Outcome of transcatheter aortic valve implantation in high risk patients with severe aortic stenosis

Aim

To assess outcome of TAVI in high risk patients with severe symptomatic aortic stenosis.

Inhibition of the TRPC5 ion channel protects the kidney filter

An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca²⁺ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca²⁺-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease.     

Sertoli cell prostaglandin D2 synthetase is a multifunctional molecule: its expression and regulation

PGD2 synthetase (PGD-S; PGH2 D-isomerase; EC 5.3.99.2) is a bifunctional protein first identified in the mammalian brain. It acts as a PGD2-producing enzyme and a retinoid transporter. PGD-S is present in the testis, where its protein and messenger RNA levels are similar to those in the brain. In view of its diversified regulatory functions, we investigated its regulation using primary cultures of Sertoli cells in vitro to assess its role in the testis. When Sertoli cells were cultured in serum-free medium to allow the formation of specialized junctions, it was found that PGD-S expression increased steadily with time, coinciding with the formation of inter-Sertoli junctions in vitro. However, neither germ cells (using a Sertoli/germ cell ratio between 1:1 and 1:30 when Sertoli cells were cultured at a density of 5x10(4) cells/cm2) nor germ cell-conditioned medium affected the expression of Sertoli cell PGD-S in vitro. These results thus unequivocally demonstrated that germ cells do not play a role in regulating testicular PGD-S expression. Although FSH, dihydrotestosterone, and testosterone had no apparent effect on Sertoli cell PGD-S expression, the addition of progesterone(1x10(-11) to 1x10(-9) M) and T3 (1x10(-11) to 1x10(-9) M) to Sertoli cell cultures elicited a significant increase in PGD-S expression by as much as 4.5- and 2.5 fold, respectively. As PGD-S is a known retinoid transporter, the effects of all-trans-retinoic acid and all-trans-retinal on Sertoli cell PGD-S expression were also assessed. Both compounds were found to induce Sertoli cell PGD-S expression. In summary, PGD-S is a putative Sertoli cell product whose expression is regulated by progesterone, metabolites of vitamin A, and T3. In view of its dual biological properties, a study of its regulation and physiology will yield new insights into understanding its role in the testis.     

Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation

The objective of this study was to develop and optimise self-nanoemulsifying drug delivery system (SNEDDS) of atorvastatin calcium (ATC) for improving dissolution rate and eventually oral bioavailability. Ternary phase diagrams were constructed on basis of solubility and emulsification studies. The composition of ATC–SNEDDS was optimised using the Box–Behnken optimisation design. Optimised ATC–SNEDDS was characterised for various physicochemical properties. Pharmacokinetic, pharmacodynamic and histological findings were performed in rats. Optimised ATC–SNEDDS resulted in droplets size of 5.66?nm, zeta potential of ?19.52?mV, t₉₀ of 5.43?min and completely released ATC within 30?min irrespective of pH of the medium. Area under the curve of optimised ATC–SNEDDS in rats was 2.34-folds higher than ATC suspension. Pharmacodynamic studies revealed significant reduction in serum lipids of rats with fatty liver. Photomicrographs showed improvement in hepatocytes structure. In this study, we confirmed that ATC–SNEDDS would be a promising approach for improving oral bioavailability of ATC.     

Effect of topical anti-inflammatory drugs on corneal and limbal wound healing

PURPOSE: To examine the effect of topical treatment with either steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) on the wound healing of corneal and limbal incisions using histologic criteria. SETTING: Loyola University Medical Center, Maywood, Illinois, USA. METHODS: Eighteen eyes of 9 cats were used for the study. All right eyes received a temporal limbal incision and the left eyes, a clear corneal incision. All eyes were treated with ofloxacin 0.3% postoperatively for 3 days. The animals were equally divided among 3 groups. Group 1 received topical steroid drops (prednisolone acetate 1%) for 7 days maximum; Group 2 received topical NSAID drops (ketorolac tromethamine 0.5%) for 7 days maximum; Group 3 received no additional treatment. One animal from each group was killed and the eye enucleated 3, 7, or 28 days postoperatively. The eyes were processed for staining with hematoxylin-eosin and smooth muscle actin, and corneal sections were evaluated in a blind fashion by an ophthalmic pathologist. RESULTS: Three and 7 days after surgery (1) the limbal incision exhibited more prominent wound healing than the similarly treated clear corneal incision, and (2) the steroid-treated corneas had less wound healing than untreated or NSAID-treated corneas. At 28 days, the wounds in all eyes were almost completely healed. CONCLUSIONS: Limbal incisions heal faster than clear corneal incisions. Steroids, but not NSAIDs, inhibit wound healing. Cataract surgery using limbal incisions and postoperative topical NSAIDs may result in faster wound healing and provide a reduced risk of related postoperative complications.     

Schizophrenia as a temporal mode of being: an existential "ante-festum" impatience.

We suggest in a phenomenological perspective to consider schizophrenia as a special form of human temporality. From this perspective, we view the symptoms of schizophrenia as actions undertaken by subjects to stabilize themselves in existence. From this vantage, we describe the clinical expression of the disorder as a type of "existential impatience", characterized by a painful and elusive "now". This present time posits the prime moment of the constitution of the person. Existential impatience reflects from our patients the persistence of excessive efforts towards individuation. Schizophrenia. In human life in general, individuation consists in an unceasing dynamic process of building up of the self. This process starts with the non-self and particularly with the other. Therefore, the emergence of any relation within the self is grounded in the relation with the other and is based on the relation the other establishes with himself. Schizophrenia distinctly displays the two constitutive moments of "being oneself." These moments are generally linked for all of us: an "unending coming to oneself" (difference of identity), and a "continuous maintenance of being a self" (identity of difference). Existential impatience is not only an irritability of a formal order. Existence itself is impatient in the schizophrenic experience as it hastens to reach human goals while trampling on an "ante-festum" temporal mode. This "before-the-feast" temporal structure is dominated by the shiver before an unknown future, a sign of a basic quest for a task. Schizophrenic "ante-festum" is both a constant fear of being unable to come to oneself and a desperate effort to reach this unknown future. If psychopathology claims to settle [establish] that "order" and "measure" would constitute the two fundamental anthropological bases of human being, impatience of existence draws the emblematic figure of the disorder of measure as a referential motion of the birth of any temporalisation. Such considerations suggest the value, in treatment and rehabilitation, of praising patience and focusing on building, or re-building, the past. The main objective is to reach a maieutics of the self based on relationships in the community and with care-givers, all within an accompanying structured, daily framework.     

Cardiometabolic syndrome: Pathophysiology and treatment

The cardiometabolic syndrome, an interesting constellation of maladaptive cardiovascular, renal, metabolic, prothrombotic, and inflammatory abnormalities, is now recognized as a disease entity by the American Society of Endocrinology, National Cholesterol Education Program, and World Health Organization, among others. These cardiovascular and metabolic derangements individually and interdependently lead to a substantial increase in cardiovascular disease (CVD) morbidity and mortality, making the cardiometabolic syndrome an established and strong risk factor for premature and severe CVD and stroke. Established and evolving treatment strategies including moderate physical activity, weight reduction, rigorous blood pressure control, correction of dyslipidemia, and glycemic control have proven beneficial in reversing these abnormal responses and decreasing the CVD risk.