Involvement of oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes

1.?Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown.

2.?In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p?<?0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate generators. Also, the present results demonstrated that CYP450 is involved in OLZ-induced oxidative stress and cytotoxicity mechanism.

3.?It is concluded that OLZ hepatotoxicity is associated with both mitochondrial/lysosomal involvement following the initiation of oxidative stress in hepatocytes.     

High prevalence of chronic hepatitis B infection among injection drug users in Iran: the need to increase vaccination of adults at risk

We measured the prevalence of HBV surface antigen (HBsAg) among male injection drug users (IDUs) in Detention, Tehran, Iran. A cross-sectional survey included 499 male IDUs arrested by police during a predetermined police sweep in Tehran (February, 2006). A questionnaire was filled out for each individual. Blood specimens were collected for HBsAg testing. Prevalence of HBsAg was 5.8% (95% CI 3.6-7.9). The majority of chronic HBV infections, 69.2%, were among adults age 25 to 34 years. The high prevalence of HBsAg highlights the need for special efforts to increase vaccination among adult populations at risk for HBV infection in order to reducing continuing transmission and stave off future high burden of disease.     

High incidence of autosomal recessive nonsyndromal congenital retinal nonattachment (NCRNA) in an Iranian founding population

In an isolated and founding Iranian population the prevalence of congenital total blindness is 1.1%. Clinical findings such as lack of perception of light, massive retrolental mass, shallow anterior chamber and nystagmus, in otherwise normal individuals, correspond to nonsyndromal congenital retinal nonattachment. To determine the inheritance of this disease we constructed an extensive nine-generation pedigree of the affected kindred living in the Iranian founding population. The pedigree, which includes 42 patients from 25 sibships, clearly suggests autosomal recessive inheritance. To verify the inheritance, we compared the average coefficient of inbreeding (F) of the affected sibships with that of the control sibships, calculated the patients' sex ratio, and also compared the observed relative frequency of the disease with its expected relative frequencies for different modes of inheritance. The patients' average F value is significantly greater than that of the controls (P < 0.001). The sex ratio of the patients is close to unity and the observed relative frequency of the disease is close to that of an autosomal recessive trait. All these findings strongly support autosomal recessive transmission of this disease. Am. J. Med. Genet. 78:226–232, 1998. © 1998 Wiley-Liss, Inc.     

Efficacy of Myrtus communis L. to Inactivate the Hydatid Cyst Protoscoleces

Purpose: The present study aims to investigate the scolicidal effects of Myrtus communis L. essential oil against protoscoleces of hydatid cysts and also its toxicity in mice model. Materials and Methods: Protoscoleces were aseptically aspirated from sheep livers having hydatid cysts. Various concentrations of the essential oil (12.5–100 μl/ml) were used for 5–30 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1% eosin staining). Moreover, 48 male NMRI mice were used to determine the acute and sub-acute toxicity of M. communis essential oil. One-way ANOVA with Tukey's post-hoc test was used to assess differences between experimental groups. Results: Findings of the present study demonstrated that the M. communis essential oil at the concentration of 100 μl/ml after 5 min of exposure killed 100% protoscoleces. Similarly, the mean mortality rate of protoscoleces after 10 min of exposure to concentration of 50 μl/ml was 100%. However, lower concentrations (12.5 and 25 μl/ml) of M. communis essential oil provoked a delayed protoscolicidal effects. The LD₅₀ values of intraperitoneal injection of the M. communis essential oil was 2.23 mL/kg body wt. No significant difference (p > .05) was observed in the clinical chemistry and hematological parameters following oral administrations of M. communis essential oil at the doses 0.05, 0.1, 0.2, and 0.4 mL/kg for 14 days. Conclusion: The results showed potent scolicidal activity of M. communis with no significant toxicity, which might be used as a natural scolicidal agent in hydatid cyst surgery.     

Role of chemokines in metastatic niche: new insights along with a diagnostic and prognostic approach

Chemokines are cytokines that are involved in the movement of leukocytes and the occurrence of immune responses. It has recently been noted that these cytokines play a role in the movement of cancer cells to different parts of the body and create a suitable environment [i.e. (pre) metastatic niche] for their growth and proliferation. We studied the role of chemokines in the metastasis of cancer cells, as well as their involvement in the proliferation and growth of these cells. Relevant literature was identified by a PubMed search (2005–2017) of English language papers using the terms ‘chemokine,’ ‘metastasis niche,’ and ‘organotropism.’ Based on the nature of cancer cells, the expression of chemokine receptors on these cells leads to metastasis to various organs, which ultimately causes changes in different signaling pathways. Finally, the targeting of chemokines on cancer cells could prevent the metastasis of cancer cells toward different organs.     

Femoral shaft fractures in childrenElastic stable intramedullary nailing in 31 cases

We report our experience with elastic stable intramedullary titanium nailing (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31 children (20 boys), median age 6 (4–11) years, with ESIN for 29 closed and 2 grade I open femoral shaft fractures. We reviewed 30 children clinically after median 1.5 (1–3) years. Their median hospital stay was 6 (2–20) days. All fractures were radiographically united at a median of 7 (5–9) weeks. The nails were removed in 29 children after a median of 22 (6–38) weeks postoperatively. At follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10 degrees of internal rotational deformity in 1 child. No angular deformity had occurred. Elastic stable intramedullary nailing seems to be a safe method for the treatment of femoral shaft fractures in children between 4 and 11 years of age.     

Preparation and In vitro Evaluation of Naproxen Suppositories

The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository.