Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis

Helicobacter pylori up-regulates cyclo-oxygenase-2 (COX-2) expression, which in turn is involved in tumourigenesis. Recently, a causal link between COX-2 and multidrug resistance 1 (MDR-1) gene expression, implicated in cancer chemoresistance, has been demonstrated. Thus, the expression of COX-2 and the downstream enzyme involved in PGE2 biosynthesis, microsomal PGE-synthase1 (mPGES1), was correlated with P-gp, the product of MDR-1, and the anti-apoptotic protein, Bcl-xL, in gastric biopsies from patients with H pylori infection and in patients with gastric cancer. In a retrospective analysis of endoscopic and pathology files, 40 H pylori-negative patients (Hp-), 50 H pylori-positive patients who responded to eradication therapy (Hp+R), 84 H pylori-positive patients who did not respond to eradication therapy (Hp+NR), and 30 patients with gastric cancer (18 intestinal and 12 diffuse types) were selected. COX-2, mPGES1, P-gp, and Bcl-xL were detected by immunohistochemistry. COX-2, mPGES1, P-gp, and Bcl-xL expression was undetectable in gastric mucosa from Hp- patients. By contrast, COX-2 and mPGES1 expression was detected in 42% and 44% of Hp+R patients, respectively, and in up to 66% (range 63-66%) of Hp+NR patients (p < 0.05). The expression of COX-2 and mPGES1 correlated significantly (p < 0.0001) with that of P-gp and Bcl-xL. High levels of COX-2, mPGES1, P-gp, and Bcl-xL expression were found in intestinal-type gastric cancer samples. In conclusion, H pylori-dependent induction of COX-2 and mPGES1 is associated with enhanced production of P-gp and Bcl-xL that may contribute to gastric tumourigenesis and resistance to therapy.     

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis

OBJECTIVES: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. METHODS: We studied 18 fertile middle-aged normotensive women (48 +/- 1.5 years, range 46-51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. RESULTS: Oophorectomy increased the mean values of 24 h (P < 0.001), daytime (P < 0.05), and nighttime (P < 0.01) diastolic blood pressure and nighttime systolic blood pressure (P < 0.01). Blood pressure increase was associated with a rise in forearm vascular resistance (P < 0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17beta-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. CONCLUSIONS: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.     

p73 G4C14-to-A4T14 gene polymorphism and interaction with p53 exon 4 Arg72Pro on cancer susceptibility: a meta-analysis of the literature

The p73 gene (1p36-33) is involved in cancer development through cell growth inhibition by inducing apoptosis in a p53-like manner. The p73 G4C14-to-A4T14 dinucleotide polymorphism, consisting of two single-nucleotide polymorphisms in the non-coding region of exon 2 that are in complete linkage disequilibrium, has been extensively studied in association with cancer risk. We performed a meta-analysis of published studies that examined the association between this p73 G4C14-to-A4T14 polymorphism and cancer by searching for relevant studies on Medline and Embase up to February 28, 2010. Pooling data from 19 case-control studies that included 6510 cancer cases and 5711 controls, we found that carriers of the p73 G4C14-to-A4T14 homozygous variant genotype (AT/AT) had an increased global risk of cancer [odds ratio (OR) = 1.30, 95% confidence interval (CI), 1.03-1.65]. There was no evidence of an effect modification of p73 AT/AT by age, gender, ethnicity or smoking status in subgroup analyses; however, a 1.35-fold statistically significant increased risk was found among individuals <55 years old. In case-only analysis, the homozygous p73 G4C14-to-A4T14 variant of p73 genotype was associated with the presence of the p53 exon 4 Arg72Pro allele (OR = 1.30, 95% CI, 1.02-1.64), which is suggestive of a biological interaction between the two genes in carcinogenesis. In conclusion, the p73 G4C14-to-A4T14 homozygous variant genotype might be a risk factor for cancer, especially in combination with the p53 exon 4 Arg72Pro polymorphism. Further studies looking at p73 G4C14-to-A4T14 and p53 exon 4 Arg72Pro interaction are required to support our findings.     

Somatoform and psychoform dissociation among women with orgasmic and sexual pain disorders

Since the 20th century, psychogenic female sexual dysfunctions (FSD), like some somatoform and conversion disorders, have been considered an expression of somatoform dissociation. Several studies have reported dissociative symptoms in different somatoform and conversion disorders, but limited data are available on dissociation among patients with FSD. The aim of this study was to assess somatoform and psychoform dissociation among patients with women's orgasmic disorder, dyspareunia, and vaginismus. A battery of self-administered questionnaires (Somatoform Dissociation Questionnaire, Dissociative Experiences Scale, Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised) was given to 200 gynecological outpatients to assess psychoform and somatoform dissociation and their association with FSD. A strong association between somatoform dissociation and FSD was observed (adjusted odds ratio [OR] = 5.39, 95% confidence interval [CI] = 1.15-25.32), the association between somatoform and psychoform dissociation being estimated by an adjusted OR of 4.83 (95% CI = 1.17-19.91). Our results are compatible with the idea that some forms of FSD could be regarded as somatoform dissociative disorders.     

