Search

Objective: Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp)., Methods: Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively., Results: Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P < 0.01), which were associated with a significant increase in urinary excretion of sodium. Addition of diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp., Conclusion: These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.

Purpose: Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, may be beneficial in obese diabetic patients based on its potential to decrease blood glucose and body weight, but there is limited proof. This analysis aimed to investigate the efficacy and safety of luseogliflozin in patients with varying levels of obesity., Methods: A pooled analysis of four 52-week Phase III trials of luseogliflozin 2.5 mg daily (or up to 5 mg daily) in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index (BMI) was conducted. Efficacy end points included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight., Findings: In total, 1031 patients were included and stratified into 5 BMI (kg/m(2)) groups: low-to-medium (<22.5, n = 222); medium (≥22.5 to <25, n = 270); high-level 1 (≥25 to <27.5, n = 262); high-level 2 (≥27.5 to <30, n = 142); and very-high (≥30, n = 135). HbA1c decreased significantly compared with baseline until week 52 in all groups, and a similar trend was observed with FPG and body weight. The reduction in glycemic parameters tended to be slightly smaller in patients with BMI <22.5 kg/m(2), and the reduction in body weight tended to be greater in patients with higher BMI, especially those with BMI ≥30 kg/m(2). Levels of fasting insulin, C-peptide immunoreactivity, triglyceride, blood pressure, aspartate aminotransferase, alanine aminotransferase, and uric acid decreased significantly at week 52 in all groups (except for aspartate aminotransferase in patients with BMI <22.5 kg/m(2)). Levels of these parameters tended to be higher at baseline and these enhanced levels resulted in a greater decrease in patients with higher BMI. In safety, the incidence of adverse events was similar between groups, and most of them were mild in severity., Implications: HbA1c and body weight decreased significantly in all groups. Decrease in glycemic parameters tended to be smaller in patients with BMI <22.5 kg/m(2), while that of body weight was larger in patients with higher BMI. Furthermore, luseogliflozin was especially beneficial in patients with higher BMI in terms of metabolic abnormalities, including insulin secretion and hypertension. Luseogliflozin exhibited a favorable and similar safety profile over 52 weeks in all groups. This agent can be an effective and well-tolerated therapeutic option in patients with a wide range of BMI levels, and it may be more beneficial in patients with higher BMI., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin., Methods: In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0-10.0%] and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m(2) were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m(2)): normal (≥90; n = 13; normal group), normal-to-mildly reduced renal function (≥75 to <90; n = 12; normal-mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild-moderate group)., Results: The mean [95% confidence interval (CI)] placebo-subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was -24.39 (-32.53, -16.26), -28.28 (-39.35, -17.22), and -11.53 (-23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was -26.9 (-46.9, -6.9), -38.1 (-59.6, -16.6), and 1.5 (-25.5, 28.4) in the normal, normal-mild, and mild-moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal-mild (121.0 vs. 97.9), and mild-moderate (104.0 vs. 91.1) groups., Conclusion: This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function., Trial Registration: JapicCTI-142548., Funding: Taisho Pharmaceutical Co., Ltd.

Objective: Because of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes., Design: Systematic review and network meta-analysis., Data Sources: MEDLINE and EMBASE were searched from January 2005 to January 2015., Eligibility Criteria: Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods., Results: In monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300-2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26)., Conclusions: There were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction of local anesthetic proved application of epidural (EP) as an effective and safe way of an analgesia in intra- and the post-operational period and now it is widely applied at children of all age groups (1). However there is a number of contraindications for application of this type of an analgesia. At children till 6 months lower dosages of a ropivacain of 2 mg/kg are applied, considering their age features. At the phenomena of system toxicity infusion of 20% lipofundin is applied. The child has an age 1.5 months, weight 5230 g, with the diagnosis a cystous dysplasia of both kidneys, a megaureter at the left and on the right, lack offunction of the left kidney operation a laparoscopic nefrureterektomia is executed at the left. In the postoperative period at application of EP of an analgesia ofropivacain 2 mg/ml by a drop way introduction in a standard dosage of 0.2 mg/kg of body weight an hour the repeating episodes of convulsions which were regarded as manifestation of toxic properties of local anesthetic were noted. Infusion of 20% lipofundin of 15 ml (2.8 ml/kg of body weight) within 30 minutes with a positive effect was applied. EP an analgesia was recoloured.

Purpose: To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin (TS-071) in Japanese patients with type 2 diabetes mellitus (T2DM)., Methods: Study 1 was a 52-week, Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin (or increased to 5 mg/d) in patients with T2DM with moderate renal impairment. During the initial 24 weeks, efficacy and safety of luseogliflozin were compared with placebo. Study 2 was a pooled analysis of four 52-week, Phase III studies of luseogliflozin, including Study 1, to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function. Patients were stratified into 3 groups by baseline estimated glomerular filtration rate (eGFR): normal renal function (≥90 mL/min/1.73 m(2)), mild impairment (≥60 to <90 mL/min/1.73 m(2)), and moderate impairment (≥30 to <60 mL/min/1.73 m(2)). Patients with moderate impairment were further divided into those with mild-moderate (≥45 to <60 mL/min/1.73 m(2)) and moderate-severe (≥30 to <45 mL/min/1.73 m(2)). In both studies, efficacy end points included changes in glycated hemoglobin (HbA1c) level, fasting plasma glucose (FPG) level, and body weight. The safety end points included adverse events (AEs) and laboratory parameters., Findings: In Study 1, HbA1c, FPG, and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo, with the decrease in these parameters also observed with luseogliflozin at Week 52. The incidence of AEs was similar between groups. In Study 2, 1030 patients were included (normal, 275; mildly impaired, 598; and moderately impaired, 157). At Week 52, HbA1c, FPG, and body weight were significantly decreased from baseline in all groups. In between-group comparisons, the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function; however, the HbA1c-lowering efficacy was reduced by nearly half, whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group. Furthermore, a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR. The incidence of AEs during 52 weeks was similar among all groups, with the majority being mild., Implications: Luseogliflozin improved glycemic control and reduced body weight in all eGFR groups, and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment. Luseogliflozin was well tolerated and safe, with no significant safety issues identified, regardless of baseline eGFR. The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center, and the study registry identification numbers are JapicCTI-111507, JapicCTI-111508, JapicCTI-111509, and JapicCTI-111543., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple doses of luseogliflozin administered once daily for 7 days in Japanese patients with T2DM., Methods: We conducted a randomized, placebo-controlled, single-blind, parallel-group, clinical pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics (including changes in UGE and plasma glucose concentrations), and safety of luseogliflozin., Results: The plasma concentrations of luseogliflozin and its active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was greater in all luseogliflozin groups versus placebo. Least-squares mean differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, respectively. On Day 7, the areas under the concentration-time curves for post-meal plasma glucose and the mean plasma glucose for 0-16 h were significantly lower in all luseogliflozin groups versus placebo. Seven patients had mild adverse events (AEs); all were resolved. No AEs led to study discontinuation., Conclusion: Once-daily administration of luseogliflozin for 7 days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was well tolerated in Japanese patients with T2DM. The pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this study supports its once-daily dosing regimen., Funding: Taisho Pharmaceutical Co., Ltd.

Objective: The effects of activated charcoal (AC) mixed with cathartics for gastric decontamination in the management of organophosphate (OP) poisoning remain unknown due to limited clinical evidence. This exploratory study assessed the effectiveness of premixed AC-sorbitol as a treatment for OP poisoning., Materials and Methods: This retrospective observational case study included patients who either did not receive AC-sorbitol or received a single dose of AC-sorbitol within 24 h after OP ingestion. The patients were divided into three groups: no AC-sorbitol treatment, patients who received AC-sorbitol within 1 h of OP ingestion, and patients who received AC-sorbitol more than 1 h after OP ingestion. Mortality, the development of respiratory failure, and the duration of mechanical ventilation were used as outcome measurements for effectiveness, whereas aspiration pneumonia and electrolyte imbalance were employed as safety measurements., Result: Among 262 patients with OP poisoning, 198 were included. Of these, 133 patients did not receive AC-sorbitol, whereas 14 and 51 patients received AC-sorbitol within 1 h or more than 1 h after ingestion, respectively. The time from ingestion to hospital arrival and time from ingestion to administration of atropine and pralidoxime differed among the groups, whereas other characteristics, including age, amount ingested, and type of ingested OP, were similar among the groups. Univariate and multivariate analysis demonstrated that the administration of AC-sorbitol was not associated with outcome measures for effectiveness and did not significantly increase either aspiration pneumonia or electrolyte imbalances during hospitalization., Discussion and Conclusion: The administration of AC-sorbitol exerted neither beneficial nor harmful effects on the outcomes of OP-poisoned patients regardless of the time from OP ingestion to administration, compared with those of patients who did not receive AC-sorbitol. However, this study enrolled a small number of patients who received AC-sorbitol; further qualified trials with a sufficient number of patients are therefore needed.

SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD) the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

Luseogliflozin, a selective sodium glucose cotransporter 2 inhibitor, was demonstrated in a previous 24-week study of type 2 diabetic patients to be efficacious and well tolerated. This study mainly aimed to evaluate the long-term safety of luseogliflozin monotherapy in Japanese type 2 diabetic patients based on the Japanese guidelines. Additionally, long-term efficacy was also evaluated. Patients on diet and exercise therapy alone with an HbA1c of 6.9-10.5% received luseogliflozin 2.5 mg once daily for 52 weeks. For patients with insufficient glycemic control, this dose was able to be increased to 5 mg at Week 24. Adverse events (AEs), clinical laboratory tests, vital signs and 12-lead electrocardiograms were used to assess safety. Efficacy endpoints consisted of changes in HbA1c, fasting plasma glucose (FPG), and body weight from baseline. Of 299 patients who received luseogliflozin, 279 completed the study. Most AEs were mild in severity with incidences of AEs and adverse drug reactions at 75.3% and 16.7%, respectively. Although hypoglycemia was observed in 7 patients (2.3%), no major hypoglycemic episodes occurred. The incidences of AEs of special interest, including pollakiuria, volume depletion and urinary tract/genital infections, were at acceptable levels. Luseogliflozin significantly lowered HbA1c (-0.50%, P< 0.001), FPG (-16.3 mg/dL, P< 0.001) and body weight (-2.68 kg, P< 0.001) at Week 52 compared to baseline. Up-titration to 5 mg further improved glycemic control. In this long-term study of Japanese type 2 diabetic patients, luseogliflozin monotherapy was well tolerated for 52 weeks and provided a sustained glycemic lowering effect and reduced body weight.

Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that was recently approved for marketing and launched in Japan to treat T2DM., Areas Covered: This review summarizes the published data regarding the mechanism of action, clinical efficacy, and safety of luseogliflozin for treating T2DM. Other potential benefits of luseogliflozin, including lowering body weight and blood pressure, beyond its glucose-lowering effects are also discussed., Expert Opinion: Luseogliflozin lowers plasma glucose concentration and body weight, and has beneficial effects on other clinically relevant parameters, including blood pressure and uric acid, in patients with T2DM. Although it had a good safety profile in clinical trials, there may be some safety concerns, including a possible decrease in muscle mass and an increase in ketone bodies. Therefore, careful administration and consideration of its benefit-risk balance are necessary. When using luseogliflozin, it is important to select appropriate patients and to adhere to its guidelines for use. If used correctly, luseogliflozin is expected to be positioned as a new type of oral hypoglycemic drug for treating T2DM.

Treatment of type 2 diabetes mellitus (T2DM) continues to present challenges, with many patients failing to achieve glycemic targets. Despite the availability of many oral and injectable anti-diabetic agents, therapeutic efficacy is often offset by undesirable side effects such as hypoglycemia, weight gain and cardiovascular complications. Therefore, the search for new therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron via the sodium/glucose co-transporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral anti-diabetes, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action. Canagliflozin and dapagliflozin in US market, and ipragliflozin and luseogliflozin in Japan market are now available for glycemic control in type 2 diabetics. There are several phase III clinical ongoing trials involving this new class of medications. This review examines some of the key efficacy and safety data from clinical trials of the SGLT2 inhibitors approved, and their future perspectives in the treatment of T2DM.

Objective: Luseogliflozin is a novel sodium glucose cotransporter 2 inhibitor for type 2 diabetes mellitus (T2DM) treatment. An exploratory Phase II study was conducted to assess the efficacy and safety of several doses of luseogliflozin in Japanese T2DM patients., Patients and Methods: Japanese T2DM patients aged 20-74 years with hemoglobin A1c (HbA1c) of 6.9-10.5%, fasting plasma glucose (FPG) ≥126 mg/dL and on diet therapy were randomized in a double-blind manner to receive luseogliflozin (0.5, 2.5, or 5 mg) or placebo once daily for 12 weeks (n = 61, 61, 61, and 56, respectively). The primary endpoint was the change in HbA1c from baseline to end of treatment. Other endpoints included FPG, 2 h postprandial plasma glucose (PPG) in a meal tolerance test (MTT), and body weight. Drug safety was also assessed., Trial Registration: Japan Pharmaceutical Information Center (identifier: JapicCTI-090908)., Results: Changes in HbA1c from baseline to end of treatment were -0.36, -0.62, and -0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus +0.06% in the placebo group (all P < 0.001). The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups (all P < 0.01) without increases in insulin levels from baseline. Luseogliflozin reduced body weight at all doses. There were no significant differences in the incidences of adverse events among groups. Most adverse events were mild in severity. There were no serious adverse events., Conclusions: Although this was a small-scale study with a short duration, all tested doses of luseogliflozin significantly improved glycemic control, reduced body weight, and were well tolerated in Japanese T2DM patients over the 12-week treatment period.

Objectives: Luseogliflozin is a selective sodium glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). This phase II study was conducted to confirm the efficacy and safety of luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with T2DM., Patients and Methods: Patients with hemoglobin A1c (HbA1c) of 6.9-10.5% on diet therapy were randomized in a double-blind manner to treatment with 1, 2.5, 5, or 10 mg luseogliflozin or placebo for 12 weeks (n = 56, 56, 54, 58, and 58, respectively)., Trial Registration: Japan Pharmaceutical Information Center (identifier: Japic CTI-101191)., Main Outcome Measures: The primary endpoint was the change in HbA1c from baseline to the end of treatment. Other endpoints included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight. Adverse events were recorded throughout the study., Results: HbA1c decreased significantly at the end of treatment in the 1, 2.5, 5, and 10 mg luseogliflozin groups compared with placebo (-0.29, -0.39, -0.46, and -0.43%, respectively, versus +0.22%; all P < 0.001), as did FPG and PPG (all P < 0.001). Body weight also decreased significantly in all luseogliflozin groups compared with placebo (all P < 0.001). The incidence rates of adverse events (40.0-50.0%) were not significantly different among the five groups. The overall incidence of hypoglycemia was low. Limitations of this study include the short study duration and the relatively small sample size., Conclusions: In Japanese patients with T2DM, luseogliflozin was well tolerated, improved glycemic control, and reduced body weight over 12 weeks of treatment at all tested doses. Doses of ≥2.5 mg achieved similar improvements in glycemic control.

Objective: Luseogliflozin--a novel, orally bioavailable, 1-thio-D-glucitol derivative and a selective sodium glucose cotransporter 2 inhibitor--has shown efficacy and tolerability in previous phase 2 studies. This phase 3, randomized, double-blind, placebo-controlled, comparative study aimed to confirm the superiority of 24 week luseogliflozin 2.5 mg monotherapy over placebo in reducing hemoglobin A1c (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM)., Methods: Patients with HbA1c levels of 6.9%-10.5% were randomized to receive luseogliflozin 2.5 mg or placebo once daily for 24 weeks (n = 79 in each group). The primary endpoint was change from baseline in HbA1c at end of treatment. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) following a meal tolerance test, body weight, and abdominal circumference. Safety assessments included adverse events (AEs), clinical laboratory tests, and vital signs., Results: At the end of treatment, HbA1c was significantly decreased from baseline in the luseogliflozin 2.5 mg group (-0.63%) versus the placebo group (0.13%), with a between-group difference of -0.75% (p < 0.001). Additionally, significant reductions in FPG, PPG, body weight, and abdominal circumference were noted with luseogliflozin compared with placebo (all p < 0.05). Luseogliflozin was well tolerated; there was no significant difference between groups in the incidence of AEs (luseogliflozin, 59.5%; placebo, 57.0%). No AEs led to study drug discontinuation. Most AEs were mild in severity, with no severe AE reported. Limitations of this study include its short study duration and small sample size., Conclusion: Luseogliflozin monotherapy for 24 weeks was superior to placebo in reducing HbA1c levels. It also reduced FPG, PPG, body weight, and abdominal circumference and was well tolerated in Japanese patients with T2DM., Clinical Trial Registration: JapicCTI-111661.

Luseogliflozin [Lusefi(®) (Japan)] is an orally active second-generation sodium-glucose co-transporter 2 (SGLT2) inhibitor developed by Taisho Pharmaceutical for the treatment of patients with type 2 diabetes mellitus (T2DM). The drug has received its first global approval for this indication in Japan, either as monotherapy or in combination with other antihyperglycaemic agents. This article summarises the milestones in the development of luseogliflozin leading to this first approval for the treatment of T2DM.

Purpose: The purpose of this study was to assess the efficacy of supervised tooth-brushing with xylitol toothpaste to prevent early childhood caries (ECC) and reduce mutans streptococci., Methods: In this cluster-randomized efficacy trial, 196 four- to five-year-old children in four Head Start classrooms in the Marshall Islands were randomly assigned to supervised toothbrushing with 1,400 ppm/31 percent fluoride xylitol or 1,450 ppm fluoride sorbitol toothpaste. We hypothesized that there would be no difference in efficacy between the two types of toothpaste. The primary outcome was the surface-level primary molar caries increment (d(2-3)mfs) after six months. A single examiner was blinded to classroom assignments. Two classrooms were assigned to the fluoride-xylitol group (85 children), and two classrooms were assigned to the fluoride-sorbitol group (83 children). The child-level analyses accounted for clustering., Results: There was no difference between the two groups in baseline or end-of-trial mean d(2-3)mfs. The mean d(2-3)mfs increment was greater in the fluoride-xylitol group compared to the fluoride-sorbitol group (2.5 and 1.4 d(2-3)mfs, respectively), but the difference was not significant (95% confidence interval: -0.17, 2.37; P=.07). No adverse effects were reported., Conclusion: After six months, brushing with a low-strength xylitol/fluoride tooth-paste is no more efficacious in reducing ECC than a fluoride-only toothpaste in a high caries-risk child population.

Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.

Objective: The aim of this study was to test the efficacy of long-term, daily intake of erythritol and xylitol candy, compared with sorbitol candy, on the development of enamel and dentin caries lesions., Methods: The study was a double-blind randomized controlled prospective clinical trial. Altogether 485 primary school children, first- and second-graders at baseline, from southeastern Estonia participated in this 3-year intervention. Each child consumed four erythritol, xylitol or sorbitol (control) candies three times per school day. The daily intake of polyol was about 7.5 g. The International Caries Detection and Assessment System (ICDAS) was used in the clinical examinations by four calibrated examiners at baseline and at 12, 24 and 36 months., Results: The annual examination analyses and the follow-up analyses confirmed that the number of dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months follow-up was significantly lower in the mixed dentition in the erythritol group than in the xylitol or control group. Time of enamel/dentin caries lesions to develop and of dentin caries lesions to progress was significantly longer in the erythritol group compared to the sorbitol and xylitol groups. Also the increase in caries score was lower in the erythritol group than in the other groups., Conclusions: In the follow-up examinations, a lower number of dentin caries teeth and surfaces was found in the erythritol group than in the xylitol or control groups. Time to the development of caries lesions was longest in the erythritol group., Trial Registration: ClinicalTrials.gov Identifier NCT01062633., (© 2014 S. Karger AG, Basel.)

