Altered dopamine signalling in chronic epigastric pain syndrome.

Chronic epigastric pain syndrome (CEPS) is an important diagnostic problem, especially in patients without macroscopic and microscopic changes in gastric mucosa. The cause of this ailment is unclear. The aim of this study was the assessment of coexistence between symptoms of this syndrome and secretion level of dopamine (DA), as well as the efficacy of peripheral and central D2 receptors antagonist. Sixty depressive patients with CEPS occurring independently of the diet and with no Helicobacter pylori infection and 30 healthy subjects were enrolled in this study. Plasma DA and urinary homovanilic acid (HVA) concentration were measured by ELISA, and the mRNA expression of dopa decarboxylase (DDC) in gastric mucosa was evaluated by RT-PCR in 30 patients with CEPS and 30 controls. Severity of epigastric pain before and after 12 weeks 2 x 50 mg itopride or sulpiride treatment was evaluated using the modified 10-point Visual Analogue Scale. Higher average levels of plasma DA and urinary HVA levels in CEPS patients than controls 129.5 ± 22.0 versus 109.1 ± 18.4 pg/ml (p < 0.001) and 6.82 ± 1.55 versus 5.39 ± 1.04 mg/24 h, respectively were obtained. Moreover, the expression of DDC in gastric mucosa of CEPS patients was higher than in healthy subjects (p < 0.01). Sulpiride subsided epigastric pain in 73.3%, but itopride reduced it only in 6.6% of CEPS patients. We concluded that altered dopamine signalling may affect locally-and-centrally mediated chronic epigastric pain.

Polymorphism of DNA mismatch repair genes in endometrial cancer.

UNLABELLED: Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. AIM: We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a -93G>A (rs1800734) transition in the promoter of the hMLH1 gene. MATERIAL AND METHODS: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. RESULTS: A positive association (OR 4.18; 95% CI 2.23-7.84) was found for the G/A genotype of the -93G>A polymorphism of the hMLH1 gene and EC occurrence. On the ot-her hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the -93G>A-G/A genotype (OR 4.52; CI 2.41-8.49). Our results suggest that the -93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC.

Transfusion of intra-operative autologous whole blood: influence on complement activation and interleukin formation.

BACKGROUND AND OBJECTIVES: Transfusion of autologous whole blood is one available method to reduce the need for allogenic blood transfusion. The objective of this study was to investigate the safety of transfusion of intra-operative autologous whole blood by monitoring plasma concentration of laboratory variables and adverse events after transfusion with the Sangvia(®) system. MATERIALS AND METHODS: The clinical trial was designed as an open, prospective, multi-centre study, and a total of 20 patients undergoing primary hip arthroplasty were included. Systemic blood samples were taken and analysed preoperatively, at transfusion start and end and at 3, 6, 24 and 48 h after the transfusion. RESULTS: Elevated values of complement activation and pro-inflammatory cytokines were seen in the intra-operatively collected blood but the impact on systemic levels were limited with low peak levels, systemic elevations before transfusion and normalization during the study period. Elevated levels of free haemoglobin and potassium were also detected in the intra-operatively collected blood, but systemic values were within reference values after the transfusion. No clinically relevant adverse event occurred during the study. CONCLUSION: Inflammatory mediators and plasma haemoglobin were increased in intra-operatively salvaged and filtered blood compared to circulatory levels. Intra-operative retransfusion of autologous whole blood caused a transient systemic increase that normalized in the early postoperative period. There were no significant adverse events reported in the study. These data suggest that the Sangvia(®) system can be used for intra-operative collection and retransfusion of salvaged blood.

Mutations in the PAX9 gene in sporadic oligodontia.

OBJECTIVES: Oligodontia, a congenital lack of six or more teeth, is often associated with mutations in the PAX9 gene; therefore, we searched for mutations in this gene. DESIGN: In the present work, we sequenced fragments of the PAX9 gene in individuals with sporadic oligodontia. Next, we genotyped some mutations we found in patients with oligodontia and individuals without tooth agenesis. SETTING AND SAMPLE POPULATION: DNA sequencing was performed in the material isolated from peripheral blood lymphocytes of six unrelated patients with sporadic, non-syndromic oligodontia. These patients were selected based upon explorative cluster analysis. Genotyping was performed in 38 patients with oligodontia and 100 control individuals. MATERIAL AND METHODS: Direct sequencing and restriction fragment length polymorphism PCR were employed. RESULTS: We detected two homozygotic substitutions, IVS2-109G>C and IVS2-54A>G, in intron 2 in three patients. Another homozygotic substitution in intron 2, IVS2-41A>G, was revealed in two patients. Two patients had an IVS3+40G>A homozygotic change in intron 3 and 4 patients displayed a 717C>T transition in exon 4 (silent mutation). One patient had a heterozygotic 718G>C transversion, resulting in a missense Ala240Pro substitution. We detected also several other intronic substitutions. Further genotyping of the IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations suggested that they can display polymorphic changes. CONCLUSION: The IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations of the PAX9 gene may represent polymorphism associated with sporadic oligodontia.

