Changes of B and T lymphocytes and selected apopotosis markers in Hashimoto's thyroiditis

The aim was to assess changes of B and T lymphocytes and selected apoptotic markers in Hashimoto thyroiditis (HT) cases on the basis of quantitative immunohistochemical studies (CD20, CD43, CD8, Bcl-2, caspase-3). The control group comprised colloid goitres without inflammatory infiltrate taken from 10 female patients. Thyroid specimens were obtained retrospectively from 40 patients. The immunohistochemical reactions were subject to quantitative evaluation performed using image-processing methods, including a spatial visualisation of the markers' expression. The percentage of Bcl-2 reactions in HT (mean 3.65%, SD 2.94%) was significantly lower than in the control group (mean 13.99%, SD 5.04%), while the thyroid follicles in HT samples exhibited a higher degree of staining for caspase-3 (mean 1.10%, SD 1.03%) in contrast to normal control tissues (mean 0.48%, SD 1.02%). The results from this study indicate that apoptosis plays a major role in the patogenesis of autoimmune thyroid diseases containing the main pathogenic events in the lesion of thyroid follicular cells in HT. Moreover, the reactivity of CD43 and CD20 was significantly higher in Hashimoto disease, while CD8 was not significantly different from the control group.     

Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the locus coeruleus (LC). DSP-4 treatment of rats on the first and third days after birth produces a long-lasting lesion of noradrenergic neurons in the prefrontal cortex (PFC). In DSP-4-lesioned rats, studied as adults, we observed a decrease in norepinephrine content, with no significant change in the levels of dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA). There is now a well established interaction between noradrenergic and GABAergic systems, whereby the noradrenergic system is involved in the regulation of basal GABA release, while GABAergic neurons simultaneously exert tonic inhibitory regulation of LC norepinephrine neurons. We examined GABAergic neurotransmission in the norepinephrine-denervated PFC for a better appreciation of the interaction between these two systems. Treatment with the GABA transaminase inhibitor vigabatrine (VGB) increased the GABA level of PFC (tissue content) in both intact and lesioned groups. Additionally, VGB increased extracellular GABA concentration in the PFC in both control and DSP-4-lesioned animals, but the elevation of GABA was 2-fold higher in DSP-4 lesioned rats. These findings indicate that neonatal DSP-4 treatment increases GABAergic neurotransmission in the PFC of rats in adulthood, perhaps by decreasing reactivity of central GABA(A) receptors.     

Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers

Objective The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. Methods Two hundred and eighty-five colorectal cancer patients and 275 controls from five hospitals in the European part of Russia were genotyped for the polymorphisms −129T > C (rs3213619) in exon 1b, 2677G > T/A (rs2032582), and 3435C > T (rs1045642) in this population-based case-control study. Genotype-phenotype analysis was performed with simultaneous consideration of lifestyle risk factors. Results Our analysis confirmed the preponderate impact of smoking on colorectal cancer development. The risk of heavy smokers (≥60 pack years) to develop colorectal cancer by far exceeded that of lifelong non-smokers (OR = 3.9, 95% CI: 1.4 to 10.6). Smoking is a more potent risk factor than is the genetic influence of MDR1 in our study. However, a smoking and age-stratified analysis, revealed a statistically significant association between MDR1 genotypes and colorectal cancer in life-long non-smokers with an age ≥63 years (the median age in our sample). The association was stronger for rectal cancer than for colon cancer. Patients who carried the genotypes (−129TT; 2677GG; 3435CC) or (−129TT; 2677TT; 3435TT) developed more frequently colorectal cancer than others (OR = 3.9; 95% CI: 2.0 to 7.7). Conclusions Our results show that the interaction of genetic and lifestyle risk factors should be taken into account to elucidate the genetic influence of MDR1 variability on cancer susceptibility.     

