Pitavastatin – a new inhibitor of the HMG-CoA reductase: peculiarities of clinical pharmacology and perspectives of its usage in treatment of cardiovascular diseases.

Cardiovascular mortality makes up 66.3 % of the total mortality in Ukraine. Myocardial infarction, stroke, atherosclerosis of peripheral arteries are the diseases caused by atherosclerosis and are prevalent in the mortality structure. One of the most effective means of successful prevention of cardiovascular disease are drugs that reduce the content of atherogenic lipids in the blood. Statins are the first line drugs for the treatment of patients with dyslipidemia and atherosclerosis in accordance with national and international guidelines. The article presents the features of the pharmacokinetics and pharmacodynamics, results of clinical trials and data on the efficacy and safety of a new inhibitor of the HMG-CoA reductase – pitavastatin (Livazo © (Recordati, Italy). Data from several multicenter randomized studies indicate that pitavastatin significantly reduces the level of cholesterol low-density lipoproteins and triglycerides, significantly increases the level of cholesterol high-density lipoproteins after 12 weeks of observation, and contributes to a significant regression of atherosclerotic plaques. It was shown that pitavastatin has a high level of safety and is well tolerated regardless of patients' age and racial origin. Pitavastatin is a new effective inhibitor of HMG -CoA reductase, which has been successfully used in many countries for the dyslipidemia treatment in patients with cardiovascular disease, diabetes, kidney diseases and other comorbid conditions

Dilute ferrimagnetic semiconductors in Fe-substituted spinel ZnGa2_2O4_4

Solid solutions of nominal composition [ZnGa$_2$O$_4$]$_{1-x}$[Fe$_3$O$_4$]$_x$, of the semiconducting spinel ZnGa$_2$O$_4$ with the ferrimagnetic spinel Fe$_3$O$_4$ have been prepared with $x$ = 0.05, 0.10, and 0.15. All samples show evidence for long-range magnetic ordering with ferromagnetic hysteresis at low temperatures. Magnetization as a function of field for the $x$ = 0.15 sample is S-shaped at temperatures as high as 200 K. M\"ossbauer spectroscopy on the $x$ = 0.15 sample confirms the presence of Fe$^{3+}$, and spontaneous magnetization at 4.2 K. The magnetic behavior is obtained without greatly affecting the semiconducting properties of the host; diffuse reflectance optical spectroscopy indicates that Fe substitution up to $x$ = 0.15 does not affect the position of the band edge absorption. These promising results motivate the possibility of dilute ferrimagnetic semiconductors which do not require carrier mediation of the magnetic moment.Comment: 9 pages and 6 figure

Controlled drug release from electrospun PCL non-woven scaffolds via multi-layering and e-beam treatment

Currently, electrospun synthetic bioresorbable polymer scaffolds are applied in regenerative medicine and tissue engineering as targeted drug delivery devices because of their mechanical and physico-chemical properties. To control the rate of polymer degradation and drug release from polymer scaffolds, surface modification techniques are widely used. In this study, paracetamol-loaded poly (ε-caprolactone) electrospun fibrous scaffolds were treated by the pulsed electron beam irradiation. Pure control PCL scaffold, as well as scaffolds with four paracetamol concentrations (2 wt./wt. %, 8 wt./wt. %, 16 wt./wt. %, and 32 wt./wt.%) were modified. The mechanical and chemical properties and morphology of modified materials were examined. The sustained release of the model drug over a period of one hour for both non-treated and treated samples was demonstrated. It was shown that treatment leads to an increase in drug release rate and does not change surface morphology of scaffolds and fibers diameter distribution

Dynamics of parameters of elastic-elastic properties of arterial wall in patients with morbid obesity after conduction of bariatric treatment.

According to the World Health Organization, 2.8 million people die every year from diseases associated with overweight or obesity. Abdominal-visceral form is a serious predictor of mortality from cardiovascular disease. The aim of the work was to evaluate the dynamics of rigidity of the arterial wall in patients with morbid obesity after the administration of bariatric treatment. The study included 22 patients with morbid obesity, 11 women and 11 men (50%). The average age of patients was 41.9 ± 2.38 years. All patients were under the supervision of a multidisciplinary team of State Establishment "Dnepropetrovsk Medical Academy of Health Ministry of Ukraine", which included surgeons, anesthetists, cardiologists and endocrinologists. Weight loss after bariatric treatment of obesity was accompanied by positive changes in the cardiometabolic profile in patients, which was manifested not only by improving blood pressure control, decreasing doses and the number of medications taken, but also reducing the rigidity of the arterial wall, which in turn led to the reduction of the risk of serious cardiovascular events in future

Magnetic phase diagram of cubic perovskites SrMn_1-xFe_xO_3

We combine the results of magnetic and transport measurements with Mossbauer spectroscopy and room-temperature diffraction data to construct the magnetic phase diagram of the new family of cubic perovskite manganites SrMn_1-xFe_xO_3. We have found antiferromagnetic ordering for lightly and heavily Fe-substituted material, while intermediate substitution leads to spin-glass behavior. Near the SrMn_0.5Fe_0.5O_3 composition these two types of ordering are found to coexist and affect one another. The spin glass behavior may be caused by competing ferro- and antiferromagnetic interactions among Mn^4+ and observed Fe^3+ and Fe^5+ ions.Comment: 8 pages, 10 figures, revtex, accepted to Phys. Rev.

A Pearson-Dirichlet random walk

A constrained diffusive random walk of n steps and a random flight in Rd, which can be expressed in the same terms, were investigated independently in recent papers. The n steps of the walk are identically and independently distributed random vectors of exponential length and uniform orientation. Conditioned on the sum of their lengths being equal to a given value l, closed-form expressions for the distribution of the endpoint of the walk were obtained altogether for any n for d=1, 2, 4 . Uniform distributions of the endpoint inside a ball of radius l were evidenced for a walk of three steps in 2D and of two steps in 4D. The previous walk is generalized by considering step lengths which are distributed over the unit (n-1) simplex according to a Dirichlet distribution whose parameters are all equal to q, a given positive value. The walk and the flight above correspond to q=1. For any d >= 3, there exist, for integer and half-integer values of q, two families of Pearson-Dirichlet walks which share a common property. For any n, the d components of the endpoint are jointly distributed as are the d components of a vector uniformly distributed over the surface of a hypersphere of radius l in a space Rk whose dimension k is an affine function of n for a given d. Five additional walks, with a uniform distribution of the endpoint in the inside of a ball, are found from known finite integrals of products of powers and Bessel functions of the first kind. They include four different walks in R3 and two walks in R4. Pearson-Liouville random walks, obtained by distributing the total lengths of the previous Pearson-Dirichlet walks, are finally discussed.Comment: 33 pages 1 figure, the paper includes the content of a recently submitted work together with additional results and an extended section on Pearson-Liouville random walk

Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo

Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?

The hydrolysis of sphingomyelin generates key molecules regulating cell growth and inducing apoptosis. Data from animal cancer models support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. In the intestinal tract, a sphingomyelinase with an optimum alkaline pH has been identified. We recently found that the activity of alkaline sphingomyelinase is significantly decreased in colorectal adenocarcinomas, indicating a potential anticarcinogenic role of this enzyme. To further examine whether the reduction of sphingomyelinase is present already in the premalignant state of neoplastic transformation, we measured sphingomyelinase activities in patients with familial adenomatous polyposis (FAP) and in sporadic colorectal tubulovillous adenomas. Tissue samples were taken from adenomas and surrounding macroscopically normal mucosa from 11 FAP patients operated with ileorectal anastomosis, from three FAP patients with intact colon, from 13 patients with sporadic colorectal adenomas and from 12 controls. Activities of acid, neutral and alkaline sphingomyelinase were measured together with alkaline phosphatase. In FAP adenoma tissue, alkaline sphingomyelinase activity was reduced by 90% compared to controls (P < 0.0001), acid sphingomyelinase by 66% (P < 0.01) and neutral sphingomyelinase by 54% (P < 0.05). Similar reductions were found in the surrounding mucosa. In sporadic adenoma tissue, only alkaline sphingomyelinase was reduced significantly, by 57% (P < 0.05). Alkaline phosphatase was not changed in FAP adenomas, but decreased in the sporadic adenomas. We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation. © 1999 Cancer Research Campaig