CHEK2 1100delC mutation is frequent among Russian breast cancer patients

This study was aimed to assess the role of CHEK2 1100delC mutation in breast cancer (BC) predisposition in Russia. The 1100delC allele was detected in 14/660 (2.1%) unilateral BC cases and in 8/155 (5.2%) patients with the bilateral form of the disease, but only in 1/448 (0.2%) middle-aged control females and in none of 373 elderly tumor-free women. The obtained data point at potentially high clinical relevance of CHEK2 1100delC testing in females of Russian origin and warrant similar case-control studies in ethnically and geographically related regions, especially in Ukraine, Belarus and Baltic countries.     

Trends of infant mortality in Hong Kong (1956–90) and evaluation of preventable infant deaths

Objective: This study describes the time trends for infant mortality in Hong Kong and aims to develop statistical models that can be used to predict changes of infant mortality in places already having low levels of infant mortality.
Methodology: Data on births and deaths of infants in Hong Kong during the years 1956–90 were analysed annually as well as by aggregating the data into seven consecutive quinquennia. To assess the contribution of preventable infant deaths, causes for infant deaths were classified into two broad categories: (i) congenital anomalies; and (ii) preventable diseases. A simple linear regression model was used to analyse the time trend of the mortality rate of the preventable diseases (PIMR) over the seven quinquennia.
Results: During the period 1956–90, the infant mortality rate fell from 60.9 in 1956–5.9 per 1000 in 1990 and the neonatal mortality rate fell from 24.2-3.8 per 1000. There was no clear time trend observed for infant mortality of congenital anomalies. However, the time trend for PIMR (log scale) was very close to a straight line and simple linear regression modelling showed a R² of 0.9970.
Conclusion: As the infant mortality rate (IMR) falls to below 30 per 1000, the further rate of decrease becomes less predictable from the regression model of the IMR. By removing the portion of deaths attributable to congenital anomalies, the further decrease in infant mortality became more predictable down to very low levels of IMR.     

Urinary incontinence symptoms during and after pregnancy in continent and incontinent primiparas

Objective Examine patterns of urinary incontinence during and after pregnancy, as recalled by incontinent and continent primiparas. Study design Primiparous women reporting no pre-pregnancy incontinence, were recruited 6 to 9 months postpartum. Those reporting current continence and demonstrating a negative stress test were considered “Primiparous Continent” (PC, n=64). Those reporting current incontinence and demonstrating a positive stress test were considered “Primiparous Incontinent” (PI, n=57). Subjects self-administered a questionnaire recalling leakage during and after pregnancy. Results Sixteen percent of PC women leaked during pregnancy. Of these, 70% experienced frequent leakage during pregnancy. Seventy-eight percent of PI women leaked both during and after pregnancy. Several patterns arose surrounding leakage frequency for PI women: 19% only leaked frequently during pregnancy, 4% only leaked frequently after pregnancy, and 51% leaked frequently both during and after pregnancy. Conclusion Nearly five times as many primiparous incontinent women, compared with primiparous continent women, leaked during pregnancy.     

血小板衍生生长因子在肺癌中的意义

目的 探讨血小板衍生生长因子(PDGF)在非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)中的表达及意义。方法 采用免疫组织化学法观察了PDGF—A链、PDGF—B链在NSCLC和SCLC中的表达。结果 PDGF—B链的过表达在NSCLC显著增高，PDGF—A链的过表达在两组间无显著性差异。结论 PDGF—A链和PDGF—B链的生物学特征可能有所不同，相比而言，肿瘤微血管的增生与PDGF—B链的关系可能更密切。     

Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats

Objective

To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma.

Methods

Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations.

Results

Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities.

Conclusions

The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.     

Impairment of both nitric oxide-mediated and EDHF-type relaxation in small mesenteric arteries from rats with streptozotocin-induced diabetes

BACKGROUND AND PURPOSE

To investigate whether diabetes affects either or both nitric oxide (NO)-mediated and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in endothelium-dependent relaxation of mesenteric arteries from streptozotocin-induced diabetic rats.