The significance of genetic polymorphisms of factor V leiden and prothrombin in the preeclamptic polish women

Many studies established that gestational hypertension (GH) and preeclampsia (PE) are multifactorial diseases and disturbances in coagulation cascade have etiological significance. Inherited thrombophilias, like polymorphism of factor V (FV) Leiden and prothrombin (PTM) are considered to be involved in the PE development. The aim of this study was to determine the association between FV Leiden and G20210A of PTM gene polymorphism and GH/PE appearance. The study comprised 235 women: GH (n = 126, mean age 27.5 ± 6.0 years), mild PE (n = 41, mean age 28.3 ± 5.7 years), and severe PE (n = 68, mean age 28.5 ± 5.7 years). The control group consisted of 400 healthy pregnant women (mean age 27.5 ± 4.7 years). All women included in the study were white Caucasian of Polish origin, and were singleton pregnancies. The G1691A polymorphism of FV and G20210A polymorphism of PTM were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assays. For PTM G20210A polymorphism overrepresentation of heterozygous GA genotype (7.4 vs. 1.2%, P = 0.02) and of A allele (3.7 vs. 0.6%, P = 0.02) in the group of severe PE have been found. For FV G1691A polymorphism the overrepresentation of genotypes containing at least one mutated allele A (GA and AA) in the group of women with mild (9.7 vs. 3.5%, ns) and severe PE (8.8 vs. 3.5%, ns) was observed. Our results suggest the significant influence of G20210A prothrombin polymorphism and possible influence of G1691A factor V polymorphism in the development of severe preeclampsia.     

The impact of leukemia inhibitory factor in uterine flushing on the reproductive potential of infertile women--a prospective study

PROBLEM: To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome. METHOD OF STUDY: Two phase study. Phase I: assessment of LIF in uterine flushing. Phase II: 1,5 years after examining the last patient, a questionnaire was sent to all participants of the phase I. Phase I: Uterine flushing and endometrial samples were collected during implantation window from infertile patients with stage I/II endometriosis (n = 14), patients with idiopathic infertility (n = 27), luteal phase deficiency (n = 13), and fertile control (n = 21). LIF was assessed in uterine flushings in all patients by ELISA. In endometrium, semiquantitative RT-PCR was performed for LIF mRNA expression. Phase II: questionnaire has been sent to all infertile women taking part in the first phase of the experiment, regarding their reproductive outcome. RESULTS: 65.4% patients who had returned the questionnaire did get pregnant. LIF concentration at a cut-off point of 2.31 pg/ml had a 95.7% sensitivity and 81.8% specificity in predicting the reproductive outcome. CONCLUSION: This prospective study for the first time in literature indicates that the LIF assessment can be used as a predictor of reproductive success.     

Arterial stiffness, central hemodynamics and wave reflection in normal pregnancy and control nonpregnant women

Objectives

Pregnancy is accompanied by different physiological adaptations in the cardiovascular system. However, information on central blood pressures, wave reflection, arterial stiffness in uncomplicated pregnancy compared with nonpregnant women is limited.

Study design

Forty-six women (mean age 28 years) in the third trimester of pregnancy and 45 healthy age- and height-matched controls were evaluated. Arterial stiffness, central hemodynamics and wave reflection was assessed with the use of digital volume pulse analysis and pulse wave analysis.

Results

In comparison with nonpregnant participants, pregnant women had significantly lower mean (p = 0.04) and central systolic (p = 0.02) blood pressure, central pulse pressure (p = 0.02), augmentation index (p = 0.02) and augmentation pressure (p = 0.002), whereas their pulse pressure amplification was significantly higher (p = 0.001). Similarly, arterial stiffness index was higher in pregnant women than in healthy nonpregnant controls (p = 0.006). This index was correlated significantly with central augmentation index and augmentation pressure (r = 0.5, p = 0.0005 and r = 0.52, p = 0.0002, respectively) but only in nonpregnant women.

Conclusions

Healthy pregnancy is associated with increased pulse pressure amplification as well as diminished wave reflection, which results in lower central augmentation index and augmentation pressure. Women in the third trimester of pregnancy have slightly higher arterial stiffness in comparison with healthy nonpregnant, age- and height-matched controls. The increased value of measures of arterial stiffness might be secondary to a known physiological increase of cardiac output and the amount of circulating blood.