Retrial queue MMPP/M/N under heavy load condition

In the paper, a multi-server retrial queueing system with MMPP arrivals is considered. The service and retrial times are exponentially distributed. The two-dimension stochastic process of number of calls in the orbit and states of service unit is analyzed. The system of Kolmogorov differential equations is composed. The matrix form of the equations in steady-state regime for partial characteristic functions is written. The method of asymptotic analysis under the heavy load condition for its solving is proposed. It is proved that the asymptotic characteristic function of the number of calls in the orbit has the gamma distribution with obtained parameters. Some numerical examples of comparison asymptotic and simulate distributions are presented

Resource retrial queue with two orbits and negative customers

In this paper, a multi-server retrial queue with two orbits is considered. There are two arrival processes of positive customers (with two types of customers) and one process of negative customers. Every positive customer requires some amount of resource whose total capacity is limited in the system. The service time does not depend on the customer’s resource requirement and is exponentially distributed with parameters depending on the customer’s type. If there is not enough amount of resource for the arriving customer, the customer goes to one of the two orbits, according to his type. The duration of the customer delay in the orbit is exponentially distributed. A negative customer removes all the customers that are served during his arrival and leaves the system. The objects of the study are the number of customers in each orbit and the number of customers of each type being served in the stationary regime. The method of asymptotic analysis under the long delay of the customers in the orbits is applied for the study. Numerical analysis of the obtained results is performed to show the influence of the system parameters on its performance measure

Asymptotic analysis of MMPP/M/1 retrial queueing system with unreliable server

In this paper, we study a single-server retrial queueing system with arrival Markov Modulated Poisson Process and an exponential law of the service time on an unreliable server. If the server is idle, an arrival customer occupies it for the servicing. When the server is busy, a customer goes into the orbit and waits a random time distributed exponentially. It is assumed that the server is unreliable, so it may fail. The server’s repairing and working times are exponentially distributed. The method of asymptotic analysis is proposed to find the stationary distribution of the number of customers in the orbit. It is shown that the asymptotic probability distribution under the condition of a long delay has the Gaussian form with obtained parameters

N-acetyltransferase 2 (NAT2) Gene Polymorphisms and the Effectiveness of Infertility Treatment in Patients with Peritoneal Endometriosis

Today, infertility has become a global issue. WHO ranks it the fifth among the major diseases of those below 60 years, after alcoholism, depression, injuries and eyesight disorders. Numerous studies conducted on the problems of infertility in endometriosis still do not offer clear answers regarding the pathogenesis and mechanisms of this disease and its influences on fertility. According to the survey results, point mutations of the NAT2 gene (NAT2*5 and NAT2*6) have been identified in 75.6% of the patients with infertility problems and the peritoneal form of endometriosis, that create “slow” allelic variants, which exceed the average index in the population. The peculiarities of the NAT2 gene polymorphisms have been proven to be associated with the effectiveness of the infertility treatment of female patients with peritoneal endometriosis. In the group of non-pregnant patients, the presence of с.341Т>C, c.481C>T, c.590G>A and c.803A>G heterozygous point mutations are 73.2, 73.2, 5.4, and 62.5%, respectively. The significant difference in the comparison of the allelic polymorphism during the various stages of the endometriosis was not identified. At stage III-IV endometriosis the frequency of three and more point substitutions was significantly higher. NAT2 gene polymorphisms can find use as an additional criterion for predicting the effectiveness of the infertility treatment of patients with peritoneal endometriosis

Prednisolone Targets Claudins in Mouse Brain Blood Vessels

Endothelial cells in brain capillaries are crucial for the function of the blood–brain barrier (BBB), and members of the tight junction protein family of claudins are regarded to be primarily responsible for barrier properties. Thus, the analysis of bioactive substances that can affect the BBB’s permeability is of great importance and may be useful for the development of new therapeutic strategies for brain pathologies. In our study, we tested the hypothesis that the application of the glucocorticoid prednisolone affects the murine blood–brain barrier in vivo. Isolated brain tissue of control and prednisolone-injected mice was examined by employing immunoblotting and confocal laser scanning immunofluorescence microscopy, and the physiological and behavioral effects were analyzed. The control tissue samples revealed the expression of barrier-forming tight junction proteins claudin-1, -3, and -5 and of the paracellular cation and water-channel-forming protein claudin-2. Prednisolone administration for 7 days at doses of 70 mg/kg caused physiological and behavioral effects and downregulated claudin-1 and -3 and the channel-forming claudin-2 without altering their localization in cerebral blood vessels. Changes in the expression of these claudins might have effects on the ionic and acid–base balance in brain tissue, suggesting the relevance of our findings for therapeutic options in disorders such as cerebral edema and psychiatric failure

Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review)

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of the adrenal cortex characterized by impairment of cortisol biosynthesis (with possible impairment of aldosterone biosynthesis) and excessive pituitary ACTH release, which promotes oversecretion of intact pathways products: 17-hydroxyprogesterone (17OHP), progesterone, and adrenal androgens – androstendione and testosterone. 21-hydroxylase deficiency, being the most common cause of congenital adrenal hyperplasia is a chronic disorder, that requires life-long glucocorticoid treatment, that aims both to replace cortisol and prevent ACTH-driven androgen excess. Nevertheless, reaching the optimal glucocorticoid dose is challenging because currently available glucocorticoid formulations cannot replicate the physiological circadian rhythm of cortisol secretion. The difficulties in striking the balance between uneffective normalizing of ACTH-level and excess glucocorticoid exposure leads to different abnormalities, that starts to develop at first months of life and progress, frequently gaining especial clinical meaning in adult age. In the present clinical case we introduce 35 years old male patient with salt-wasting form of 21-hydroxylase deficiency, which had either complications considered to progress due to insufficient glucocorticoid therapy, and some metabolic abnormalities, associated with supraphysiological doses of glucocorticoids

Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report)

This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients’ glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice