Reduced tumor growth in vivo and increased c-Abl activity in PC3 prostate cancer cells overexpressing the Shb adapter protein

Background  

Induction of apoptosis is one strategy for treatment of prostate cancer. The Shb adapter protein has been found to regulate apoptosis in various cell types and consequently human prostate cancer 3 (PC3) cells were transfected to obtain cells overexpressing Shb in order to increase our understanding of the mechanisms regulating PC3 cell apoptosis.     

Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe₂O₃ NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe₂O₃ NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe₂O₃ NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.     

Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder

This study was designed to compare the effects of fluoxetine and imipramine on fasting blood glucose (FBG) in patients with major depressive disorder. Sixty nondiabetic patients with major depressive disorder (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) entered this randomized, double-blind study. Patients did not receive any medication affecting serum FBG levels for at least 2 weeks before the initiation of the study. Patients were assigned to receive 20 to 40 mg/d of fluoxetine or 75 to 200 mg/d of imipramine for 8 weeks. Pregnant women and patients with diabetes mellitus and a history of any major heart disease were excluded from this study. Additionally, none of the patients should have received electroconvulsive therapy within 6 months before the initiation of the antidepressants. FBG levels were measured at the initiation, as well as 4 and 8 weeks after starting antidepressants. Nineteen patients in the fluoxetine and 24 patients in the imipramine groups completed the study. In the fluoxetine group, FBG level was decreased from 88.5 mg/dL (baseline) to 85.0 mg/dL at week 4 (P = 0.73), and to 79.8 mg/dL at week 8 (P < 0.001). On the other hand, in the imipramine group, FBG level was increased from 86.96 mg/dL (baseline) to 89.71 mg/dL at week 4 (P = 0.079), and to 96.90 mg/dL at week 8 (P < 0.001). This 8-week study showed that FBG levels may decrease in depressive patients receiving fluoxetine and may increase in those patients treated with imipramine. Therefore, it is suggested to measure and monitor FBG before initiation and during treatment with fluoxetine and imipramine.     

Risk factors of thyroid abnormalities in bipolar patients receiving lithium: a case control study

Background

Lithium-induced thyroid abnormalities have been documented in many studies. They may occur despite normal plasma lithium levels. The objectives of this study were: 1) to determine possible relationship between lithium ratio, defined as erythrocyte lithium concentrations divided by plasma lithium concentrations, and thyroid abnormalities in bipolar patients receiving lithium and 2) to find other possible risk factors for developing thyroid abnormalities in the subjects.

Methods

Sixty-eight bipolar patients receiving lithium therapy were enrolled in a cross-sectional evaluation of thyroid function test and thyroid size. Patients were divided into two groups based on their thyroid function tests and thyroid sizes. Erythrocyte and plasma lithium concentrations were determined by atomic absorption spectrometry for each patient. Lithium ratio was then calculated.

Results

No significant differences were found between age, positive family history of affective disorder, plasma lithium concentration, erythrocyte lithium concentration, and lithium ratio comparing the two groups. Thyroid abnormalities was significantly higher in women than in men (p < 0.05).

Conclusions

Lithium ratio does not appear to have a predictive role for thyroidal side effects of lithium therapy. Female gender was the main risk factor. We suggest more frequent thyroid evaluation of bipolar women who are treated with lithium.

     

Effects of cigarette smoking on priapism induced by quetiapine: a case report

Priapism is defined as an unwanted, prolonged, and painful erection which is unrelated to sexual stimulation. Some case studies suggest that priapism is an adverse effect of antipsychotic medications. In our case study a 30 year-old Iranian male with schizophrenia was experiencing recurrent priapism associated with quetiapine use. There are three interesting facts about this case: Firstly, the patient suffered priapism after even low dose consumption of quetiapine. Secondly, this case had experienced priapism with risperidone, olanzapine, and even clozapine in the past, suggesting a possible pharmacodynamic interaction of antipsychotics and inner biological traits in this particular case. Thirdly, priapism induced by low dose quetiapine was resolved after cigarette smoking.     

Cost-effectiveness of continuous positive airway pressure therapy for moderate to severe obstructive sleep apnea/hypopnea

BACKGROUND: Obstructive sleep apnea/hypopnea (OSAH) is a common disorder characterized by recurrent collapse of the upper airway during sleep, and is associated with an increased risk of motor vehicle crashes (MVCs). Common first-line therapy for OSAH is continuous positive airway pressure (CPAP). We assessed the cost-effectiveness of CPAP therapy vs none for the treatment of OSAH. METHODS: We used a 5-year Markov model that considers the costs and quality-of-life improvements of CPAP therapy, accounting for the gains from reduced MVC rates. Utility values were obtained from published studies. The MVC rates under the CPAP and no-CPAP scenarios were calculated from National Highway Traffic Safety Administration data and a systematic review of published studies. Costs of MVCs, equipment, and physicians were obtained from US Medicare and the National Highway Traffic Safety Administration. The target population included male and female patients aged 25 to 54 years and newly diagnosed as having moderate to severe OSAH. We examined the findings from the perspectives of a third-party payer and society. RESULTS: From a third-party payer or a societal perspective, CPAP therapy was more effective but more costly than no CPAP, with incremental cost-effectiveness ratios of $3354 or $314 per quality-adjusted life-year gained, respectively. The incremental cost-effectiveness ratio estimate was most dependent on viewpoint (varying more than 10-fold between societal and third-party payer perspectives) and choice of utility measurement method (varying more than 5-fold between the use of standard gamble and EuroQol 5D utility assessment values). CONCLUSION: When quality of life, costs of therapy, and MVC outcomes are considered, CPAP therapy for patients with OSAH is economically attractive.     

Memantine-induced speech problems in two patients with autistic disorder

Stuttering is a complex speech disorder. There are two forms of stuttering: developmental stuttering and acquired stuttering. Developmental stuttering is a disorder of early childhood but acquired stuttering can develop at any age. Some medications can induce or deteriorate stuttering as an adverse effect. There are several reports of stuttering due to psychotropic drugs. Memantine, a glutamate antagonist used in the treatment of Alzheimer’s disease, has also been studied for the treatment of autism spectrum disorders. This report presents deterioration of stuttering and speech problem in two children with autistic disorder who were receiving memantine. Based on our knowledge, this is the first time these adverse drug reactions have been attributed to memantine. In conclusion clinicians should consider that speech problems including stuttering may be due to the consumption of memantine, especially, in children may be a side effect of memantine especially in children.     

Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake in human prostate cancer cell aggregates

The purpose of this study was to investigate the potential use of PET in vivo to record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on human prostate cancer cell (PC3) aggregates in vitro, were correlated with the uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with 18F, 11C, or 3H. 2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose-dependent manner. However, the uptake of the putative proliferation markers 11C-FMAU or 3H-choline failed to record the growth inhibitory effects of 2-ME on PC3 cell aggregates. The uptake of 18F-FDG was used as a marker for effects on cellular metabolism and also failed to show any dose-dependent effects in PC3 aggregates. The use of these PET-tracers in vivo is therefore not recommended in order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.