Modafinil is a wake-promoting drug and has been approved for the treatment of excessive daytime sleepiness in narcolepsy and obstructive sleep apnea. Modafinil was shown to improve learning and memory in rodents, and to reverse memory deficits induced by sleep deprivation or stress. However, depending on the memory paradigm used, modafinil might also impair memory. We aimed to investigate the effects of modafinil on memory consolidation and retrieval for object recognition and inhibitory avoidance in naïve adult rats. We also investigated whether acute or chronic administration of modafinil would reverse memory deficits induced by iron overload, a model of memory impairment related to neurodegenerative disorders. Adult naïve rats received modafinil (0.0, 0.75, 7.5 or 75 mg/kg) either immediately after training or 1 h prior to testing in object recognition or inhibitory avoidance. Iron-treated rats received modafinil immediately after training in object recognition. In order to investigate the effects of chronic modafinil, iron-treated rats received daily injections of modafinil for 17 days, and 24 h later they were trained in object recognition or inhibitory avoidance. Acute modafinil does not affect memory consolidation or retrieval in naive rats. A single injection of modafinil at the highest dose was able to recover recognition memory in iron-treated rats. Chronic modafinil completely recovered iron-induced recognition memory and emotional memory deficits. Additional preclinical and clinical studies are necessary in order to support the applicability of modafinil in recovering memory impairment associated with neurodegenerative disorders., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study examined the effect of long-term control of hyperglycemia with a new sodium glucose cotransporter 2 inhibitor, luseogliflozin, given alone or in combination with lisinopril on the progression of renal injury in the T2DN rat model of type 2 diabetic nephropathy. Chronic treatment with luseogliflozin (10 mg/kg/day) produced a sustained increase in glucose excretion and normalized blood glucose and glycosylated hemoglobin levels to the same level as seen in the rats treated with insulin. It had no effect on blood pressure. In contrast, lisinopril (10 mg/kg/day) reduced mean blood pressure from 140 to 113 mmHg. Combination therapy significantly reduced blood pressure more than that seen in the rats treated with lisinopril. T2DN rats treated with vehicle exhibited progressive proteinuria, a decline in glomerular filtration rate (GFR), focal glomerulosclerosis, renal fibrosis, and tubular necrosis. Control of hyperglycemia with luseogliflozin prevented the fall in GFR and reduced the degree of glomerular injury, renal fibrosis, and tubular necrosis. In contrast, control of hyperglycemia with insulin had no effect on the progression of renal disease in T2DN rats. Reducing blood pressure with lisinopril prevented the fall in GFR and reduced proteinuria and the degree of glomerular injury and tubular necrosis. Combination therapy reduced the degree of glomerular injury, renal fibrosis, and tubular necrosis to a greater extent than administration of either drug alone. These results suggest that control of hyperglycemia with luseogliflozin slows the progression of diabetic nephropathy more than that seen with insulin, and combination therapy is more renoprotective than administration of either compound alone.

Probiotic bifidobacteria are widely used in the prevention of childhood diseases. These bacteria are also associated with caries occurrence. The present secondary analysis in a low-caries population evaluated the effect of early administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on caries occurrence and identified markers of dental decay in early childhood. In the original randomized, double-blind, placebo-controlled study (NCT00638677, http://www.clinicaltrials.gov), infants (n = 106) received BB-12, xylitol or sorbitol tablets from the age of 1-2 months to 2 years with a slow-release pacifier or a spoon (daily dose of BB-12 10(10) colony-forming units, polyol 200-600 mg). The present data were collected using clinical examinations and questionnaires at the age of 4 years. The occurrence of dental caries was assessed using the International Caries Detection and Assessment System. Oral hygiene status and mutans streptococci (MS) levels were also determined. No differences were detected between the study groups in the occurrence of enamel caries (p = 0.268) or obvious dentinal caries (p = 0.201). The occurrence of caries was associated with daily consumption of sweet drinks (p = 0.028), visible plaque observed (p = 0.002) and MS detected in the dental plaque (p = 0.002). Administration of BB-12 in infancy does not seem to increase or decrease the occurrence of caries by 4 years of age in a low-caries population., (Copyright © 2013 S. Karger AG, Basel.)

Aim: To evaluate the long-term outcome of a mother-child project in which mothers (n=173) with high counts of salivary mutans streptococci were randomly assigned to daily chewing gums containing xylitol (A), chlorhexidine/ xylitol/sorbitol (B), or sodium fluoride/xylitol/sorbitol (C) for one year, when the child was between 6 and 18 months., Methods: 140 of the off-springs were re-examined at the age of 10 years and 204 children of mothers with low counts of salivary mutans streptococci three months after delivery served as positive controls (D). Caries was scored in the young permanent dentition on enamel (noncavitated) and dentine (cavitated) levels., Results: The long-term attrition rate was 15%. The overall caries prevalence in the combined groups at 10 years of age was 31% (21% non-cavitated; 17% cavitated) with a mean DS of 0.7 (SD 1.3). No significant differences were found between the three experimental groups (A-C), or when compared with the control group. A statistically significant (p<0.05) positive relationship between the levels of salivary mutans streptococci at 18 months of age and the caries experience at the age of 10 years was disclosed for all groups combined., Conclusion: No beneficial longterm effects of maternal xylitol gum exposure on their children's dental health were demonstrated when compared with gums containing chlorhexidine and fluoride.

Aim: Pityriasis alba (PA) is a skin disorder characterized by finely scaly, hypopigmented patches, typical of childhood, that also represents an atopic dermatitis (AD) minor sign according to Hanifin and Rajka criteria. It may be isolated or associated with AD representing, sometimes an atypical manifestation of AD during the long-term follow-up of the disease. Aim of the study was to evaluate of the efficacy and tolerability of AR-GG27® (sorbityl furfural palmitate) cream in the treatment of childhood mild or moderate AD associated with PA., Methods: The trial is a single center, double-blind, randomized, placebo-controlled study. The study included patients of both sexes, aged between two months and 15 years, suffering from mild and moderate AD always associated with PA. Xerosis was present in all patients. The treatment with topical steroids or topical calcineurin inhibitors (TIMs) had to be suspended for at least 15 days. Any systemic therapy and phototherapy or sun exposure were withdrawn at least 30 days before. Emollients were stopped at least seven days before. During the trial, no other local or systemic treatments were allowed, as well as sun exposure. Patients affected by AD with viral, bacterial or fungal overinfection or patients with diabetes mellitus, severe systemic diseases or intolerance to one or more components of the product were excluded. The primary endpoint was the evaluation of the average change in the Investigator Global Assessment (IGA) after 15 and 30 days of treatment. The second endpoint was the evaluation of severity of three different clinical signs: erythema, excoriation desquamation, using a subjective five-point scale. Changes in pruritus severity was also considered during the entire period of treatment, through the use of a Visual Analogue Scale (VAS). A P<0.05, two tailed was considered as statistically significant., Results: After 15 and 30 days there was a statistically significant difference in the group treated with AR-GG27®, compared to the placebo (respectively, P=0.0007 and P=0.005). After 15 days of treatment, itching was clearly reduced in AR-GG27® treated group compared with the placebo, both in the study population (P=0.01) and in patients where the symptom was present from the beginning (P=0.05)., Conclusion: AR-GG27® showed a beneficial action associated with high compliance and tolerability in dermatological skin conditions characterized by inflammation and tissue oxidative stress in children, as PA with mild and moderate AD.

