Mutational analysis of three tumor suppressor genes in two models of rat hepatocarcinogenesis.

An albumin-simian virus 40 (SV40) large T-antigen (T-Ag) transgenic model and a chemically induced model of multistage hepatocarcinogenesis were created in our laboratory to study the molecular mechanisms involved in the genesis and progression of neoplasia in the rat liver. In the study presented here, these two models of rat hepatocarcinogenesis were used to perform a comparative mutational analysis of three tumor suppressor genes involved in hepatic neoplastic growth. By using polymerase chain reaction-single strand conformation polymorphism analysis and sequencing, exons 5-8 of the p53 tumor suppressor gene and a region between nt 4325 and 4479 of the rat mannose 6-phosphate/insulin-like growth factor 2 receptor (M6p/Igf2r) coding sequence were screened. The latter is homologous to the human M6P/IGF2r coding sequence which is mutated in human hepatocellular carcinoma. A complete single strand conformation polymorphism analysis of the entire coding region of the rat adenomatous polyposis coli (Apc) gene was also performed for the first time in rat tumorigenic samples. Twenty-six chemically induced rat hepatocellular carcinomas, 21 neoplasms from the livers of SV40 T-Ag animals, and five immortalized hepatic cell lines from the transgenic rats were evaluated. None of the hepatic tumors exhibited mutations in the regions analyzed. The albumin-SV40 T-Ag transgenic cell line L-60, derived from normal hepatic tissue, had two mutations in contiguous codons of exon 5 of the p53 gene: a GGT --> GTT missense transversion in codon 183 and a silent mutation in codon 184. The transversion, which may affect the DNA binding domain of the p53 protein, probably originated during cell culture and may have been positively selected because it gave a growth advantage to the mutated cells. The studied region of the M6p/Igf2r gene was not found to be mutated in these two models of rat hepatocarcinogenesis. Although M6p/Igf2r, Apc, and p53 have been shown to be mutated in a variety of human hepatic proliferative diseases, our results indicate that aberrations in these genes may not be necessary for liver carcinogenesis in the rat.     

The influence of osteotomy technique on distraction osteogenesis]

The authors reviewed the clinical results of leg lengthening by distraction osteogenesis, where two different osteotomy techniques were used: classical corticotomy according to Ilizarov or osteoclasis. Evaluation of results of 64 patients were bases on orthopedic examination and detailed X-ray analysis which included criteria assessing osseous regeneration rate. In those cases where osteoclasis was performed bone formation in the distraction gap was faster than in after osteotomy. An accelerated rate of regenerate formation, as well as a more active regenerate remodelling was observed. This allowed to shorten the time of external fixator application and an earlier rehabilitation.     

Range of motion in the joints of the upper extremity at different stages of sympathetic reflex dystrophy (SRD)]

Sympathetic reflex dystrophy of the upper extremity is among the most serious complications of trauma injuries. The aim of this paper was to assess the effectiveness of mobilization treatment, augmented by cryogenic temperatures of post trauma SRD of the upper extremity. The material comprised 113 patients treated at the Orthopedic Outpatient Clinic of the J. Babiński Hospital in Breslau during the years 1987-1995. All patients underwent conservative treatment because of post trauma SRD. The effectiveness of cryo-therapy was based on pre- and post-therapy ROM examination. These results were compared to the ROM of the healthy extremity and the degree of ROM limitation was hence calculated. Limitation of ROM was found in all joints of the upper extremity regardless to the stage of the disease. The greatest limitations were found in the joints directly adjacent to the area were the disease was most pronounced. The applied therapy in these cases was found to increase ROM in all patients, with the greatest increase of ROM during stage I and II of the disease.     

Prothrombogenic factors and reduced antioxidative defense in children and adolescents with pre-metabolic and metabolic syndrome.

