Manometric evaluation of internal anal sphincter after fissurectomy and anoplasty for chronic anal fissure: a prospective study

Chronic anal fissure (CAF) is a common painful clinical disease and its pathogenesis remains poorly understood. After failure of pharmacological therapy, that is the first-line treatment, sur- gical sphincterotomy remains the treatment of choice although it is followed by a high rate of anal incontinence resulting from the sphincter damage; therefore, the research of a sphincter-saving surgical option has become an important goal. The aim of this study was to evaluate the mano- metric modifications and the incidence of anal incontinence after fissurectomy and anoplasty with advancement skin flap in patients affected by CAF with hypertonia of the internal anal sphincter (IAS). Fifteen patients affected by CAF with hypertonia of IAS, unresponsive to medical therapy, were enrolled. All subjects underwent fissurectomy and anoplasty with advancement skin flap. Anorectal manometry was performed preoperatively and after 6 and 12 months from surgery. Maximum resting pressure (MRP), maximum squeeze pressure (MSP), ultraslow wave activity (USWA), fissure healing, anal continence, and postoperative complications were recorded. All patients healed within 30 days from surgery. No intra- or postoperative complications were recorded except for a case of partial donor site break. No significant modifications of MSP were detected. Six months after surgery, MRP was higher with respect to healthy subjects but signif- icantly reduced in comparison to baseline levels. At 12 months, it was higher have versus 6-month values but significantly lower versus preoperative values. USWA was significantly represented in patients with CAF versus healthy subject. Both at 6 and 12 months, they decreased significantly with respect to preoperative values without significant differences versus healthy subjects. Both at 6 and 12 months, anal continence did not differ with respect to preoperative time. The fissurectomy with anoplasty resulted in a high healing rate without surgical sequelae or anal incontinence. Also, it was able to reduce IAS pressure in the same manner as surgical sphincterotomy or forceful dilatation

Phosphodiester Silybin Dimers Powerful Radical Scavengers: A Antiproliferative Activity on Different Cancer Cell Lines

Silibinin is the main biologically active component of silymarin extract and consists of a mixture 1:1 of two diastereoisomeric flavonolignans, namely silybin A (1a) and silybin B (1b), which we call here silybins. Despite the high interest in the activity of this flavonolignan, there are still few studies that give due attention to the role of its stereochemistry and, there is still today a strong need to investigate in this area. In this regard, here we report a study concerning the radical scavenger ability and the antiproliferative activity on different cell lines, both of silybins and phosphodiester-linked silybin dimers. An efficient synthetic strategy to obtain silybin dimers in an optical pure form (6aa, 6ab and 6bb) starting from a suitable building block of silybin A and silybin B, obtained by us from natural extract silibinin, was proposed. New dimers show strong antioxidant properties, determined through hydroxyl radical (HO°) scavenging ability, comparable to the value reported for known potent antioxidants such as quercetin. A preliminary screening was performed by treating cells with 10 and 50 µM concentrations for 48 h to identify the most sensitive cell lines. The results show that silibinin compounds were active on Jurkat, A375, WM266, and HeLa, but at the tested concentrations, they did not interfere with the growth of PANC, MCF-7, HDF or U87. In particular, both monomers (1a and 1b) and dimers (6aa, 6ab and 6bb) present selective anti-proliferative activity towards leukemia cells in the mid-micromolar range and are poorly active on normal cells. They exhibit different mechanisms of action in fact all the cells treated with the 1a and 1b go completely into apoptosis, whereas only part of the cells treated with 6aa and 6ab were found to be in apoptosis

Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo

Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa−/−). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo

Bone damage after chemotherapy for lymphoma: a real-world experience

Abstract Background: Despite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures. Aim: To provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy. Method: A cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques and screening tools for the assessment of functional status and quality of life (SARC-F and mini-Osteoporosis Quality of Life). Results: Approximately 50% of patients had osteoporosis, with a prevalence of vertebral fractures of 65.5%. In most patients, we found hypovitaminosis D and high levels of parathyroid hormone (PTH). Furthermore, a statistically significant association was observed between high PTH levels and previous lymphoma treatment. Finally, the MiniOsteoporosis Quality of life (mini-OQLQ) questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status. Conclusions: Patient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients

Total dietary antioxidant capacity and lung function in an Italian population: a favorable role in premenopausal/never smoker women

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Epigenetic signatures of internal migration in Italy.

Observational studies have suggested that the risks of non-communicable diseases in voluntary migrants become similar to those in the host population after one or more generations, supporting the hypothesis that these diseases have a predominantly environmental (rather than inherited) origin. However, no study has been conducted thus far to identify alterations at the molecular level that might mediate these changes in disease risk after migration