Polycythemia vera: gender-related phenotypic differences

In polycythemia vera, gender has recently been shown to influence the JAK2(V617F) allele burden, but its effect on the disease phenotype is unknown. This issue was investigated using the database of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study. The ECLAP Study recruited 1,638 polycythemic subjects and followed for 2.7?±?1.3?years. At study entry, men, compared to women, had a higher prevalence of myocardial infarction (11.3 vs. 5.8%; P??0.05). These data show several gender-related differences both in the thrombotic diathesis and in the prevalence of vascular risk factors of PV patients.     

Consenso intersocietario sulla profilassi antitrombotica in chirurgia protesica dell’anca e del ginocchio e nelle fratture del collo femorale: aggiornamento 2013

Anticoagulant prophylaxis for preventing VTE is a world wide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures. Different guidelines are available in literature with quite different recommendations. None of them is a multidisciplinary effort as the one presented. In 2010 the Italian Society on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the Association of Orthopaedics and Traumatologists of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI), have set down practical suggestions for VTE prophylaxis in hip and knee surgery as well as in femoral neck fracture treatment. This Intersociety Consensus Statement aimed at simplifying the grading system reported in the literature, and its goal was to favour its clinical application. Special focuses addressed fragile patients and those patients at high risk of bleeding or receiving chronic antiplatelet and vitamin K antagonists treatment, and a special chapter was dedicated to regional anaesthesia and VTE prophylaxis. The registration of three novel oral anticoagulants (dabigatran, rivaroxaban and apixaban) for VTE prophylaxis in major orthopedic surgery and the ongoing introduction of these drugs for the prevention of embolism in atrial fibrillation make it necessary an update of the Intersociety Consensus Statement.     

Sensorimotor evaluation of ano-rectal complex in diabetes mellitus.

To evaluate the status of ano-rectal complex in diabetic patients, 20 patients with no fecal incontinence and/or local ano-rectal disorders and 18 normal subjects underwent to: 1) ano-rectal manometry; 2) defecography; and 3) rectal sensation tests. In all subjects, the five classic cardiovascular reflexes tests were performed to detect autonomic neuropathy. No significant difference between diabetic patients and controls was found in length, maximum resting pressure and strength of phasic external anal sphincter or anal canal at ano-rectal manometry; similarly, no significant difference between diabetic and normal subjects was found by the same technique in threshold and amplitude of ano-rectal inhibitory reflex. Ano-rectal angle of diabetic patients was not significantly different from normals both at resting and during straining at defecographic study. By rectal sensation testing, it was possible to demonstrate a significant difference between diabetic and normal subjects in perception of rectal distension (87.5 +/- 27.5 vs 39.2 +/- 6.5 ml, p less than 0.05; mean +/- SEM) and of stimulus of defecation (147.0 +/- 56.3 vs 52.9 +/- 18.5 ml, p less than 0.001) but not in perception of maximum tolerable volume (343.5 +/- 69.9 vs 322.0 +/- 48.5 ml, p = NS). No relationship was found between these results and the score of autonomic neuropathy and/or duration of diabetic disease. These data suggest that an early involvement of only sensory parasympathetic fibers of ano-rectal complex occurs in diabetic patients without gastrointestinal symptoms.     

Benzydamine inhibits the release of tumor necrosis factor-α and monocyte chemotactic protein-1 byCandida albicans-stimulated human peripheral blood cells

Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on arachidonic acid metabolism, which is extensively used as a topical drug in inflammatory conditions, particularly for the treatment of bacterial vaginosis andCandida albicans-sustained vaginitis. In the present study the effects of benzydamine on the production of several inflammatory cytokines were examined in cultures ofCandida albicans-stimulated human mononuclear cells. Benzydamine (6.25-50 ΜM) inhibitedCandida-induced tumor necrosis factor-α and, to a lesser extent, interleukin-1 Β production, whereas it did not affect interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1 secretion, but it did not affect interleukin-8 production. Unlike benzydamine, ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used topically, were unable to suppress inflammatory lymphokine production fromCandida-activated mononuclear cells. These data suggesrthat benzydamine may be effective in localCandida infections at least in part by suppressing inflammatory cytokine and monokine production in the vaginal mucosa and consequently decreasing their levels in vaginal secretions.     

