Cholesterol homeostasis associated with probiotic supplementation in vivo.

AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai). METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lactobacillus plantarum TAR4 showed the highest cholesterol reduction ability (48·01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration. Rats fed with high-cholesterol diet supplemented with Lact. plantarum TAR4 showed significant reduction in serum total cholesterol (29·55%), serum triglyceride (45·31%) and liver triglyceride (23·44%) as compared to high-cholesterol diet (HCD) group. There was a significant increment in faecal triglyceride (45·83%) and faecal total bile acid (384·95%) as compared to HCD group. CONCLUSIONS: The findings showed that probiotic Lact. plantarum TAR4 supplementation reduced the absorption of bile acids for enterohepatic recycling and increased the catabolism of cholesterol to bile acids and not by suppressing the rate of cholesterol synthesis. SIGNIFICANCE AND IMPACT OF STUDY: Probiotic supplements could provide a new nonpharmacological alternative to reduce cardiovascular risk factors.

Factors affecting intra-oral pH - a review.

One of the greatest challenges to modern dentistry is the progressive destruction of tooth material due to chemical erosion. Dental erosion is the loss of dental hard tissue, without the action of bacteria, in which demineralisation of enamel and dentine results due to a decrease in intra-oral pH. The aim of this review was to appraise the scientific literature on the factors that can affect intra-oral pH. The review will examine (i) the protective role of human saliva, in terms of its mineral composition, flow rates and buffering systems and (ii) sources of in-mouth acids such as extrinsic acids, which are derived from the diet and environment, as well as intrinsic acids, which are related to disorders of the gastro-oesophageal tract. This review may assist clinicians to identify the risk factors for tooth wear and to recommend adequate preventive measures to patients.

Continuous measurement of intra-oral pH and temperature: development, validation of an appliance and a pilot study.

To describe a novel approach for continuous measurement of intra-oral pH and temperature in individuals carrying out normal daily activities over 24 h. We designed, validated and constructed a custom-made appliance fitted with a pH probe and a thermocouple. Six subjects wore the appliance over a 24-h period for two non-consecutive days, while the intra-oral pH and temperature were measured continuously and recorded. Intra-oral pH and temperature were very similar across different recording days, the difference being not statistically significant (P ≥ 0.14). There was a noticeable difference in the pattern of variation of pH between day and night. During the day, the mean pH was 7.3 (±0.4) and dropped markedly only after consumption of acidic food and drinks. The intra-oral pH decreased slowly during sleep with an average pH of 6.6 (±0.4) being recorded. The difference between day and night was statistically significant (P = 0.002). The mean intra-oral temperature was 33.9 °C (±0.9) during daytime and 35·9 °C (±0·5) during sleep (P = 0.013) with minor fluctuations occurring over 24 h. The continuous and simultaneous intra-oral pH and temperature measurement system described in this report is reliable, easy to construct, able to measure variables over a sustained period and may serve as a future diagnostic tool in a number of applications.

Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

Development and validation of algorithms for the detection of statin myopathy signals from electronic medical records.

The purpose of this study was to develop and validate sensitive algorithms to detect hospitalized statin-induced myopathy (SIM) cases from electronic medical records (EMRs). We developed four algorithms on a training set of 31,211 patient records from a large tertiary hospital. We determined the performance of these algorithms against manually curated records. The best algorithm used a combination of elevated creatine kinase (>4× the upper limit of normal (ULN)), discharge summary, diagnosis, and absence of statin in discharge medications. This algorithm achieved a positive predictive value of 52-71% and a sensitivity of 72-78% on two validation sets of >30,000 records each. Using this algorithm, the incidence of SIM was estimated at 0.18%. This algorithm captured three times more rhabdomyolysis cases than spontaneous reports (95% vs. 30% of manually curated gold standard cases). Our results show the potential power of utilizing data and text mining of EMRs to enhance pharmacovigilance activities.

