Safety Assessment of Streptococcus salivarius UBSS-01 in Rats and Double-Blind Placebo-Controlled Study in Healthy Individuals.

Streptococcus salivarius is a common, harmless, and prevalent member of the oral microbiota in humans. In the present study, the safety of S. salivarius UBSS-01 was evaluated using in silico methods and preclinical and clinical studies. In an acute toxicity study, rats were administered with 5 g/kg (500 × 109 CFU) S. salivarius UBSS-01. The changes in phenotypic behaviors and hematological, biochemical, electrolytes, and urine analyses were monitored. No toxicity was observed at 14 days post-treatment. The no observable effects limit (NOEL) of S. salivarius UBSS-01 was >5 g/kg in rats. In a 28-day repeat dose toxicity study, rats were administered S. salivarius UBSS-01 once daily at doses of 0.1, 0.5, and 1 g/kg (10, 50, and 100 billion CFU/kg, respectively) body weight. S. salivarius UBSS-01 did not influence any of the hematology parameters and clinical chemistry parameters in plasma and serum samples after 28-day repeated administration. No structural abnormality was observed in the histological examination of organs. Whole genome analysis revealed the absence of virulence factors or genes that may transmit antibiotic resistance. In the double-blind study with 60 human participants (aged 18-60 years), consumption of S. salivarius UBSS-01 for 30 days was found to be safe and results were comparable with placebo treatment These findings indicate that S. salivarius UBSS-01 may be safe for human consumption.

Oral Supplementation of Collagen Peptides Improves Skin Hydration by Increasing the Natural Moisturizing Factor Content in the Stratum Corneum: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: We aimed to investigate the effect of orally ingested collagen peptides (CPs) on skin condition and elucidate their mechanism of action. METHODS: A randomized, placebo-controlled, double-blind trial was conducted in 99 healthy Japanese women, aged 35-50 years. The subjects were randomized into 3 groups (33 subjects/group) to receive 1 or 5 g of CP or placebo once daily for 12 weeks. Skin water content, transepidermal water loss (TEWL), skin elasticity, and skin thickness were evaluated before treatment and after 4, 8, and 12 weeks of treatment. The level of natural moisturizing factor (NMF) constituents in the stratum corneum (SC) was quantified before treatment and after 12 weeks of treatment. RESULTS: Oral ingestion of CP increased the water content in the SC and epidermis and decreased TEWL. Furthermore, the NMF level in the SC was increased. However, skin elasticity and skin thickness remained unchanged. CONCLUSIONS: The improvement in skin water content following the oral ingestion of CP can be attributed to an increase in the level of NMF in the SC. TRIAL REGISTRATION: UMIN000030375 (retrospectively registered).

Oral intake of lingonberry and amla fruit extract improves skin conditions in healthy female subjects: A randomized, double-blind, placebo-controlled clinical trial.

In this study, we examined the effect of ingestion of lingonberry and amla fruit extract (LAE) on several human skin conditions. To conduct a randomized, double-blinded, placebo-controlled study, we randomly divided 99 healthy female subjects into three groups; the first group received a drink containing 25 mg of lingonberry extract and 30 mg of amla fruit extract; the second group received a drink containing double the volume of extracts received by the first group; and the third group received a placebo drink. Each participant drank 50 mL of their assigned drink once daily for 12 weeks. The primary endpoint was skin elasticity, and the secondary endpoints included skin thickness, stratum corneum water content, and degree of wrinkles around the eyes. After 12 weeks of LAE drink intake, skin elasticity showed significant, dose-dependent improvements (P < 0.01). Skin thickness, stratum corneum water content, and the degree of wrinkles also significantly improved (P < 0.001) in a dose-dependent manner. The improvements in skin elasticity and thickness, as well as in the stratum corneum water content and the degree of wrinkles, observed upon oral intake of LAE indicate that LAE may be considered a candidate anti-aging agent for preventing skin weakening.

Aripiprazole in treatment of Gilles de la Tourette syndrome - New therapeutic option.

Aripiprazole is a dopamine D2- and serotonin 5-hydroxytryptamine (5-HT)1A receptor partial agonist and 5-HT2A receptor antagonist primarily used for the treatment of schizophrenia, bipolar disorder or depression with psychotic ideation. However, recently a number of new possible indications have been suggested, among them Gilles de la Tourette syndrome (GTS). In two randomized, double-blind, placebo-controlled studies in children and adolescents with GTS has been confirmed the efficacy of aripiprazole in tic reduction. In comparison to other neuroleptics, aripiprazole seems to be similarly effective. What is more, the number and profile of possible adverse effects is also favorable. As a consequence, aripiprazole had been registered by Food and Drug Administration (FDA) for the treatment of tics and represents new therapeutic option in treatment of GTS.

[Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid]. / Farmakoterapiia sindroma defitsita vnimaniia s giperaktivnost'iu u detei: rezul'taty mnogotsentrovogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniia gopantenovoi kisloty.

AIM: To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups. MATERIAL AND METHODS: One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention. RESULTS AND CONCLUSION: There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

Denosumab: a cost-effective alternative for older men with osteoporosis from a Swedish payer perspective.

OBJECTIVE: To assess the cost-effectiveness of denosumab versus other treatments in men with osteoporosis who are ≥75years old from a payer perspective in Sweden. METHODS: A lifetime cohort Markov model was developed with seven health states: well, hip fracture, vertebral fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Estimates of fracture efficacy were drawn from available studies in post-menopausal osteoporotic (PMO) women as BMD improvements have been shown to be similar across male osteoporosis (MOP) and PMO populations, and a recent clinical trial suggested that the fracture risk reduction from bisphosphonate therapy in men is similar to that seen in women in comparable studies. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, ibandronate, zoledronate, strontium ranelate and teriparatide. On average, patients in the model were 78years old, with bone mineral density T-score at the femoral neck of -2.12. Prevalent vertebral fractures were present in 23% of patients. In the base-case, the model assumed that patients would experience treatment-related effects up to 2years after discontinuation. Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. RESULTS: Total lifetime costs for denosumab, alendronate, strontium ranelate, zoledronate, risedronate, ibandronate and teriparatide were €31,004, €33,731, €34,788, €34,796, €34,826, €35,983 and €37,461, respectively. Total QALYs were 5.23, 5.15, 5.15, 5.17, 5.13, 5.12 and 5.22, respectively. Compared to other treatments, denosumab had the lowest costs and highest QALYs. In the one-way sensitivity analyses, when compared to alendronate (next least expensive strategy), the ICER for denosumab was most sensitive to the relative risk of hip fracture on denosumab. The probability of denosumab being cost-effective compared to the other treatments at a threshold of €66,000/QALY was 96.1%. CONCLUSION: Denosumab dominated all comparators, including generic bisphosphonates, in the treatment of osteoporosis in men who were ≥75years old in Sweden.

The Effect of Red-Yeast-Rice Supplement on Serum Lipid Profile and Glucose Control in Subjects with Impaired Fasting Glucose or Impaired Glucose Tolerance

This study was aimed at evaluating the effect of red-yeast-rice supplementation on cholesterol-lowering and glucose control in subjects with impaired fasting glucose (IFT) or impaired glucose tolerance (IGT). We conducted a doubleblind, placebo-controlled study with 3 groups ; placebo, low dose group (red yeast rice 210.0 mg/capsule, 2.52 g/day)and high dose group (red yeast rice 420.0 mg/capsule, 5.04 g/day), which were randomly assigned to subjects with impaired fasting glucose or impaired glucose tolerance. We measured fasting serum concentrations of total-, LDL-, HDL-cholesterol, triglyceride, glucose, insulin, free fatty acid (FFA) and 2 h oral glucose tolerence test (OGTT) before and after the supplementation. Both low dose and high dose groups had significant decrease in LDL cholesterol and atherogenic index (AI) compared with placebo group (p < 0.05). Additionally, total and HDL cholesterol improved significantly in high dose group compared with placebo group (p < 0.05). Fasting serum glucose decreased in test groups and increased in placebo group after intervention. However, it was not significant differences. In subjects which fasting blood glucose is more than 110 mg/dL, fasting glucose had a tendency to decrease in high dose group (p < 0.1) and Hemoglobin A1c (HbA1c) had significant decrease in low dose group (p < 0.05), while insulin and HOMA-IR had a tendency to increase in placebo group after intervention. Mean changes of glucose related parameters (fasting glucose, insulin, HOMA-IR) compared with placebo group did not show significant differences. In conclusion, subjects with impaired fasting glucose or impaired glucose tolerance were significantly improved in serum lipid profile by red yeast rice supplementation without serious side effects. These are more effective in the case of a high dose. The effects of red yeast rice supplementation on glucose control were insignificant.