Objectives: This study aimed to appraise, within the context of tooth caries, the current clinical evidence and its risk for bias regarding the effects of xylitol in comparison with sorbitol., Methods: Databases were searched for clinical trials to 19 March 2011. Inclusion criteria required studies to: test a caries-related primary outcome; compare the effects of xylitol with those of sorbitol; describe a clinical trial with two or more arms, and utilise a prospective study design. Articles were excluded if they did not report computable data or did not follow up test and control groups in the same way. Individual dichotomous and continuous datasets were extracted from accepted articles. Selection and performance/detection bias were assessed. Sensitivity analysis was used to investigate attrition bias. Egger's regression and funnel plotting were used to investigate risk for publication bias., Results: Nine articles were identified. Of these, eight were accepted and one was excluded. Ten continuous and eight dichotomous datasets were extracted. Because of high clinical heterogeneity, no meta-analysis was performed. Most of the datasets favoured xylitol, but this was not consistent. The accepted trials may be limited by selection bias. Results of the sensitivity analysis indicate a high risk for attrition bias. The funnel plot and Egger's regression results suggest a low publication bias risk. External fluoride exposure and stimulated saliva flow may have confounded the measured anticariogenic effect of xylitol., Conclusions: The evidence identified in support of xylitol over sorbitol is contradictory, is at high risk for selection and attrition bias and may be limited by confounder effects. Future high-quality randomised controlled trials are needed to show whether xylitol has a greater anticariogenic effect than sorbitol., (© 2012 FDI World Dental Federation.)

A randomized clinical trial studied the effects of early administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on oral colonization of (1) mutans streptococci (MS), and (2) BB-12. In this double-blind, placebo-controlled study, infants (n = 106) received probiotic bacteria (BB-12 group), xylitol (X group), or sorbitol (S group). Test tablets were administered twice a day (from the age of 1-2 months) with a novel slow-release pacifier or a spoon (daily dose of BB-12 10(10) CFU, polyol 200-600 mg). Samples were collected from mucosa/teeth at the age of 8 months and 2 years for BB- 12 determination (qPCR) and plate culturing of MS (MSB, TYCSB), lactobacilli (Rogosa) and yeasts (Sabouraud). The MS levels of the mothers were determined (Dentocult SM Strip Mutans). The baseline characteristics of the three groups were similar. Mean duration of tablet delivery was 14.9 ± 6.7 months. In all groups, >90% of the mothers showed high MS counts (log CFU ≥5). MS colonization percentages of the children at the age of 2 years were rather low (BB-12 group: 6%; X group: 31%; S group: 10%; p < 0.05). The levels of lactobacilli and yeasts did not differ between the groups. BB-12 cell counts barely exceeding the detection limit were found in three of the oral samples of the 8-month-old children; however, the 2-year samples did not contain BB-12. The early administration of BB-12 did not result in permanent oral colonization of this probiotic or significantly affect MS colonization in the children., (Copyright © 2012 S. Karger AG, Basel.)

The activity of complex preparation Sorbilact was studied up in the patients, suffering obturative jaundice after surgical interventions on hepatopancreatoduodenal zone organs. Preparation Sorbilact causes antishock, proenergetic, desintoxication, diuretic and procinetic intestinal effects. The Sorbilact inclusion in complex of postoperative treatment of patients secures possibility of early administration of the enteral probe nutrition, promotes the trophic state optimization as well as the rehabilitation period duration shortening.

Aim: Management of functional dyspepsia is still controversial. Different controlled trials reported a superiority of prokinetics, H2-receptor antagonists and proton-pump inhibitors over placebo; nevertheless, symptomatic improvement after therapy is often incomplete and some of these drugs possess serious side effects. The aim of the study was to evaluate the efficacy of a new medical device in respect to domperidone in patients with functional dyspepsia., Methods: In a cross-over, randomized trial, 36 patients with functional dyspepsia ingested two daily doses of a medical device (Digerfast) or domperidone (Peridon) for 21 days. Clinical evaluation was performed at baseline (T0) and after 21 days (T1) for each treatment. A Visual Analogue Scale (VAS) and the generic scale 36-item Short Form (SF-36) were used to assess symptom intensity and changes in health-related quality of life, respectively., Results: At T0 no statistical difference was found for each symptom between medical device and domperidone. At T1 both treatments significantly improved in respect to baseline values all the evaluated gastrointestinal symptoms (P<0.5 for all comparisons) except for vomiting. No difference in gastrointestinal symptoms between the two treatments was found at T1. Regarding SF-36 evaluation, at T0 no statistical differences were found for each SF-36 parameter between the two regimens. At T1 both treatments significantly improved most of the evaluated SF-36 parameters in respect to baseline values. No difference in SF-36 parameters between the two treatments was found at T1., Conclusion: Both the medical device and domperidone significantly improved gastrointestinal symptoms and quality of life in subjects with functional dyspepsia, not showing significant difference in efficacy.

Objective: To compare the efficacy, tolerability and compliance of oral iron preparations (iron edetate and iron polymaltose complex) with each other and with intramuscular iron sorbitol in iron deficiency anaemia in children., Methods: A Randomized Controlled Trial (RCT) was carried out at the Paediatric Department of Combined Military Hospital (CMH) from January 2006 to December 2007. In total 146 children, up to 12 years age having haemoglobin (Hb%) less than 8 gm% were included. They were randomly distributed into three groups. Group A (64 cases) received oral sodium iron edetate (SIE), Group B (40 cases) received oral iron polymaltose complex (IPC) and group C (42cases) received intramuscular iron sorbitol (IS) in recommended dosages. Rise in Hb% > 10gm% was kept as desired target. Maximum duration of treatment planned was 2 weeks for parenteral iron (group C) and 12 weeks for oral iron (groups A and B). Haematological parameters- Hb%, mean corpuscular volum (MCV), mean corpuscuar haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) were measured at induction followed at 2 weeks, 4 weeks, 8 weeks and 12 weeks after start of treatment. Compliance and drop out rates were determined on each visit. Data was analyzed using SPSS version10.ANOVA was used to analyze difference in rise in Hb% at various intervals., Results: Statistically significant increase in mean Hb%, MCV, MCHC after 02 weeks was observed in group C (IS). Rise in these parametes became significant in group A (SIE) and B (IPC) after 04 weeks. Peristent rise was observed in oral groups at 08 and 12 weeks. Rise in Hb% was much faster in group C (IS). It took 2 weeks to achieve mean Hb% > 10gm% and compliance rate was 40.5%, while to achieve same target, duration required was 8 weeks in group A (SIE) and 12 weeks in group B (IPC) and compliance rate was 39% and 30% respectively. Adverse effects were much more common with group A (SIE) as compared to other two groups., Conclusion: Intramuscular iron sorbitol is a reliable and faster alternative modality for treatment of iron deficiency anaemia in children. Short duration of treatment, sure rise in Hb% and minimal adverse effects improve compliance as compared to oral preparations. Among oral preparations, rise in Hb% is more rapid with iron edetae. While IPC gives relatively slower rise in Hb% but side effects are much less as compared to SIE.

