Peroxisome proliferator-activated receptor ligands as antiatherogenic agents: panacea or another Pandora's box?

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor super family that modulate gene expression upon ligand activation. They are 3 major subtypes of PPARs: alpha, delta (also called beta), and gamma. PPAR-gamma is widely expressed in the cardiovascular system and is involved in the regulation of tissue inflammation and smooth muscle cell growth pathways as well as in lipoprotein metabolism and coagulation cascades. PPAR-gamma ligands of (e.g., rosigitazone and pioglitazone) have been shown to exert antiatherogenic effects both in vitro and in vivo. PPAR-alpha ligands (e.g., clofibrate and benzofibrate) modulate lipoprotein metabolism, and affect inflammation and coagulation cascade. These effects may be helpful in resolving the dilemma arising from studies that showed significant mortality and morbidity benefits of fibrates in the face of minimal changes in HDL-cholesterol levels. The role of PPAR-delta in atherogenesis remains largely unknown, although it appears that PPAR-delta activation affects lipoprotein metabolism. PPAR ligands appear to be promising agents in limiting atherosclerosis; however, large-scale clinical trials are required to assess their safety and efficacy before they can be added to the clinicians' arsenal of antiatherosclerotic agents.     

Stenting of a superior mesenteric artery lesion via the right arm approach

Chronic mesenteric ischemia is rare and commonly presents with abdominal pain and weight loss. Treatment options are limited to surgical or endovascular revascularization. In this report we describe in detail successful stent-supported angioplasty of a high-grade superior mesenteric artery stenosis utilizing a right brachial artery approach. A brief review of the literature is provided.     

Gram-negative bacillary meningitis

The incidence of gram-negative bacillary meningitis has increased significantly in the past two decades. Approximately two thirds of all reported cases have occurred after neurosurgical procedures. With the development of the newer cephalosporins, the overall mortality rate has decreased from 40 to 80 per cent to 10 to 20 per cent.     

Cephalosporins: rationale for clinical use

Cephalosporins, the most widely used class of antibiotics, are more resistant than penicillins to inactivation by beta-lactamases. Based on their spectrum of activity against gram-negative bacteria, cephalosporins are classified into three generations. The generation classification, however, does not correlate with activity against gram-positive bacteria or anaerobes. First-generation cephalosporins have a narrow gram-negative spectrum but are most active against gram-positive bacteria, particularly Staphylococcus aureus. Third-generation compounds have excellent activity against gram-negative bacteria. The cephamycins, a second-generation subgroup that includes cefoxitin, cefotetan and cefmetazole, have the best activity against anaerobes.     

Efficacy and safety of Iranian made Deferasirox (Osveral®) in Iranian major thalassemic patients with transfusional iron overload: A one year prospective multicentric open-label non-comparative study

Purpose of the study

to determine the efficacy, adverse effects and safety of a new Iranian generic product of deferasirox (Osveral®) in Iranian transfusion dependent major thalassemic (TD-MT) patients.

Methods

In 9 main thalassemia treatment centers, all of TD-MT patients (aged ≥2 yrs) with serum ferritin (SF) levels≥1000 ng/ml, or >100 ml/kg of RBC transfusion,who could not tolerate parental iron chelating were recruited regardless of their previous iron chelation therapy. Periodical clinical and laboratory evaluations were conducted for adverse effects (AEs). Primary efficacy end point was Mean of Relative Change of Serum Ferritin (MRC-SF) from the baseline level during one year. Analysis of variance (ANOVA), t test, chi-square or Fisher exact test were used for statistic analysis appropriately (P values <0.05 were considered as statistical significant).

Results

In 407 cases the male/female ratio was 0.98. Mean age was 11.5±7.4 (2–58) years. The mean of initiating dose of Osveral® and mean usage dose during the study was 23.5±4.9 mg/kg and 24.9±4.9 mg/kg respectively. MRC-SF was −11.44% ±38.92 and it showed significant decline in SF (P value<0.001) one hundred and forty eight patients out of 407 patients experienced at least one. AE, the most common of them were transient increase in serum creatinin (97;24.1%) and>5 time increase in transaminases (24;5.89%).The causes of discontinuation of treatment were non-satisfactory treatment ( 24; 5.8%), poor or non-compliance of patients (21;5.1%), and adverse effects (13; 3.1%)

Conclusion

A detailed comparison with similar studies on deferasirox (Exjade®) shows a promising efficacy and safety for its Iranian generic product (Osveral ®).     

Effects of a small dose of olanzapine on healthy subjects according to their schizotypy: An ERP study using a semantic categorization and an oddball task

Delusions and hallucinations are often meaningful. They thus reveal abnormal semantic activations. To start testing whether antipsychotics act by reducing abnormal semantic activations we focused on the N400 event-related brain potential, which is elicited by meaningful stimuli, such as words, and whose distribution on the scalp is known to depend on the semantic category of these stimuli. We used a semantic-categorization task specially designed to reduce the impact of the variations of context processing across subjects' groups and a classical oddball task as a control. Healthy subjects were recruited rather than psychotic patients to ensure that the medication effects could not be secondary to a reduction of symptoms. These participants (n=47) were tested in a double-blind cross-over paradigm where the ERP effects of 2.5 mg of olanzapine taken on the eve of the testing were compared to those of the placebo. The amplitudes of the N400s elicited by the target words were greater at anterior scalp sites in the half of the subjects having higher schizotypal scores. Olanzapine reduced these larger N400s and had no effect on the small anterior N400s of the half of the subjects with lower scores. These results are discussed as consistent with the idea that antipsychotics reduce abnormal activations of particular semantic representations. Further studies should thus be done to see if this reduction correlates with and predicts the decrease of psychotic symptoms in patients.     

A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications

The rising incidence of obesity and insulin resistance to epidemic proportions has closely paralleled the surge in the prevalence of diabetes and outpaced therapeutic advances in diabetes prevention and treatment. Current evidence points to obesity induced oxidative stress and chronic inflammation as the common denominators in the evolution of insulin resistance and diabetes. Of all the hypoglycemic agents in the pharmacological arsenal against diabetes, thiazolidinediones, in particular pioglitazone, as well as metformin appear to have additional effects in ameliorating oxidative stress and inflammation; rendering them attractive tools for prevention of insulin resistance and diabetes. In addition to their hypoglycemic and lipid modifying properties, pioglitazone and metformin have been shown to exert anti-oxidative and anti-inflammatory effects in vascular beds, potentially slowing the accelerated atherosclerosis in diabetes, which is the major cause of morbidity and mortality in the affected population. The combination of pioglitazone and metformin would thus appear to be an effective pharmacological intervention in prevention and treatment of diabetes. Finally, this review will address the currently available evidence on diabetic cardiomyopathy and the potential role of combination therapy with pioglitazone and metformin.     

Predictors of in-stent restenosis and patient outcome after percutaneous coronary intervention in patients with diabetes mellitus

Diabetics have a significantly higher incidence of major adverse cardiac events (MACEs) and in-stent restenosis (ISR) than nondiabetics after percutaneous coronary intervention (PCI). Predictors of MACEs and ISR are uncertain in diabetics. In recent studies, microalbuminuria and proliferative retinopathy have been believed to relate to progressive coronary atherosclerosis. We retrospectively studied 191 consecutive patients (mean age 65 +/- 9 years) with diabetes who underwent PCI to determine predictors of ISR and MACEs (defined as cumulative incidence of myocardial infarction, revascularization, or death from cardiovascular cause), with special reference to microalbuminuria and proliferative retinopathy. Of 191 patients, 106 (56%) had a follow-up coronary angiogram at 16 +/- 2 months. Of these 106 patients, 66 (62%) developed ISR. In the multivariate model, microalbuminuria or proliferative retinopathy did not achieve significant association with ISR. Serum high-density lipoprotein cholesterol levels were significantly associated with a lower incidence of ISR (odds ratio [OR] 0.928, 95% confidence interval [CI] 0.876 to 0.983, p = 0.011) and MACEs (OR 0.96, 95% CI 0.931 to 1.000, p = 0.048). Use of drug-eluting stents also had a negative association with ISR (OR 0.171, 95% CI 0.05 to 0.585, p = 0.004). Renal insufficiency was associated with higher MACEs (OR 3.19, 95% CI 1.45 to 7.031, p = 0.0039). In conclusion, serum high-density lipoprotein cholesterol levels were inversely associated with ISR or MACEs.