[The effect of melatonin on oxidative DNA damage in gastric mucosa cells of patients with functional dyspepsia]. / Wplyw melatoniny na oksydacyjne uszkodzenia DNA w komórkach blony sluzowej zoladka u osób z dyspepsja czynnosciowa.

UNLABELLED: The oxidative damage of DNA expresses severe cell lesion. The excess of oxygen free radicals is one of the causes of this type of disorders. Such a situation could occur in the course of H. pylori infection. Melatonin is a natural and very active antioxidant compound. AIM OF STUDY: To establish weather an administration of melatonin decreases oxidative DNA damage in gastric mucosa cells. MATERIAL AND METHODS: The study comprised 80 subjects, divided into two groups: group I (n=30)--patients with functional dyspepsia, H. pylori positive (+), with Epigastric Pain Syndrome, with H. pylori infection; group II (n=30)--patients H. pylori negative (-) with the same form of functional dyspepsia. The control group (0) comprised 20 subjects, aged 21-60 years. RESULTS: In healthy subjects, non-infected with H. pylori the level of oxidative DNA damage in gastric mucosa cells was 6.95 +/- 2.98. In both study groups the percentage of oxidative DNA damage was respectively: 12.12 +/- 5.48% and 13.62 +/- 4.58% (p < 0.001). The differences in the results obtained in both study groups, that is H. pylori (+) and H. pylori (-) were similar (p > 0.05). In group of patients with functional dyspepsia and H. pylori infection the level of oxidative DNA damage in gastrocytes was 12.12 +/- 5.48%, and after 3 months administration of melatonin it decreased to the value 10.55 +/- 0.63% (p < 0.001). In patients with functional dyspepsia, without H. pylori infection the decrease of the level of oxidative DNA damages after melatonin administration was statistically significant and it was respectively: 13.62 +/- 4.58% (p < 0.001). CONCLUSIONS: In functional dyspepsia, especially with coexisting H. pylori infection the oxidative DNA damage in gastric mucosa cells is observed. The melatonin administration changes the above mentioned oxidative DNA damage significantly.

Promoter methylation of cancer-related genes in gastric carcinoma.

UNLABELLED: Genetic changes associated with gastric cancer are not completely known, but epigenetic mechanisms involved in this disease seem to play an important role in its pathophysiology. One of these mechanisms, an aberrant methylation in the promoter regions of genes involved in cancer induction and promotion, may be of particular importance in gastric cancer. AIM: To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas in gastric cancer patients. METHODS: The methylation pattern of the genes was assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken during surgery of 27 patients and compared with the methylation pattern in material obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions. RESULTS: We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric cancer patients as compared with the controls. Additionally, we investigated the relationship between promoter hypermethylation and age, gender, smoking and gastric cancer family history. The hypermethylation of the hMLH1 gene occurred more frequently in female than in men, and the hypermethylation of the CDH1 gene was observed preferentially in smoking than in non-smoking individuals. CONCLUSION: The data obtained indicate that changes in DNA methylation may contribute to gastric carcinogenesis.

Correlation between aortic pulse wave velocity and norepinephrine, epinephrine, aldosterone and plasma renin activity in very elderly subjects and in patients with congestive heart failure.

The expression of cardiovascular disease in older patients results from the interaction between age-related changes and the disease process itself. It is still unclear whether the physiologic and pathophysiologic changes that occur with advanced age accelerate or compound the factors responsible for congestive heart failure (CHF). Whether, and to what extent, arterial compliance is altered in CHF in the elderly is not clear. It is also unknown whether the plasma levels of neurohumoral factors in the healthy elderly and in CHF patients are associated with changes in arterial compliance. The aim of this study was to evaluate the aortic pulse wave velocity (PWV) in the aorta of elderly healthy subjects and CHF patients, and establish the correlation between PWV and plasma levels of norepinephrine, epinephrine, aldosterone, and renin activity. The study group consisted of 63 females aged 70-100 years (mean, 82 years) with CHF, and 15 age-matched healthy women. Aortic PWV in patients with heart failure did not differ significantly from figures in the age-matched healthy group (12.42 m/sec vs 11.86 m/sec). No statistically significant correlations were found between plasma levels of norepinephrine, epinephrine, aldosterone and renin activity, and aortic compliance measured as PWV. These results suggest that age-associated arterial stiffening is a predominant factor in the development of reduced arterial compliance in elderly patients with CHF.