The authors previously reported that costunolide, an active compound isolated from the stem bark of Magnolia sieboldii, induced apoptosis via reactive oxygen species (ROS) and Bcl-2-dependent mitochondrial permeability transition in human leukemia cells. In the present study, the authors investigated whether mitogen-activated protein kinases (MAPKs) are involved in the costunolide-induced apoptosis in human promonocytic leukemia U937 cells. Treatment with costunolide resulted in the significant activation of c-Jun N-terminal kinase (JNK), but not of extracellular-signal-related kinase (ERK1/2) or p38. In vitro kinase assays showed that JNK activity was low in untreated cells but increased dramatically after 30 min of costunolide treatment. U937 cells co-treated with costunolide and sorbitol, a JNK activator, exhibited higher levels of cell death. In addition, inhibition of the JNK pathway using a dominant-negative mutation of c-jun and JNK inhibitor SP600125, significantly prevented costunolide-induced apoptosis. Furthermore, pretreatment with the antioxidant NAC (N-acetyl-L-cysteine) blocked the costunolide-stimulated activation of JNK while the overexpression of Bcl-2 failed to reverse JNK activation. Pretreatment with SP600125 recovered the costunolide-suppressed Bcl-2 expression. These results indicate that costunolide-induced JNK activation acts downstream of ROS but upstream of Bcl-2, and suggest that ROS-mediated JNK activation plays a key role in costunolide-induced apoptosis. Moreover, the administration of costunolide (intraperitoneally once a day for 7 d) significantly suppressed tumor growth and increased survival in 3LL Lewis lung carcinoma-bearing model.

Objectives: To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries among very young children and to evaluate the effect of xylitol in reducing acute otitis media in a subsequent study., Design: Double-blind randomized controlled trial., Setting: Communities in the Republic of the Marshall Islands., Participants: One hundred eight children aged 9 to 15 months were screened, and 100 were enrolled. Intervention Children were randomized to receive xylitol topical oral syrup (administered by their parents) twice a day (2 xylitol [4.00-g] doses and 1 sorbitol dose) (Xyl-2 x group) or thrice per day (3 xylitol [2.67-g] doses) (Xyl-3x group) vs a control syrup (1 xylitol [2.67-g] dose and 2 sorbitol doses) (control group)., Main Outcome Measures: The primary outcome end point of the study was the number of decayed primary teeth. A secondary outcome end point was the incidence of acute otitis media for reporting in a subsequent report., Results: Ninety-four children (mean [SD] age, 15.0 [2.7] months at randomization) with at least 1 follow-up examination were included in the intent-to-treat analysis. The mean (SD) follow-up period was 10.5 (2.2) months. Fifteen of 29 of the children in the control group (51.7%) had tooth decay compared with 13 of 32 children in the Xyl-3x group (40.6%) and eight of 33 children in the Xyl-2x group (24.2%). The mean (SD) numbers of decayed teeth were 1.9 (2.4) in the control group, 1.0 (1.4) in the Xyl-3x group, and 0.6 (1.1) in the Xyl-2x group. Compared with the control group, there were significantly fewer decayed teeth in the Xyl-2x group (relative risk, 0.30; 95% confidence interval, 0.13-0.66; P = .003) and in the Xyl-3x group (0.50; 0.26-0.96; P = .04). No statistical difference was noted between the 2 xylitol treatment groups (P = .22)., Conclusion: Xylitol oral syrup administered topically 2 or 3 times daily at a total daily dose of 8 g was effective in preventing early childhood caries.

Purpose: The purpose of this study was to examine the effects of xylitol gum (XG) on the acquisition pattern of 39 bacterial species, including mutans streptococci (MS), in infants., Methods: Ninety-seven mothers (MS counts > 10(5) CFU/ml) were randomly divided into 4 groups and received: (1) XG (4.2 gm/day); (2) XG (6 months after baseline exams); (3) sorbitol gum (4.2 gm/day); or (4) no gum. Groups 1 and 3 chewed gum 3 times a day for 9 months. Microbiota of plaque and saliva samples from the mother-child pairs were analyzed by culturing and via checkerboard DNA-DNA hybridization., Results: MS was isolated from 33% of the predentate infant (< or =5 months old) baseline saliva samples and from 41% of the saliva and 65% of the plaque samples at the final visit. At baseline, positive responses to "mother's checking of baby's food temperature using baby's spoon" and "starting a bottle after stopping breast-feeding" were significant predictors (P = .009 and P < .001, respectively) of infant's total streptococci counts. At the final visit (9 months later), there were no significant differences between treatment groups for infants' 39 microbial plaque species, including MS., Conclusions: Maternal use of xylitol gum did not result in statistically significant differences in the microbial plaque composition of 9- to 14-month-old infants.

Objective: To evaluate the in vivo potential of xylitol to reduce plaque acidogenicity in comparison to sorbitol., Method and Materials: After completing a questionnaire on general health, smoking, diet, and oral hygiene habits, 61 dentate adults refrained from oral hygiene for 3 days before the clinical baseline examination, which included decayed, missing, and filled teeth (DMFT) index, mutans streptococci and lactobacilli counts, and plaque acidogenicity (cH) index after a sucrose rinse. Then the participants were randomly allocated to consume either sorbitol or xylitol lozenges (5 pieces/day, 2 g each) for 4 weeks and were asked to refrain from oral hygiene for the 3 days prior to the final examination (cH, area < pH 7, bacterial counts)., Results: The variation of acidogenicity in different individuals was considerable at baseline (range: 0.2 to 446.6 min micromol/L) with a mean value of 37.9 +/- 58.9 min micromol/L for the sorbitol group and 60.6 +/- 87.6 min micromol/L for the xylitol group. At the end of the study, the reduction in the xylitol group (42.9 +/- 80.6 min micromol/L) was statistically significantly higher than in the sorbitol group (6.0 +/- 69.4 min micromol/L, P = .034), which was also confirmed in an additional analysis excluding 2 participants with extreme values (reduction for xylitol: 29.5 +/- 36.9 min micromol/L; sorbitol: 1.7 +/- 57.0 min micromol/L; P = .019). Statistically significant differences were also found for the area below pH 7 (reduction for xylitol: 10.8 min pH; sorbitol, 0.2 min pH; P = .0025)., Conclusion: The regular consumption of xylitol lozenges modifies dental plaque, resulting in a marked reduction in the plaque acidogenicity, which could not be detected using sorbitol lozenges. Therefore, xylitol could have an additional benefit in caries prevention.

