Effect of early interferon beta-1a therapy on conversion to multiple sclerosis in Iranian patients with a first demyelinating event

BACKGROUND: A new treatment approach to multiple sclerosis (MS) is the initiation of interferon therapy in the early phase of the disease when a patient presents with clinically isolated syndrome. AIMS OF THE STUDY: The goal of this study was to assess the effect of early treatment on the risk of conversion to clinically definite MS in Iranian patients. METHODS: Eligible patients had presented with a first episode of neurological dysfunction suggesting MS within the previous 3 months and had abnormal brain magnetic resonance imaging (MRI). Patients were randomly assigned to receive intramuscular interferon beta 1a 30 mug or placebo once a week for 3 years. RESULTS: Of the 217 patients randomized, 202 patients completed the study; 104 received Avonex and 98 received placebo. Fewer patients converted to clinically definite multiple sclerosis in the treated group than in the placebo group during the study (36.6% vs 58.2%, P < 0.003). The number of active T2-weighted MRI lesions was significantly lower in the treated group. CONCLUSIONS: The results of our study, which are consistent with those from western studies, show that treatment at an early stage of MS delays conversion to definite MS and has positive effects on MRI outcomes.     

The role and regulation of cardiac angiotensin-converting enzyme for noninvasive molecular imaging in heart failure

Congestive heart failure is a pathologic condition characterized by progressive decrease in left ventricular contractility and consequent decline of cardiac output. There is convincing clinical and experimental evidence that the renin-angiotensin system (RAS) and its primary effector peptide, angiotensin II, are linked to the pathophysiology of interstitial fibrosis, cardiac remodeling, and heart failure. In addition to the traditional endocrine or circulating RAS, an active tissue RAS has been characterized. Tissue angiotensin-converting enzyme and locally synthesized angiotensin II, for example, by chymase, exert local trophic effects that modulate gene expression, which regulates growth and proliferation in both myocytes and nonmyocytes. The existence of the tissue RAS offers an opportunity for targeted imaging, which may be of considerable value for guiding medical therapy.     

Successful intracoronary thrombolysis in cocaine-associated acute myocardial infarction

We describe a case of cocaine-associated acute myocardial infarction managed by cardiac catheterization and intracoronary thrombolysis. Based on this and other reported cases, it appears that an invasive approach to the management of cocaine-associated acute myocardial infarction is advantageous over intravenous thrombolysis. Such a strategy would define the pathophysiology of acute myocardial infarction in the setting of cocaine use and allow mechanical intervention should pharmacologic therapy be unsuccessful. Cathet. Cardiovasc. Diagn. 42:294–297, 1997. © 1997 Wiley-Liss, Inc.     

Three-Dimensional Culture Environment Increases the Efficacy of Platelet Rich Plasma Releasate in Prompting Skin Fibroblast Differentiation and Extracellular Matrix Formation

Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.     

Production of intracellular superoxide mediates dithiothreitol-dependent inhibition of apoptotic cell death

Apoptotic cell death proceeds from the activation of cysteine proteinases called caspases. As full enzymatic activity of caspases requires reduction of cysteine residues in and around the catalytic site of the proteases, cysteine- reducing agents such as dithiothreitol (DTT) are expected to facilitate caspase activity upon induction of apoptosis. However, DTT has been shown to efficiently protect cells from apoptosis. The mechanism involved in DTT-mediated inhibition of apoptosis has been attributed to its antioxidant activity. Interestingly, under physiological conditions, thiol-mediated antioxidant reaction has also been shown to result in intracellular generation of superoxide (O(2) (.-)). In line with our earlier findings implicating a slight prooxidant state in resistance to apoptosis, we set out to investigate if the death-inhibitory activity of DTT could be mediated by intracellular O2 (.-). Our results show that incubation of human melanoma cell line M14TF or human bladder carcinoma cell line T24 with DTT induced an increase in intracellular O2 (.-) with concomitant inhibition of apoptosis triggered by CD95 signaling, staurosporine, or hydrogen peroxide. Moreover, preincubation of either cells with Tiron, a specific O2 (.-) scavenger, reverted DTT-induced inhibition of apoptosis. These results show that the apoptosis-inhibitory activity of DTT may not be due to its antioxidant property, but instead linked to its ability to induce an increase in intracellular O2 (.-) level.     

Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review

The liver is a vital metabolic organ for drug and xenobiotic metabolism which is influenced by chemical and natural toxins. Liver injury is associated with systemic oxidative stress, which leads to cellular necrosis, fibrosis, tissue lipid peroxidation, and depletion in glutathione levels. Considering the lack of reliable hepato‐protective drugs in modern medicine, plant‐derived phytoconstituents seem to be a noteworthy option. Naringin is an abundant flavonoid found in citrus fruits with various pharmacological benefits such as antioxidant, anti‐inflammatory, and antiapoptotic, activities. In this review, we summarize available data from recent studies about the hepatoprotective effects of naringin against chemical toxicants and discuss the possible mechanisms of actions.     

Imaging the renin-angiotensin-aldosterone system in the heart

The influence of the renin-angiotensin system (RAS) is recognized in cardiac and vascular injury. An extrinsic RAS has been known for decades, and an equally important intrinsic RAS has been discovered recently. The latter leads to pathologic tissue alterations in the absence of systemic stimuli and may be the main source of local tissue effects of RAS. A new radiotracer [18F]fluorobenzoyl-lisinopril was synthesized by radiolabeling benzoic acid active ester with 18F and reacting that with the epsilon-amino group of lisinopril. The presence of angiotensin-converting enzyme (ACE) activity and angiotensin II receptors was examined in relation to myocardial fibrosis. This tissue-specific radioligand represents the first study of ACE in the human heart. This article presents preliminary data on imaging the RAS in the human cardiac tissue and discusses the potential for clinical application of these imaging techniques to human patients.