Effect of Wine Polyphenol Resveratrol on the Contractions Elicited Electrically or by Norepinephrine in the Rat Portal Vein

We investigated the effects of resveratrol on rat portal vein (RPV) contractility without endothelium. Contractions were produced by electrical field stimulation of perivascular nerves (EFS), norepinephrine (NE), adenosine 5′‐triphosphate (ATP), high K⁺ solution and by calcium chloride (CaCl₂) in Ca²⁺‐free and high K⁺, Ca²⁺‐free solution. The EFS‐evoked contractions were more sensitive to resveratrol and to NS1619‐selective openers of big calcium‐sensitive (BK_Ca) channels, than NE‐evoked contractions. Effects of resveratrol on the ATP‐evoked contractions were weak. Blockers of BK_Ca channels partly inhibited the effect of resveratrol only in EFS‐contracted preparations. Western blotting showed that RPV expressed K_Ca1.1 protein. Inhibitors of ATP‐ and voltage‐sensitive K⁺ channels did not modify the effects of resveratrol. None of the antagonists of K⁺ channels affected the resveratrol inhibition of NE‐evoked contractions and effect of high concentrations of resveratrol on the EFS‐evoked contractions. Resveratrol more potently inhibited CaCl₂ than potassium chloride contractions of RPV. Thus, BK_Ca channels partly mediate the inhibitory effect of resveratrol on the neurogenic contractions of RPV. The smooth muscle Ca²⁺ channels and/or Ca²⁺ mobilizing through cells might be involved in the effects of resveratrol on the contractility of RPV. Our results are important for better understanding the impact of resveratrol on the portal circulation. Copyright © 2013 John Wiley & Sons, Ltd.     

An evaluation of RVX-208 for the treatment of atherosclerosis

Introduction: RVX-208 is a first-in-class, orally active, novel small molecule in development by Resverlogix Corporation (Calgary, AB, Canada). It acts through an epigenetic mechanism by inhibiting the bromodomain and extraterminal (BET) family of proteins, increasing apolipoprotein A-I (apoA-I) and targeting high-density lipoprotein (HDL) metabolism, including generating of nascent HDL and increased larger HDL particles, resulting in the stimulation of reverse cholesterol transport. RVX-208 also has a beneficial effect on inflammatory factors known to be involved in atherosclerosis and plaque stability. New therapeutic strategies are needed for patients with atherosclerosis.

Areas covered: In this review, the authors evaluate the use of RVX-208 as an agent for the treatment of atherosclerosis. The article is based on a literature search considering both animal and human studies available on PubMed as well as Media Releases from the Resverlogix Corporation.

Expert opinion: The current evidence suggests promising beneficial effects of this novel drug in the prevention and treatment of atherosclerosis and other metabolic disorders. Its unique mechanism of action is encouraging; it affects several pathways and has a modest effect on HDL levels. There is also a shift in particle size to larger HDL particles, which may have potent atheroprotective effects. Future clinical development is needed, including safety assessment.     

Immediate post-traumatic upper incisor reconstruction using composite resin materials.

Single visit reconstruction of the fractured crown can be completed with composite resins if there is no bleeding due to the soft tissue injury. Clinical inspection revealed a complex crown fracture of the central incisor as well as a simple horizontal fracture of the lateral incisor crown of the enamel-dentin type. Vertical fracture separated the palatal enamel wall from the rest of the lateral incisor crown. After the completion of the endodontic sanitation, root canals were prepared for prefabricated composite posts and crown reconstructions were performed with the Finger Tip Technique by using composite resin materials. The advantage of this kind of reconstruction is preservation of the hard dental crown tissue removed in case of prosthetic therapy, especially in younger patients. Reconstruction can be finished in one visit, without the need for a dental technician and laboratory.     

Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment

The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing. The experimental group (15 patients) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning. The control group (15 patients) received topical fluoride treatment (protective varnish for desensitization). All the patients were treated at baseline visit, and then at day 2 and 4 after the initial treatment; the pain was subjectively assessed by the patients as strong, medium, medium low, low, or no pain. Total absence of the dental hypersensitivity was reported in 26.66% of the examined group even after the second visit, compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases. Complete absence of pain was achieved in 86.6% of patients treated with laser and only in 26.6% in the fluoride treated group, after the third visit. Based on our findings, we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing.     

Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates

The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G₁-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.     

Effect of tadalafil on erectile dysfunction in male patients with diabetes mellitus

BACKGROUND/AIM: [corrected] During the first 10 years over 50% of diabetes patients develop erectile dysfunction (ED). It is more severe and resistant to therapy than in male patients with normal glucoregulation. The purpose of this pilot study was to estimate the tadalafil (Cialis) efficacy and safety in male patients with diabetes mellitus (DM), together with moderate to severe ED. METHODS: The study included 30 male patients with diagnozed type 1 or type 2 DM together with ED. ED was estimated through the International Index of Erectile Function (IIEF-6), Sexual Encounter Profile (SEP) questionnaire and prostaglandin test, at the beginning of the research and three months after the 20 mg tadalafil therapy initiation, once a week (on Fridays). Glycosylated haemoglobin in blood (HbAlc) values were also monitored. According to the ED severity (IIEF values at the beginning of the therapy) the patients were divided into 2 groups. The previous experience with sildenafil citrate (Viagra) and prostaglandin E1 intracavernous therapy was recorded. RESULTS: Tadalafil significantly improved ED (p < 0.001) for 7.40 points of the IIEF score, i.e. for 58% and 60% towards SEP2 and SEP3 questionnaire, respectively. Compared to the previous ED therapy subjectively better tadalafil experience was recorded. Each group experienced a significant improvement in IIEF score (p < 0.001), more significantly in the group 2 (8.26+/-1.49 points) compared with the medium improvement in the group 1 (6.27+/-1.35 points). After three months HbA1c values decreased for 2.26+/-1.62 (p < 0.001). CONCLUSION: Tadalafil is an effective tool for treating ED in diabetes patients. In some situations tadalafil application could replace prostaglandin test. The sexual sphere motivation leads to the improvement of glucoregulation in DM patients.