The authors have studied influence of infusion of 800 ml RHEOSORBILACTUM, 500 ml VENOFUNDIN and 800 ml of 0,9% isotonic solution of sodium chloride with speed of 50-55 ml/mines on hemostasis, the maintenance of a liquid in the thorax, hemodynamic parameters in 60 patients with traumatic shock. It was revealed that the use of investigated volume of RHEOSORBILACTUM increases reliably (P<0,05) oxygen delivery for the account of the expressed haemodynamic effect which duration is less than during the use of VENOFUNDIN. It was revealed also that RHEOSORBILACTUM increases reliably (P<0,05) quantity of liquid in the thorax without an considerable difference with other investigated medications. There was no influence of RHEOSORBILACTUM on time of trombus formation tests--prothrombin time, the international normalized index, activated partial thromboplastin time.

Background: The authors conducted a systematic review of original studies that was designed to assess the impact of polyol-containing chewing gum on dental caries compared with the effect with no chewing gum., Review Methods: The authors searched MEDLINE, The Cochrane Library and Google Scholar up to May 2008 to identify peer-reviewed articles that compared polyol-containing chewing gum with no chewing gum. The authors extracted study characteristics, data on incremental dental caries and quality by consensus. Data on prevented fraction (PF) were pooled across studies., Results: The results of 19 articles with data from 14 study populations showed that the use of xylitol, xylitol-sorbitol blend and sorbitol were associated with mean PF (95 percent confidence interval) of 58.66 percent (35.42-81.90), 52.82 percent (39.64-66.00) and 20.01 percent (12.74-27.27), respectively. For the sorbitol-mannitol blend, it was 10.71 percent (-20.50-41.93), which was not statistically significant. Sensitivity analyses confirmed the robustness of the findings., Clinical Implications: Although research gaps exist, particularly on optimal dosing and relative polyol efficacy, research evidence supports using polyol-containing chewing gum as part of normal oral hygiene to prevent dental caries.

Objective: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery., Methods: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the (2)H(2)-glucose method. Muscle microdialysis., Clinical Data: maximal daily T degrees, intensive care unit (ICU) and hospital stay., Results: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P=0.09). After FO, a trend toward shorter ICU stay (1.6+/-0.4 versus 2.3+/-0.4), and hospital stay (9.9+/-2.4 versus 11.3+/-2.7 days: P=0.19) was observed., Conclusions: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.

Clinical efficacy of preparation Lactoprotein with sorbitol (manufactured by CSS "Biopharma", Ukraine) in patients with deep burns was studied up. High efficacy of the preparation in the stage of the burn shock was established, including the antishock action, the endogenous intoxication severity reduction and metabolic acidosis prophylaxis.

Background: The multiple functions of saliva play a significant role in the prevention of dental caries., Methods: Chewing gum is known to stimulate salivary flow, and the results of studies of the role of stimulated saliva in the oral clearance of food particles, neutralization of dental plaque acids and reduction of the incidence of dental caries have been reported. The author reviews the results of these clinical caries trials., Results: Seven clinical trials have evaluated the impact of chewing gum on caries incidence. These studies have shown that chewing sugar-free gum after meals results in a significant decrease in the incidence of dental caries and that the benefit is due to stimulating salivary flow rather than any chewing gum ingredient., Conclusions: Stimulating salivary flow through the chewing of sugar-free gum after meals has been shown to reduce the incidence of dental caries., Clinical Implications: Practical measures for stimulating salivary flow after meals or snacks should be considered in caries prevention programs.

The aim was to evaluate the effect of xylitol and probiotic chewing gums on salivary mutans streptococci (MS) and lactobacilli (LB). The material consisted of 80 healthy young adults (21-24 years) who volunteered after informed consent. They were assigned by random into one of four parallel study groups: A, probiotic gum group; B, xylitol gum group; C, probiotic + xylitol gum group; and D, placebo gum group. The gums were taken three times daily after meals, and the intervention period was 3 weeks. The probiotic gums contained two strains of Lactobacilli reuteri (ATCC 55730 at a dose of 1 x 10(8) CFU/gum and ATCC PTA 5289 at a dose of 1 x 10(8) CFU/gum), and each pellet of the xylitol gum contained approximately 1.0 g xylitol as single sweetener. Pretreatment and posttreatment samples of stimulated whole saliva were collected and quantified for MS and LB with chair-side kits. A statistically significant reduction (p < 0.05) of salivary MS was displayed in group A and B after the intervention when compared with baseline. A similar but nonsignificant tendency was seen in group C. No alterations of salivary LB was demonstrated in any group. In conclusion, daily chewing on gums containing probiotic bacteria or xylitol reduced the levels of salivary MS in a significant way. However, a combination of probiotic and xylitol gums did not seem to enhance this effect.

Dofetilide, a class III antiarrhythmic agent, is prescribed for conversion to and maintenance of normal sinus rhythm in patients with persistent atrial fibrillation or atrial flutter. Most antiarrhythmics have significant toxicities such as torsade de pointes, and patients should be closely monitored while receiving antiarrhythmic therapy. However, we know of no reports concerning management of intentional overdose of dofetilide that have been published. We report the case of a 33-year-old man who was treated for ingestion of approximately 5 mg of dofetilide as a suicide attempt. In addition, he had a known history of cocaine abuse. He came to the emergency department approximately 45 minutes after the ingestion; examination revealed a QTc interval of approximately 570 msec. He was treated with activated charcoal and sorbitol by nasogastric tube and received aggressive supplementation with potassium and magnesium. The patient was monitored by telemetry for several days and responded well. Cardiac toxicity is the utmost concern when treating dofetilide overdose. The mainstay of treatment focuses on supportive care and prevention of drug absorption. Ventricular dysrhythmias or torsade de pointes should be treated according to advanced cardiac life support guidelines.