Implantation, embryo-maternal interactions, immunology and modulation of the uterine environment -- a workshop report.

The Workshop discussed five topics which were considered to be topical. 1) A comparison was made between rodents and primates regarding how uNK cells are distributed at the implantation site in these species. 2) The possibility that the functions of uNK cells may be different in mice and humans are discussed. 3) Trophoblast MHC expression in the Rhesus monkey (haemochorial) and the sheep (epitheliochorial) was compared in order the gauge the importance of these molecules in these two fundamentally different types of placentation. 4) New data were presented on the intriguing molecule, HLA-G, whose function is still unclear. 5) A discussion was initiated to debate the role of the innate and the adaptive immune systems in human implantation.

Simultaneous wireless assessment of intra-oral pH and temperature.

OBJECTIVES: Intra-oral pH plays an important role in the pathogenesis of tooth erosion and decay, but there is limited information about its variation in real life settings. The aims of this research were to: 1) develop a wireless device, which can be used to continuously monitor intra-oral pH and temperature in real-time; 2) test and validate the device under controlled laboratory conditions; and 3) collect data in a natural environment in a sample of healthy volunteers. METHODS: A wireless device for measuring pH and temperature simultaneously was developed, calibrated and validated against the gold standard glass electrode pH meter. A smart phone was used as data logger. The wireless device was embedded in an oral appliance and worn by eleven participants (mean age 31.1±6.9years) for 24h, while conducting standardised drinking tasks and regular daily activities. RESULTS: The wireless device could accurately measure pH and temperature both in vitro and in vivo. The recovery time following the swallow of a standard acidic drink varied markedly among individuals (mean=1.3±0.9min). The intra-oral pH and temperature recorded in the natural environment also showed a large inter- and intra-individual variability. The average intra-oral pH when asleep (6.7±0.5) was lower (p<0.001) than when awake (7.2±0.5). The average intra-oral temperature during sleep (35.6±0.5°C) was higher (p<0.001) than when awake (34.5±0.7°C). CONCLUSIONS: Intra-oral pH and temperature can be continuously and wirelessly assessed in real-life settings, and show individual-specific patterns with circadian variations. Intra-oral pH becomes slightly acidic during sleep while intra-oral temperature increases and fluctuates less. CLINICAL SIGNIFICANCE: We propose a wireless device that is capable of measuring intra-oral pH over a 24-h period. We found marked inter-individual variation after acidic stimuli, and day to sleep time variation of both intra-oral temperature and pH. Our approach may provide new insight into the relationship between oral pH, tooth wear and decay.

Improved protection from velogenic Newcastle disease virus challenge following multiple immunizations with plasmid DNA encoding for F and HN genes.

Specific-pathogen free (SPF) chickens were inoculated with the plasmid constructs encoding the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of Newcastle disease virus (NDV), either individually or in combination and challenged with velogenic NDV. The antibody level against NDV was measured using commercial enzyme linked immunosorbent assay (ELISA). In the first immunization regimen, SPF chickens inoculated twice with NDV-F or NDV-HN constructs elicited antibody responses 1 week after the second injection. However, the levels of the antibody were low and did not confer significant protection from the lethal challenge. In addition, administration of the plasmid constructs with Freund's adjuvant did not improve the level of protection. In the second immunization regimen, chickens inoculated twice with the plasmid constructs emulsified with Freund's adjuvant induced significant antibody titers after the third injection. Three out of nine (33.3%) chickens vaccinated with pEGFP-HN, five of ten (50.0%) chickens vaccinated with pEGFP-F and nine of ten (90.0%) chickens vaccinated with combined pEGFP-F and pEGFP-HN were protected from the challenge. No significant differences in the levels of protection were observed when the chickens were vaccinated with linearized pEGFP-F. The results suggested that more than two injections with both F and HN encoding plasmid DNA were required to induce higher level of antibodies for protection against velogenic NDV in chickens.