The cell cycle regulatory gene polymorphisms TP53 (rs1042522) and MDM2 (rs2279744) in lung cancer: a meta-analysis.

Lung cancer is one of the most common types of cancer in the world. Although the mechanism of lung cancer is still unknown, a large number of studies have found a link between gene polymorphisms and the risk of lung cancer. The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. MDM2 is a critical regulator of the p53 protein. Despite the importance of p53 pathway in cancer, data on the contribution of SNPs of TP53 (rs1042522) and MDM2 (rs2279744) to the development of lung cancer are very contradictory. A metaanalysis that collects quantitative data from individual studies and combines their results has the advantage of improving accuracy, providing reliable estimates, and resolving those issues in which studies on individual associations are not effective enough. The aim of this study was to determine whether the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms confer susceptibility to lung cancer. A meta-analysis was conducted on the associations between the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms and lung cancer. A total of 51 comparison studies including 25,366 patients and 25,239 controls were considered in this meta-analysis. The meta-analysis showed no association between lung cancer and MDM2 (rs2279744) under any model. A noteworthy association of TP53 (rs1042522) with susceptibility to lung cancer in overall pooled subjects was observed under three different models (allele contrast, homozygote contrast (additive) and dominant). Stratification by ethnicity indicated an association between the TP53 (rs1042522) and lung cancer in Asians and Caucasians. This meta-analysis demonstrates that the TP53 (rs1042522), but not MDM2 (rs2279744) polymorphism may confer susceptibility to lung cancer.

Effect of Physical Rehabilitation on Echocardiographic Parameters in Patients with Acute Coronary Syndrome.

Echocardiographic parameters were assessed in patients with non-ST segment elevation acute coronary syndrome, who underwent emergency percutaneous coronary intervention followed by various outpatient physical cardiac rehabilitation programs. The patients underwent physical rehabilitation for 3 months under conditions of diagnostic centre in the rehabilitation unit according to the standard program including in treadmill or bicycle exercise in the exercise therapy room or with Nordic walking in the main training block. After rehabilitation course, the left ventricular mass index significantly decreased and systolic volume and left ventricular ejection fraction significantly increased in both groups. Nordic walking training for 3 months non-ST segment elevation acute coronary syndrome induced similar positive shifts in the parameters of intracardiac hemodynamics, as standard treadmill or bicycle training program, which allows considering it as an alternative cardiac rehabilitation method.

Integrity of mTORC2 is dependent on the rictor Gly-934 site.

Growth factor signaling coupled to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway plays a crucial role in the regulation of cell proliferation and survival. The key regulatory kinase of Akt has been identified as mammalian target of rapamycin complex 2 (mTORC2), which functions as the PI3K-dependent Ser-473 kinase of Akt. This kinase complex is assembled by mTOR and its essential components rictor, Sin1 and mLST8. The recent genetic screening study in Caenorhabditis elegans has linked a specific point mutation of rictor to an elevated storage of fatty acids that resembles the rictor deficiency phenotype. In our study, we show that in mammalian cells the analogous single rictor point mutation (G934E) prevents the binding of rictor to Sin1 and the assembly of mTORC2, but this mutation does not interfere with the binding of the rictor-interacting protein Protor. A substitution of the rictor Gly-934 residue to a charged amino acid prevents formation of the rictor/Sin1 heterodimer. The cells expressing the rictor G934E mutant remain deficient in the mTORC2 signaling, as detected by the reduced phosphorylation of Akt on Ser-473 and a low cell proliferation rate. Thus, although a full length of rictor is required to interact with its binding partner Sin1, a single amino acid of rictor Gly-934 controls its interaction with Sin1 and assembly of mTORC2.

[Atheroscleotic vascular lesion in systemic lupus erythematosus and antiphospholipid syndrome in men].

The aim of the study was to determine the prevalence of various clinical and subclinical manifestations of atherosclerosis (AS) in men with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS), as well as to evaluate correlations between vascular atherosclerotic lesions, risk factors, and the levels of C-reactive protein (CRP) and cardiolipin antibodies (CLA). The subjects of the study were 62 patients (mean age 35.7 +/- 11.6 years, disease duration 129 +/- 102 months). Conventional and disease-related risk factors were analyzed. Carotic ultrasonography (CU) was performed in order to reveal vascular atherosclerotic lesions. Serum CRP levels were measured by the high-sensitive immunonephelometric technique. IgG and IgM CLA were studied by solid-phase immunoenzyme assay. CU found carotic arterial involvement in 58% of the patients; clinical manifestations of AS were revealed in 42% of the patients. The patients were divided into two groups: group I included 19 patients with APLS signs, group II consisted of 43 patients without APLS symptoms. The disease duration and lesion index were higher in group I. The study revealed a significant correlation between CRP level and intima-media complex (IMC) thickness in patients suffering from SLE with or without APLS (p < 0.05). Patients with AS displayed higher levels of IgG CLA, although the difference was insignificant. The study demonstrates that men suffering from SLE with or without APLS have a high risk of AS. An increase in CRP level is associated with an increase in IMC thickness.

[Atherosclerotic lesion of the vessels in systemic lupus erythematosus in males: relations with concentration of C-reactive protein].