Characterization of Acinetobacter baumannii from intensive care units and home care patients in Palermo, Italy

In this study 45 isolates of Acinetobacter baumannii identified from patients in intensive care units of three different hospitals and from pressure ulcers in home care patients in Palermo, Italy, during a 3-month period in 2010, were characterized. All isolates were resistant to at least three classes of antibiotics, but susceptible to colistin and tygecycline. Forty isolates were non-susceptible to carbapenems. Eighteen and two isolates, respectively, carried the bla(OXA-23-like) and the bla(OXA-58-like) genes. One strain carried the VIM-4 gene. Six major rep-PCR subtype clusters were defined, including isolates from different hospitals or home care patients. The sequence type/pulsed field gel electrophoresis group ST2/A included 33 isolates, and ST78/B the remaining 12. ST2 clone proved to be predominant, but a frequent involvement of the ST78 clone was evident.     

Interleukin (IL)‐17‐producing pathogenic T lymphocytes co‐express CD20 and are depleted by rituximab in primary Sjögren's syndrome: a pilot study

Compelling evidence suggests that interleukin (IL)‐17 and IL‐17‐producing cells play a pivotal role in the pathogenesis of primary Sjögren's syndrome (pSS). We investigated phenotypical and functional effects of the anti‐CD20 antibody rituximab (RTX) on circulating and glandular IL‐17‐producing T cells in pSS. RTX is able to deplete glandular IL‐17⁺ CD3⁺CD4^–CD8^– double‐negative (DN) and CD4⁺ Th17 cells as well as circulating IL‐17⁺ DN T cells. A fraction of glandular and circulating IL‐17⁺ DN cells and CD4⁺ T helper type 17 (Th17) cells co‐expresses CD20 on the cell surface explaining, at least in part, such depletive capacity of RTX. The exposure to RTX does not rescue the in‐vitro corticosteroid resistance of IL‐17⁺ DN T cells. Our results support further the therapeutic role in pSS of RTX that, despite its B cell specificity, appears able to also hamper IL‐17‐producing T cells in this disease.     

H‐ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Macrophage activation syndrome (MAS) is hyperinflammatory life‐threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H‐/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H‐ferritin and L‐ferritin; (ii) CD68⁺/H‐ferritin⁺ and CD68⁺/L‐ferritin⁺; and (iii) interleukin (IL)‐1β, tumour necrosis factor (TNF) and interferon (IFN)‐γ. We also explored possible correlations of these results with clinical data. H‐ferritin, IL‐1β, TNF and IFN‐γ were increased significantly in MAS. Furthermore, an increased number of CD68⁺/H‐ferritin⁺ cells and an infiltrate of cells co‐expressing H‐ferritin and IL‐12, suggesting an infiltrate of M1 macrophages, were observed. H‐ferritin levels and CD68⁺/H‐ferritin⁺ cells were correlated with haematological involvement of the disease, serum ferritin and C‐reactive protein. L‐ferritin and CD68⁺/L‐ferritin⁺ cells did not correlate with these parameters. In conclusion, during MAS, H‐ferritin, CD68⁺/H‐ferritin⁺ cells and proinflammatory cytokines were increased significantly in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H‐ferritin and CD68⁺/H‐ferritin⁺ were associated significantly with haematological involvement of the disease, suggesting biomarkers assessing severity of clinical picture.     

Blue rubber bleb nevus: an uncommon cause of intestinal intussusception

The blue rubber bleb nevus syndrome or Bean syndrome is a rare disorder characterized by cutaneous and gastrointestinal vascular malformations. A 5-year-old girl with Bean syndrome hospitalized in a pediatric unit came under our observation with abdominal pain and vomiting. An X-ray of the abdomen showed an intestinal occlusion and an ultrasonography showed a suspected intestinal invagination. She underwent emergency laparoscopic surgery using three trocars. Laparoscopy revealed a huge ascitis and multiple vascular lesions located on the loops and on the parietal peritoneum, and we identified also an ileo-ileal invagination. We performed a laparoscopic disinvagination that showed one huge vascular lesion producing the invagination and causing a stenosis of intestinal lumen. We performed an intestinal resection after exteriorizing the loops through the umbilicus as well as a termino-terminal ileal anastomosis. Conclusions: Our case shows that an intestinal invagination due to Bean syndrome is extremely rare in pediatric patients but possible. In the emergency, laparoscopy seems to be a safe and effective procedure to confirm the diagnosis and to perform the disinvagination mini-invasivally. In addition, laparoscopy permits to have a clear picture of other intra-abdominal lesions linked to Bean syndrome.     

Role of the neocortex in consolidation of fear conditioning memories in rats

The aim of the present work was to investigate, by means of the reversible inactivation technique, the distinct roles of three neocortical sites, the Prefrontal (PFC), Frontal (FC) and Parietal (PAC) cortices, during memory consolidation of conditioned freezing to a tone, a defined conditioned stimulus (CS), and to the training context. Reversible tetrodotoxin inactivations were performed at increasing post-acquisition delays (0.25, 24 or 96 h). Retention testing was always performed 72 h after the inactivation procedure in order to avoid any possible influence on the retrieval phase. It was found that none of the three sites are involved in context freezing consolidation, but that FC and PAC are differentially involved in the consolidation of memory to the CS. FC inactivation was followed by retention impairment only when performed immediately after acquisition while PAC inactivation was followed by amnesia when performed both immediately after acquisition and 24 h later, but not when performed 96 h later. PFC inactivation was not followed by retention impairment at any of the employed delays. These findings show that some neocortical structures are involved in auditory-cued fear conditioning during the initial phases of the consolidation process.