Effects of cognitive remediation on cognitive and social functions in individuals with schizophrenia

ABSTRACT

Individuals with schizophrenia exhibit cognitive impairments, which are related to impairments in social functions. This study investigated the effects of cognitive remediation on cognitive, social, and daily living impairment. Participants were individuals with schizophrenia between 20 and 60 years old (N?=?44). Participants were randomly assigned to two groups: a cognitive remediation intervention group and a non-intervention control group. The control group was provided with conventional drug therapy and either day care or occupational therapy. The intervention group was provided with the “neuropsychological educational approach to cognitive remediation” developed by Medalia and co-workers. We assessed cognitive functions using the brief assessment of cognition in schizophrenia (BACS), and evaluated social and daily living functions using the global assessment of functioning (GAF) scale. Significant group by time interaction effects indicated that verbal memory, working memory, attention, and executive function showed significantly greater improvement at post-intervention for the intervention group than the control group. Social and daily living function also improved in the intervention group and improvements were maintained one year after intervention. These preliminary findings indicate that the combination of cognitive remediation and psychiatric rehabilitation is effective for facilitating improvements in cognitive function and social and daily living functions in individuals with schizophrenia.     

Increased prenatal blood manganese may induce gestational blood pressure

Objective: Pregnancy hypertension is the most common gestational complication and poses a critical risk for mother and fetus. Whether environmental factors may play an important role in disease occurrence is not fully determined. Methods: To investigate the effects of prenatal manganese (Mn) exposure on gestational blood pressure, 386 women were examined. Results: Early pregnancy blood Mn was significantly (p < 0.05) correlated with blood pressure through gestation. A significant association between odds of pre-hypertension with blood Mn was shown (OR:1.150, 95% CI:1.052–1.258). Conclusion: The current study results might suggest the blood Mn level during early stage of pregnancy as a potential risk factor for increasing the risk of gestational blood pressure.     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

     

Effects of Various Pharmaceutical Excipients on the Intestinal Transport and Absorption of Sulfasalazine,a Typical Substrate of Breast Cancer Resistance Protein Transporter

Breast cancer resistance protein (BCRP) transporter is an efflux transporter that utilizes energy from adenosine triphosphate hydrolysis to push its substrates, regardless of the concentration gradient. Its presence on the apical membrane of the intestinal mucosa is a major obstacle for the intestinal absorption of its substrates. In this study, we examined the effects of various pharmaceutical excipients on the intestinal transport and absorption of sulfasalazine, a BCRP substrate. Four excipients, including 0.05% and 0.075% BL-9EX, 0.01% and 0.05% Brij 97, 0.075% Labrasol, and 0.05% and 0.1% Tween 20 decreased the secretory transport of sulfasalazine in an in vitro diffusion chamber. Further investigation in an in situ closed loop experiment in rats showed that 0.05% and 0.1% BL-9EX and 0.1% Brij 97 effectively enhanced the intestinal absorption of sulfasalazine while maintaining minimal toxicity to the intestinal mucosa. However, 0.1% Brij 97 also increased the intestinal absorption of 5(6)-carboxyfluorescein, a paracellular marker compound. These findings suggest that BL-9EX might effectively inhibit the BCRP-mediated efflux of sulfasalazine in vivo, indicating that BL-9EX could improve the intestinal absorption of sulfasalazine and other BCRP substrates.     

Thirteen week toxicity study of dietary l‐tryptophan in rats with a recovery period of 5 weeks

Although l ‐tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l ‐tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague–Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l ‐tryptophan. Body weight gain and food consumption significantly decreased throughout the administration period in males in the 2.5% group and in both sexes in the 5.0% group. At the end of the dosing period, decreases in water intake in males in the 5.0% group and in serum glucose in females in the 5.0% group were observed. The changes described above were considered toxicologically significant; however, they were not observed after a 5 week recovery period, suggesting reversibility. Consequently, the no‐observed‐adverse‐effect level of l ‐tryptophan in the present study was 1.25% for males and 2.5% for females (mean intake of l ‐tryptophan: 779 mg kg^–1 body weight day^–1 [males] and 1765 mg kg^–1 body weight day^–1 [females]). As the basal diet used in this study contained 0.27% of proteinaceous l ‐tryptophan, the no‐observed‐adverse‐effect level of overall l ‐tryptophan was 1.52% for males and 2.77% for females (mean intake of overall l ‐tryptophan: 948 mg kg^–1 body weight day^–1 (males) and 1956 mg kg^–1 body weight day^–1 (females)). We conclude that l ‐tryptophan has a low toxicity profile in terms of human use.     

Traumatic unilateral temporomandibular joint dislocation overlooked for more than two decades

Forward dislocation of the temporomandibular joint commonly can be easily diagnosed and successfully reduced by manual repositioning. In this report, we discuss a rare case of prolonged temporomandibular dislocation that had persisted for more than 20 years because the otolaryngologist and dentist had missed the dislocation. This patient underwent open reduction and mandibular joint plasty with preoperative orthodontic therapy. It is possible that strong pain and mouth-closing disability may gradually remit and only deviated mandibular prognathism like malocclusion may persist. Therefore, abnormal occlusion warrants careful attention to temporomandibular joint dislocation.