EXPERIMENTAL APPROACH

Wire myography was employed to examine endothelial function of mesenteric arteries. Superoxide levels were measured by L-012 and lucigenin-enhanced chemiluminescence. Western blotting was used to quantify protein expression levels.

KEY RESULTS

Superoxide levels were significantly increased in diabetic mesenteric arteries compared with normal arteries. Diabetes significantly reduced the sensitivity to the endothelium-dependent relaxant, acetylcholine (ACh) in mesenteric arteries. When the contribution of NO to relaxation was abolished by N-nitro-L-arginine (L-NNA) + a soluble guanylate cyclase inhibitor (ODQ), the sensitivity to ACh was significantly decreased in the diabetic arteries compared with normal arteries, indicating an impaired EDHF-type relaxation despite increased expression of intermediate- and small-conductance calcium-activated potassium channels. Conversely, when the contribution of EDHF was inhibited with TRAM-34 + apamin + iberiotoxin, maximum relaxations to ACh were significantly decreased in diabetic compared with normal arteries, suggesting that the contribution of NO was also impaired by diabetes. Basal levels of NO release, indicated by contraction to L-NNA, were also significantly decreased in diabetic arteries. Western blot analysis demonstrated that diabetic arteries had an increased expression of Nox2, decreased pSer⁴⁷³Akt and a reduced proportion of endothelial NO synthase (eNOS) expressed as a dimer, indicating uncoupling.

CONCLUSION AND IMPLICATIONS

The contribution of both NO and EDHF-type relaxations was impaired in diabetes and was caused by increased oxidative stress, decreased pSer⁴⁷³Akt and/or eNOS uncoupling.     

NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia

The gene for Nijmegen chromosomal breakage syndrome (NBS1) plays a role in a variety of processes protecting chromosomal stability. Recently, it was suggested in a Polish case-control study that the founder hypomorphic mutation in NBS1, 657del5, which occurs in approximately 0.5% of Slavic subjects, may be associated with an increased risk of breast cancer (BC). We attempted to validate these findings in Russian subjects, who are also of Slavic descent. Heterozygous carriers for the 657del5 mutation were detected in 2 of 173 (1.16%) bilateral breast cancer cases, 5 of 700 (0.71%) unilateral breast cancer patients, 2 of 348 (0.57%) healthy middle-aged females and in 0 of 344 elderly tumor-free women. The difference between the "extreme" cohorts, i.e., biBC patients vs. elderly controls, approached the formal limit of statistic significance (p=0.046). LOH at NBS1 was detected in only 3 of 5 available breast tumors from NBS1 657del5-carriers. In 2 of these tumors, the loss involved the mutant NBS1-allele. Overall, our data suggest that the NBS1 657del5 allele may contribute only to a limited fraction of breast cancer cases in Russia.     

High frequency of BRCA1 5382insC mutation in Russian breast cancer patients

BRCA1 5382insC variant was repeatedly detected in Jewish breast cancer (BC) families residing in USA and Israel as well as in non-Jewish familial BC patients from Poland, Latvia, Hungary, Russia and some other European countries. However, the distribution of BRCA1 5382insC mutation in unselected BC cases vs. controls has been systematically investigated mainly in Ashkenazi Jews. Here we applied a case-control study design in order to evaluate the impact of BRCA1 5382insC allele on BC incidence in St Petersburg, Russia. High frequency of the BRCA1 5382insC allele was detected in a group of bilateral breast cancer patients (10.4%; 15/144). Randomly selected unilateral BC cases demonstrated noticeable occurrence of BRCA1 5382insC mutation as well (3.7%; 32/857), with evident excess of the carriers in the early-onset (40 years) category (6.1%; 6/99) and in patients reporting breast and/or ovarian tumours in first-degree relatives (11.3%; 11/97). Strikingly, none of 478 middle-aged controls and 344 elderly tumour-free women carried the 5382insC variant. The presented data confirm a noticeable contribution of BRCA1 5382insC mutation in BC development in Russia, that may justify an extended BRCA1 5382insC testing within this population.