NSAID enteropathy: could probiotics prevent it?

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world; nevertheless, about 50–70 % of patients on long-term NSAIDs develop small intestine injury, namely NSAID enteropathy, sometimes with serious outcomes. No medications with proven efficacy are yet available to prevent NSAID enteropathy. A series of therapeutic strategies targeting the different mechanisms involved in small bowel injury have been investigated, but without definitive results. Intestinal bacteria and their degradation products are essential for the development of NSAID-induced small bowel lesions, because “germ-free” animals were found to be resistant to indomethacin injuries. Therefore, it has been suggested that modulating the intestinal flora, for example by using probiotics, could protect against NSAID enteropathy. In this work, we reviewed the main therapeutic strategies for NSAID enteropathy, in particular analyzing the available studies relating to the eventual protective role of probiotics. We found that results are not all concordant; nevertheless, the more recent studies provide better understanding about pathogenetic mechanisms involved in small intestinal injury and the role of probiotics, and show encouraging results. Larger and well-designed studies should be performed to evaluate the actual role of probiotics in NSAID enteropathy, the eventual differences among probiotic strains, dose-responses, and optimal duration of therapy.     

Mismatch repair,p53 and beta-catenin proteins in colorectal cancer

BACKGROUND: Mismatch repair (MMR) proteins (MSH2 and MLH1) deficiency is responsible for microsatellite instability (MSI) status. We evaluated p53 and beta-catenin expressions in colorectal cancer specimens with known microsatellite status, previously assessed by means of the polymerase chain reaction (PCR). We also analyzed the MMR proteins immunostaining and compared the results with those ascertained by PCR. MATERIALS AND METHODS: Twenty-five colorectal cancer patients were analyzed for immunohistochemical expression of p53, beta-catenin, MSH2 and MLH1 proteins. RESULTS: The microsatellite status was only significantly correlated with p53 expression and MRR proteins pattern. CONCLUSION: We demonstrated a significantly higher p53 expression in MSI colorectal specimens. The concordance rate between immunohistochemistry and PCR was so high (80%) that the immunohistochemical technique can be proposed as a method to select MSI patients for improved outcome and response to chemotherapy.     

Interleukin-1-beta modulation of prolactin secretion from rat anterior pituitary cells: involvement of adenylate cyclase activity and calcium mobilization

Recent findings indicate that interleukin-1 beta (IL1 beta), a monokine secreted by stimulated macrophages and monocytes, modulates neuroendocrine functions in a manner similar to classical hormones. In this study we show that IL1 modulates PRL secretion, assessed by reverse hemolytic plaque assay, and describe the effect of the monokine on adenylate cyclase activity and calcium fluxes in rat normal pituitary cells. In basal and vasoactive intestinal peptide (VIP)-stimulated conditions, low doses of IL1 reduced the mean plaque area, a direct index of PRL secretion without affecting the percentage of PRL-secreting cells. Similarly, low concentrations of IL1 inhibited adenylate cyclase activity in both basal and VIP-stimulated conditions, while higher concentrations restored the enzymatic activity to the control value. IL1 also caused a biphasic effect on the free intracellular calcium increase induced by maitotoxin, a calcium channel activator, being inhibitory at low and stimulatory at high concentrations. The effects of IL1 on adenylate cyclase activity and calcium fluxes were reversed by preincubation of the monokine with its polyclonal antibody, thus confirming the specificity of the effects. In conclusion, our data show that IL1 modulates PRL secretion by acting directly on pituitary cells through interaction with the adenylate cyclase-cAMP system and calcium flux.