BACKGROUND: The aim of this study was to examine prothrombogenic factors and antioxidative defense in obese children and adolescents with pre-metabolic and metabolic syndrome, and to analyze insulin secretion and resistance, early glycoregulation disorders and lipid status. METHODS: Insulin sensitivity was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), while insulin secretion was determined using the homeostasis model assessment beta (HOMA-beta). Prothrombogenic factors analyzed were plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Superoxide dismutase and glutathione peroxidase were measured as markers of antioxidative defense. RESULTS: Patients with metabolic syndrome were characterized with increased body mass index (BMI), waist circumference, and HOMA-IR and HOMA-beta levels, and all had increased blood pressure and triglyceride levels, low high-density lipoprotein cholesterol levels, increased PAI-1 levels and reduced antioxidative defense levels. Patients with pre-metabolic syndrome had higher levels of basal and mean insulinemia during an oral glucose tolerance test, higher levels of HOMA-beta and lower levels of antioxidative defense compared to patients with metabolic syndrome. CONCLUSIONS: Negative correlations between antioxidative defense parameters and BMI, abdominal obesity, insulin secretion, systolic blood pressure and atherogenic lipid factors, as well as correlations between PAI-1 and insulin resistance and basal glycemia in the metabolic syndrome group contribute to accelerated atherosclerosis. Positive correlations between PAI-1 and waist circumference and BMI, and negative correlations between BMI and antioxidative defense in the pre-metabolic syndrome patients show that this early stage preceding the metabolic syndrome is also characterized by atherosclerotic complication risks and evident hyperinsulinism and insulin resistance.     

X-linked angiotensin II type 2 receptor gene polymorphism -1332A/G in male patients with essential hypertension

BACKGROUND: The role of AT2R in regulation of blood pressure (BP) was mainly investigated in animal models. It is proposed to be a negative regulator of BP. X-linked AT2R -1332 A/G polymorphism has been denoted as functional. This polymorphism was associated with certain cardiovascular phenotypes in hypertensive patients, but it was poorly investigated in essential hypertension. The aim of our study was to evaluate possible association of -1332 A/G gene polymorphism with essential hypertension in males from Serbian population. METHODS: The study group included 304 men of Caucasian origin, 190 normotensive (NT) and 114 hypertensive (HT), free of cardiovascular disorders. Genotyping was done by PCR RFLP method. RESULTS: G/- genotype was in association with HT (OR 1.6, CI=1.0-2.6, p=0.04). Stratification by age (<40 years, mean 31.65+/-5.29 and >40 years, mean 51.36+/-8.32) pronounced significance only in older males (OR 2.4, CI=1.2-5.0, p=0.02). After adjustment for confounding factors the OR for hypertension remained unchanged and significant (adjusted OR 2.3, CI=1.0-5.4, p=0.04). Conclusion: Hemizygosity for the G allele was found to be susceptibility factor for hypertension in males. Still, clarifying the role of AT2R in development of human hypertension requires further replication studies in larger and different populations.     

It is Not (Always) the Mismatch That Beats You—On the Relationship Between Interaction of Early and Recent Life Stress and Emotion Regulation,an fMRI Study

Brain Topography - Stress may impact the ability to effectively regulate emotions. To study the impact of stressful experiences in early and recent life on emotion regulation, we examined the...     

Endothelial NOS G894 T and MMP-3 5A/6A gene polymorphisms and hypertension in Serbian population

The incidence of hypertension is increasing and it is more common in man than in women. Up to date, MMP-3 5A/6A polymorphism has been associated with artery stiffening and elevated blood pressure, whereas results considering association of endothelial NOS (eNOS) G894 T polymorphism with hypertension are controversial. The aim of our study was to analyze the possible association of eNOS G894 T and MMP-3 5A/6A gene polymorphisms with hypertension in Serbian population. Study sample consisted of 172 hypertensive and 200 normotensive subjects divided by gender. Both female and male group was truncated according to age. All subjects were genotyped for MMP-3 5A/6A and eNOS G894 T polymorphism. There was a significantly higher (P < 0.05) prevalence of 5A/5A genotype in hypertensive females compared to normotensive ones (19.30 % vs. 10.84%) even more pronounced in group > or =50 years, according to its recessive effect. In young males (<40 years), we found 3.7-fold increased risk for hypertension associated with allele 6A (P < 0.01), and 8.1-fold with genotype 6A/6A (P = 0.01) according to recessive model. We found no association of eNOS G894 T polymorphism with hypertension. These results indicate that there were gender- and age-specific differences in association of MMP-3 5A/6A polymorphism with hypertension in Serbian population.     

Rationalizing blood management in orthopedics and traumatology

In recent years there has been growing interest in blood conservation and avoidance of transfusion in patients undergoing orthopedic surgery. The benefits of blood transfusion must be considered and evaluated in terms of risk factors relating to the adverse effects of transfusion. A number of strategies are available to reduce the need for blood transfusion. These strategies are maximally effective if combined to span the pre-operative, intra-operative and post-operative periods. Surgical, anesthetic and pharmacological techniques can reduce blood loss during operation and the use of allogenic blood. This article presents current opinions, on the base of contemporary literature, regarding risks of transfusion and several simple techniques that will reduce the need for transfusion in orthopedic procedures.