The aim of this study was to evaluate the effect of a new prophylactic gel on plaque pH and plaque fluoride concentration. Twelve participants with normal (n=6, >or=0.7 ml/min) and low (n=6, <0.7 ml/min) stimulated whole salivary secretion rate were included. After 3 days of plaque accumulation, at random the participants were (1) treated with Profylin fluoride gel with buffering components (active gel), (2) treated with Profylin fluoride gel without buffering components (placebo gel), (3) asked to rinse with water, and (4) given no treatment. All test series were followed by rinsing with a nutrition solution; after which registration of plaque pH was performed during 60 min. There were two drop outs with low salivary secretion rate in the water session. The overall least pronounced pH fall was found after the use of the prophylactic gel. Significant differences between the prophylactic gel and the placebo gel were found for the participants with normal secretion rate. Fluoride plaque concentrations evaluated in 12 individuals after (1) application of the active gel, (2) rinsing with 0.2% NaF, and (3) rinsing with water showed significantly higher values after rinsing with the NaF solution. It can be concluded that application of the active gel, particularly in subjects with normal salivary secretion rate, in general, buffered plaque pH to higher levels. Factors like concentration of buffering agent and solubility of the gel need to be further evaluated to improve the effect.

Introduction: Intravenous lipid is commonly used as part of total parenteral nutrition (TPN) in premature babies. The gold standard of measuring lipid tolerance involves measuring serum triglyceride levels. Many hospitals in Asia do not have this facility and rely on visual turbidity to titrate the rate of lipid infusion. The aim of this study was to determine if visual turbidity correlates with serum triglyceride levels., Materials and Methods: Twenty-seven samples were taken from 8 babies on intravenous (IV) lipid infusion for the analysis of serum triglyceride levels and visual turbidity (assessed by 2 senior neonatologists independently). Serum turbidity was classified either as clear or turbid. Lipid intolerance was defined as triglyceride levels greater than 200 mg/dL (2.25 mmol/L)., Results: Both neonatologists similarly classified 20 out of 27 specimens. Serum triglyceride levels for clear samples (n = 10) were significantly lower than those for turbid samples (n = 10) (P <0.01). The clear specimens all had normal serum triglyceride levels (mean, 1.16 mmol/L; range, 0.43 to 1.96). Not all turbid specimens had unacceptable serum triglyceride levels (mean, 2.37 mmol/L; range, 1.37 to 5.75). In the remaining 7 specimens, there was a difference in opinion regarding serum turbidity. The triglyceride levels for these 7 samples were all normal (mean, 1.17 mmol/L; range, 0.66 to 1.72)., Conclusion: Serum turbidity may be used as a screening tool in assessing lipid tolerance in babies on TPN as all clear samples had acceptable serum triglyceride level if we set the maximum cutoff at 2.25 mmol/L. Patients with turbid samples should ideally have their serum triglyceride taken to confirm lipid intolerance before altering their lipid infusion rate as they may have acceptable triglyceride levels.

Purpose: To evaluate the effects of porcine mucin- and carboxymethylcellulose-based (CMC) solutions on the inhibition of demineralization of pre-demineralized bovine enamel and dentin in vitro. Additionally the sugar substitutes sorbit or xylit were added to the various solutions., Methods: 54 enamel and dentin samples were prepared from 14 freshly extracted permanent bovine central incisors. The samples were demineralized (pH 5.0 for enamel and pH 5.5 for dentin; 14 days) and subsequently exposed to either mucin- or CMC-based solutions combined with xylit and sorbit at pH 5.5. After in vitro exposure, the specimens were cut perpendicular to the enamel/dentin surface and the sections were ground (4000 grit) to a uniform thickness (100 microm). Mineral loss and lesion depths were evaluated from microradiographs with a dedicated software package (TMR 2.0.27.2)., Results: For both dental hard tissues, storage in the mucin-containing solutions resulted in significantly higher lesion depths (deltaLD), but lower mineral loss values (deltadeltaZ) compared to the CMC-containing solutions (P< 0.05; 2-way ANOVA). For the dentin specimens, significant differences in deltadeltaZ were observed between sorbit and xylit (P< 0.05; 2-way ANOVA). The mineral loss and lesion depths of the enamel specimens did not differ significantly after storage in the various solutions (P> 0.05; Bonferroni post hoc test). For the dentin specimens stored in the solution containing mucin/xylit the mineral loss was significantly decreased compared to the other mucin groups as well as to the CMC/xylit solution (P< 0.05; Bonferroni post hoc test).

Objectives: To evaluate if sugar alcohols would reduce enamel demineralization enhancing the fluoride (F) effect., Methods: A crossover in situ study was conducted in four phases, during which 10 volunteers were submitted to one of the treatments: (I) Distilled and deionized water, as a negative control; (II) F (226 microg F/ml as NaF; concentration used in commercial mouthrinse); (III) X:S (xylitol:sorbitol 1:3; final concentration 1.6M; 28% of sugar alcohols) and (IV) F+X:S (same final concentration that groups II and III). The volunteers wore palatal appliances containing four bovine enamel blocks of known surface microhardness (SMH), covered with a 'test plaque' of mutans streptococci, which were immersed during 1 min in one of the allocated treatment solutions simultaneously that the volunteers rinsed their mouths with the same solution. After the rinsing the appliances were put in the mouth and after 20 min a cariogenic challenge was made with 20% sucrose solution during 1 min. After further 45 min the 'test plaque' was collected for F analysis, enamel SMH was again determined and the percentage of change in relation to baseline was calculated; F uptake in enamel was also determined., Results: With respect to all the analyses made, the group F+X:S did not differ from the F treatment (p>0.05) and the groups treated with F and F+X:S differed from the negative control (p<0.05)., Conclusions: The results suggest that xylitol:sorbitol may not enhance the effect of fluoride present in mouth rinse on the reduction of enamel demineralization.

Background: The author compared the caries-inhibitory action of sorbitol- and xylitol-sweetened chewing gum and assessed the role of these products in caries prevention., Types of Studies Reviewed: The author reviewed studies including randomized field trials with substantial numbers of participants and observational studies. He did not review case studies. He found studies through a MEDLINE search and by hand searching., Results: When compared with sugar-sweetened gum, sorbitol-sweetened gum had low cariogenicity [corrected] when it was chewed no more than three times per day. Xylitol-sweetened gum was noncariogenic in all of the protocols tested. Some studies claimed that xylitol-sweetened gum had an anticariogenic effect, though these claims need further study. There also is good evidence that when mothers of infants and young children chew xylitol-sweetened gum, it will block transmission of mutans streptococci from mother to child., Clinical Implications: The evidence is strong enough to support the regular use of xylitol-sweetened gum as a way to prevent caries, and it can be promoted as a public-health preventive measure. Chewing xylitol-sweetened gum, especially for patients who like chewing gum, can be fitted readily into a regimen that includes frequent fluoride exposure, good oral hygiene and regular dental appointments.