New Drugs for Lowering LDL-Cholesterol.

LDL-Cholesterol (LDL-C) is a well-known risk factor for cardiovascular disease. Although statins are the mainstream treatment for lowering LDL-C level, additional LDL-lowering therapies are needed to reduce residual cardiovascular risk, especially in patients at very high risk, or with hereditary lipid disorderes or statin intolerance. The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator for LDL-Receptor activity and an attractive target for the treatment of hypercholesterolaemia. From its discovery in 2003, several therapeutic approaches to the inhibition of PCSk9 have been proposed. Monclonal antibodies that bind to PCSJ9 received marketing approval in 2015 (alirocumab and evolucumab) or are being evaluated in phase III trials (bococizumab). Many other molecules are in preclinical studies, phase I or II clinical trials. Another point of interest carefully investigated is the cardiovascular benefit of reducing LDL-C using these new molecules. High hopes are invested in them.

Rare Cause of Rhabdomyolysis - Case Report.

Rhabdomyolysis, a syndrome caused by injury to the skeletal muscles, is a condition associated with various signs ranging in from asymptomatic elevation of serum creatine-kinase to acute kidney injury, abnormal heart rate and rhythm, coma and even death. We report the case of a 52-year-old woman who developed rhabdomyolysis following an epileptic seizure. Because a single epileptic seizure does not commonly cause rhabdomyolysis, we tried to identify other contributing factors. The only finding was an electrolyte imbalance due to vomiting. This case had a favorable outcome. Our report highlights the importance of considering rhabdomyolysis in a patient with a recent epileptic seizure, especially when several trigger factors for rhabdomyolysis act simultaneously in the same patient.

Electron microscopy analysis of skin biopsies in CADASIL disease.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited vascular disorder, non-amyloid and non-atherosclerotic, affecting predominantly the central nervous system. We examined samples of skin biopsies from six patients (men, 43-52-year-old), admitted for treatment in the Neurology Clinic regarding the presence of partial motor impairment on upper and lower right limbs, facial asymmetry and phrasing impairment (three of the patients); These three patients had family history remarkable for early-onset strokes: mother and two brothers deceased by early strokes (40-50-year-old). Skin biopsy samples were fixed in glutaraldehyde and post-fixed in osmium tetroxyde. After dehydration, tissue samples were embedded in Epon. Ultrathin sections were mounted on copper grids and stained with uranyl acetate and lead citrate as usual and examined with a transmission electron microscope Phillips CM100. In all cases ultrastructural study showed granular osmiophilic material (GOM) in extracellular locations, between degenerating smooth muscle cells in dermal arteries or in their indentations. Deposits of GOM varied in size and electron density. Degeneration and loss of smooth muscle cells (SMCs) leads to abnormal enlargement of the space between these cells Ultrastructural analysis in three cases showed chromatin condensation and peripheral aggregation of nuclear material suggesting cells entry to apoptosis. These aspects and the marked destruction of the vascular wall were correlated with MRI findings and the severity of clinical manifestations at these patients. Our study showed that findings of GOM deposits, degeneration and loss of SMCs (probably by apoptosis), cell adhesion elements disturbance are characteristic for CADASIL disease and sufficient for diagnose of certainty. Moreover, electron microscopy analysis of skin biopsies is a useful tool for a differential diagnosis and can be considered as first choice method.

[Immunoisolation strategies for the transplantation of pancreatic islets]. / Strategii de imunoizolare pentru transplantul insulelor pancreatice.

Several different types of systems employing selectively permeable membranes and matrix supports for cells have been successfully tested in animals. Results in diabetic animals indicate that these systems can function for periods of several months to several years without the use of any of immunosuppression. This approach has the potential not only to allow the transplantation of islets across wide species barriers but that it can be achieved using injectable microreactors fabricated from biodegradable polymers. A new prototype of minimal volume alginate/polyaminoacidic microcapsules which retain immunoisolatory, biocompatibility and functional properties that seem to match those of conventional-size microcapsules was developed. Since coherent microcapsules tightly envelop each islet, any redundant space between membrane and islet is virtually eliminated. Consequently, these microcapsules occupy an extremely this space, thus addressing a major problem associated with conventional size microspheres.

[The normal functions of integrins and their involvement in pathology]. / Functiile normale ale integrinelor si implicarea lor în patologie.

Ordered cell-cell and cell-matrix adhesive interactions are a fundamental feature of all multicellular organisms. Numerous studies in recent years have confirmed that both types of cell adhesion are mediated by cell surface receptors known as "adhesion molecules". These receptors can be divided into a limited number of families. Knowledge gained from basic research into cell adhesion is now being applied to clinical problems, and some of these have been summarized here. Integrins are heterodimeric proteins mediating cell-cell and cell-extracellular matrix adhesive connections and signal transduction across the plasma membrane. The important roles of integrins are in Leukocyte Adhesion Deficiency, in viral diseases, neural development and cancer. Suggestive data now points to roles in functions characterized in part by morphological rearrangements, such as learning and memory, and injury responses.

The relation zinc-lipidic peroxidation in experimental diabetes mellitus.

The authors investigated the influence of Zn upon glycemy and certain REDOX parametres within the hepatic tissue. The experiment was performed on young Wistar rats with AD, to which Zn sulfate was administered. The values of the antioxidating enzymes: cathalasis and peroxidase decrease in the diabetes' hepatic tissue. The therapy with Zn remakes their activities and increases glutathione synthesis. The Zn protecting effect in lipidic peroxidating process also acts upon hepatocyte membrane, fact illustrated by the decrease of LDH in the plasma of the animals treated with Zn.