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.     

Influence of the physicochemical features of TiO2 nanoparticles on the formation of a protein corona and impact on cytotoxicity

Due to their unique properties TiO₂ nanoparticles are widely used. The adverse effects they may elicit are usually studied in relation to their physicochemical features. However, a factor is often neglected: the influence of the protein corona formed around nanoparticles upon contact with biological media. Indeed, although it is acknowledged that it can strongly influence nanoparticle toxicity, it is not systematically considered. The aim of this study was to characterize the formation of the protein corona of TiO₂ nanoparticles as a function of the main nanoparticle properties and investigate potential relationship with the cytotoxicity nanoparticles induce in vitro in human lung cells. To that purpose, five TiO₂ nanoparticles differing in size, shape, agglomeration state and surface charge were incubated in cell culture media (DMEM or RPMI supplemented with 10% fetal bovine serum) and the amount and profile of adsorbed proteins on each type of nanoparticle were compared to their toxicological profile. While nanoparticle size and surface charge were found to be determinant factors for protein corona formation, no clear impact of the shape and agglomeration state was observed. Furthermore, no clear relationship was evidenced between the protein corona of the nanoparticles and the adverse effect they elicited.

Characterization of the formation of the protein corona of TiO₂ nanoparticles as a function of the main nanoparticle properties and investigation of potential relationship with the cytotoxicity nanoparticles induce in vitro in human lung cells.     

The effect of alfuzosin on renal resistive index,urinary electrolytes and β2 microglobulin levels and TGF β-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction

Background: In this study, it was aimed to determine the effects of alfuzosin on experimentally generated unilateral partial ureteropelvic junction obstruction (UPO) in rats.

Materials and methods: Thirty Long–Evans rats were randomly allocated into five groups. In control group (C), nothing was performed; in group Sham (S) only laparotomy was done; in Alfuzosin group (A) only alfuzosin was administered for two weeks (10?mg/kg/day p.o.) without any surgery; in UPO group, unilateral UP junction obstruction was produced; and in the Group UPT (ureteropelvic obstruction?+?treatment), alfuzosin was administered for two weeks (10?mg/kg/day p.o.) in addition to UPO production. Renal pelvic anteroposterior diameters were determined with ultrasonography (USG) and renal arterial resistivity indexes by color Doppler USG. Urine was collected both at the beginning and at the end of the experiment for 24?h in all the groups and at the end of the experiment, blood samples were obtained. Blood and urine electrolytes and TGF-β1, urine density, urine β₂ microglobulin levels were determined. Renal tissue samples harvested from all of the rats were histopathologically evaluated. Results were determined using one-way ANOVA t-test; p?<?0.05 was accepted as significant.

Results: Urine density in the UPT group was lower with respect to UPO group and blood electrolytes were preserved as close to normal (p?<?0.05). In the UPT group, urine TGF-β1 and blood TGF-β1, blood β₂ microglobulin levels and histopathologic damage scores were lower compared to the UPO group (p?<?0.05).

Conclusion: It is shown in this experimental unilateral partial UPO model that alfuzosin treatment prevents obstructive renal damage.     

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.     

Risperidone,quetiapine and chlorpromazine may have induced priapism in an adolescent

Priapism is the prolonged, painful erection of penile tissue not accompanied by sexual arousal. Priapism has been established as a rare adverse drug reaction to drugs such as antipsychotics, psychostimulants, antidepressants, and mood stabilizers. Immediate intervention is needed to prevent destructive and irreversible complications, such as erectile dysfunction, disfigurement, inability of the penis to stay erect, and related social/emotional problems. Antipsychotic‐induced priapism may result from the alpha receptor occupancy property of those drugs. We report the case of a 13‐year‐old suffering from attention deficit–hyperactivity disorder plus conduct disorder with priapism related to antipsychotics. Episodes occurred with risperidone plus methylphenidate, quetiapine plus methylphenidate, and chlorpromazine alone.     

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.