AIM: To elicit prevalence of clinical and subclinical manifestations of atherosclerosis in men with systemic lupus erythematosus (SLE), to assess correlation between vascular atherosclerosis, risk factors and concentration of C-reactive protein (CRP). MATERIAL AND METHODS: Analysis of conventional and disease-related factors of risk, ultrasonic scanning of the carotid arteries, high-performance enzyme immunoassay for CRP were made in 37 patients (mean age 36.9 +/- 10.7 years, duration of the disease 130.2 +/- 108.2 months). RESULTS: Clinical symptoms of atherosclerosis were seen in 35% patients. By thickness of the intimamedia complex (IMC), the patients were divided into 2 groups. Group 1 consisted of 21 patients with vascular atherosclerosis (IMC > 0.9 mm), group 2--of 16 patients with IMC < 0.9 mm. Mean age, age of the disease onset, body mass index were greater in group 1. A mean CRP concentration in patients with athrosclerosis was significantly higher than in the group without vascular atherosclerosis (p = 0.004). CONCLUSION: SLE men comprise a group of high atherosclerosis risk. An elevated CRP level is associated with thicker IMC.

[Course and therapy of nonpancreatic complications of chronic pancreatitis]. / Techenie i terapiia vnepankreaticheskikh oslozhnenii khronicheskogo pankreatita.

Out of 647 patients with chronic recurrent pancreatitis followed up for 10-12 years 27 patients (4.2%) developed symptomatic gastroduodenal ulcers, 29 (4.5%) multiple gastroduodenal erosions. Ulcers and erosions emerged in patients with pronounced pancreatic bicarbonate insufficiency. Sucralfate treatment produced the best effect, while almagel plus vicalin were superior to gastrozepin. Relapses of ulcerogenesis were registered in 8 cases, multiple erosions in 11 cases, left pleural exudate in 8 cases in the presence of chronic pancreatitis exacerbation. Pancreatocardiac syndrome with cardialgias, a trend to arterial hypotonia, reduced voltage of ECG waves, occasional extrasystolic arrhythmia occurred in 45 patients (7%). It is shown that metabolic disorders of biogenic amines and lowered blood levels of insulin and C-peptide may underlie pathogenesis of pancreatocardiac syndrome.

[Symptomatic diabetes mellitus in patients with chronic recurrent pancreatitis]. / Simptomaticheskii sakharnyi diabet u bo'lnykh khronicheskim retsidiviruiushchim pankreatitom.

Out of 279 patients with chronic recurrent cholepancreatitis 34 (12.2%) developed secondary diabetes mellitus. The secondary genesis of the diabetes was suggested in view of its origin in the presence of chronic pancreatitis and absence of hereditary predisposition, concomitant diseases promoting diabetes onset. The frequency of pancreatitis exacerbations and the degree of pancreatic exocrine insufficiency correlate with the occurrence of symptomatic diabetes. Diminished blood levels of insulin and C-peptide, inhibited response to pancreozymin registered in the patients may be indicative of symptomatic diabetes onset. Ketoacidosis was recorded in 9 patients, diabetic retinopathy in no patients. Ten patients out of 34 patients with chronic pancreatitis with secondary diabetes, 9 of which had episodes of ketoacidosis, received insulin. The sequence chronic cholecystitis-pancreatitis-diabetes was discussed in detail.

[A prospective multiyear study of the course of chronic recurrent pancreatitis]. / Prospektivnoe mnogoletnee issledovanie techeniia khronicheskogo retsidiviruiushchego pankreatita.

It was established during observation over time (within the period from 10 to 12 years) that the overwhelming majority of patients with chronic cholecystopancreatitis and primary chronic pancreatitis progressed to a different degree to enzyme-secreting pancreatic failure according to the pancreozymine tests. At the same time in 2/5 of all the cases, enzyme-secreting failure turned out substantial by the end of the indicated period. During the years of prospective studies, every tenth patient with chronic pancreatitis developed secondary diabetes mellitus. The degree of pancreatic enzyme secretion and carbohydrate metabolism abnormalities depended on the number of disease exacerbations suffered by the patient. Secondary gastroduodenal ulcers occurred in 27 out of 647 patients observed over time, and all the cases were associated with a considerable reduction of pancreatic bicarbonate secretion (according to the secretin test). Pancreatogenous pleural exudate was recorded in 1.4% of all the cases of chronic pancreatitis. During the observation period, 16 out of the 647 patients died from chronic pancreatitis associated with progressive exocrine pancreatic failure and malabsorption.

[Results of the clinical assessment of the pancreotropic properties of pharmacological preparations based on the pancreozymin test]. / Rezul'taty klinicheskoi otsenki pankreotropnykh svoistv farmakologicheskikh preparatov na osnove fonovoi pankreoziminovoi proby.

Altogether 259 tests with intravenous injection of pancreozymin (0.5 Units/kg) were made with and without administering the drugs. It was discovered that isadrin, dopamine, complamin, calcium gluconate, euphylline and papaverine stimulated the pancreatic secretion of lipase and trypsin. It was also found that atropine, the beta-adrenoreceptor blocker propranolol and corinfar, a calcium antagonist, consistently inhibited the pancreatic secretion of the enzymes. All those drugs did not favour the escape of the pancreatic enzymes to the blood according to the criterion of trypsinemia. Administration of prednisolone in a single dose or in courses enhanced the pancreatic secretion of the enzymes, while the increased trypsinemia was only noticed in solitary cases. All the data obtained during studies of the pancreotropic properties of the drugs administered in single doses or in courses are discussed from the stand-point of the clinical significance of the findings.