assessed at baseline and 6 months. Clinical outcomes were assessed by effect size (Cohen's d) comparisons within and between groups.
RESULTS: Seventy-four patients (n = 37 per group) completed the study. Significantly more IG patients (59.5%) achieved dietary protein intake (DPI) adequacy of 1.2 g/kg per ideal body weight (p 0.05). A higher DPI paralleled significant increases in serum urea (mean Δ: IG = +2.39 ± 4.36 mmol/L, p = 0.002, d = 0.57 vs CG = -0.39 ± 4.59 mmol/L, p > 0.05, d = 0.07) and normalized protein catabolic rate, nPCR (mean Δ: IG = +0.11 ± 0.14 g/kg/day, p 0.05, d = 0.09) for IG compared to CG patients. Although not significant, comparison for changes in post-dialysis weight (mean Δ: +0.64 ± 1.16 kg vs +0.02 ± 1.36 kg, p = 0.076, d = 0.58) and mid-arm circumference (mean Δ: +0.29 ± 0.93 cm vs -0.12 ± 0.71 cm, p = 0.079, d = 0.24) indicated trends favoring IG vs CG. Other parameters remained unaffected by treatment comparisons. CG patients had a significant decline in QOL physical component (mean Δ = -6.62 ± 16.63, p = 0.020, d = 0.47). Using changes in nPCR level as a marker of WPS intake within IG, 'positive responders' achieved significant improvement in weight, BMI, skinfold measures and serum urea (all p 0.05).
CONCLUSION: A single macronutrient approach with WPS in malnourished CAPD patients was shown to achieve DPI adequacy and improvements in weight, BMI, skin fold measures, serum urea and nPCR level. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov (NCT03367000).
METHODS: This cross-sectional study aimed to evaluate (i) the effect of FTO rs9930506 on obesity and related parameters and (ii) the influence of diet on the above association in Malaysian adults. In total, 79 obese and 99 nonobese Malaysian adults were recruited.
RESULTS: In comparison with Chinese and Malays, Indians had significantly higher waist circumference (P ≤ 0.001 and P = 0.016), waist-hip ratio (P = 0.001 and P < 0.001), body fat percentage (P = 0.001 and P = 0.042), fasting insulin (P = 0.001 and P = 0.001), homeostatic model assessment-insulin resistance (P = 0.001 and P = 0.001) and lower high-density lipoprotein-cholesterol levels (P < 0.001 and P < 0.001), respectively. Indians consumed significantly lower dietary cholesterol (P = 0.002), percentage energy from protein (P < 0.001) and higher fibre (P = 0.006) compared to the other two groups. Malaysian Indians expressed the highest risk allele frequency (G) of FTO rs9930506 compared to the Malays and the Chinese (P < 0.001). No significant association was found between FTO rs9930506 and obesity (dominant model). Risk allele carriers (G) consumed significantly lower vitamin E (P = 0.020) and had a higher fibre intake (P = 0.034) compared to the noncarriers (A). Gene-diet interaction analysis revealed that risk allele carriers (G) had lower high sensitivity C-reactive protein (hsCRP) levels with higher energy from protein (≥14% day-1 ; P = 0.049) and higher vitamin E (≥5.4 mg day-1 ; P = 0.038).
CONCLUSIONS: The presence of the risk allele (G) of FTO rs9930506 was not associated with an increased risk of obesity. Malaysian Indians had a significantly higher frequency of the risk allele (G). Indian participants expressed higher atherogenic phenotypes compared to Chinese and Malays. FTO rs9930506 may interact with dietary protein and vitamin E and modulate hsCRP levels.
METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).
RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.
CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.
OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.
MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.
RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.
DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.