Stress oxidative and genotoxicity in Prochilodus lineatus (Valenciennes, 1836) exposed to commercial formulation of insecticide cypermethrin.

The use of toxic pesticides has become a world problem because they can contaminate streams and rivers, producing an adverse impact on non-target aquatic biota, including fishes. Cypermethrin is one of the most important insecticides to control ectoparasites in wide-scale. The aim of this study was to evaluate the effect of commercial formulations of cypermethrin, SHERPA O (0.0, 0.075, 0.15, and 0.3 µg/L of cypermethrin) in fish Prochilodus lineatus for 96 h in semi-static condition, using biomarkers of genotoxicity: micronucleus frequency (MNF) in erythrocytes and biomarkers of oxidative damage: lipid peroxidation (TBARS) and antioxidant defenses, catalase (CAT) and glutathione (GSH) in liver tissue. Our results showed a significant decrease (p < 0.05) of CAT at pesticide concentrations of 0.150 and 0.300 µg/L, but no significant difference was observed in TBARS or GSH in any exposed group (p > 0.05) in comparison to the control. A significant increase was observed in the MNF in the group exposed to 0.3 µg/L of cypermethrin compared to negative control (p < 0.05). Finally, P. lineatus proved to be a sensitive species to the commercial formulations of cypermethrin and that CAT and MNF are effective indicators of these toxic effects.

Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study.

BACKGROUND: Allogeneic stem-cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT. PATIENTS AND METHODS: We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML). After a median of four cycles (range 1-11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and 22% progressive disease. Ten patients discontinued treatment before the planned four cycles, due to an adverse event in nine cases. RESULTS: A HSC donor was identified in 73 patients, and HSCT was performed in 54 patients (74% of patients with a donor). Main reasons for turning down HSCT were lack of a donor, an adverse event, or progressive disease (9, 12, and 16 patients, respectively). At a median follow-up of 20.5 months from enrolment, response to AZA was the only independent prognostic factor for survival. Compared to baseline assessment, AZA treatment did not affect patients' comorbidities at HSCT: the HCT-CI remained stable in 62% patients, and worsened or improved in 23% and 15% of patients, respectively. CONCLUSIONS: Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be 'bridged' using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS. The trial has been registered with the EudraCT number 2010-019673-1.

Sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy.

OBJECTIVE: To investigate the effects of fractional microablative CO2 laser on sexual function and overall satisfaction with sexual life in postmenopausal women with vulvovaginal atrophy (VVA). METHOD: This prospective study included 77 postmenopausal women (mean age 60.6 ± 6.2 years) treated for VVA symptoms with the fractional microablative CO2 laser system (SmartXide(2) V(2)LR, Monalisa Touch, DEKA, Florence, Italy). Sexual function and quality of life were evaluated with the Female Sexual Function Index (FSFI) and the Short Form 12 (SF-12), respectively, both at baseline and at 12-week follow-up. A 10-mm visual analog scale was used to measure the overall satisfaction with sexual life and the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia and dysuria) before and after the study period. RESULTS: We observed a significant improvement in the total score and the scores in each specific domain of the FSFI at 12-week follow-up compared to baseline (p < 0.001). After concluding the laser treatment, the overall satisfaction with sexual life significantly improved (p < 0.001). Seventeen (85%) out of 20 (26%) women, not sexually active because of VVA severity at baseline, regained a normal sexual life at the 12-week follow-up. Finally, we also found a significant improvement in each VVA symptom (p < 0.001) and in quality-of-life evaluation, both for the scores in the physical (p = 0.013) and mental (p = 0.002) domains. CONCLUSIONS: Fractional microablative CO2 laser treatment is associated with a significant improvement of sexual function and satisfaction with sexual life in postmenopausal women with VVA symptoms.

An alternative approach for the treatment of vaginal atrophy.

AIM: The aim of this study was to determine the efficacy of a new topic non-hormonal treatment for postmenopausal women complaining of symptoms of vaginal atrophy. METHODS: Patients included in the study were prescribed Sinecol gel (AM PHARMA Srl, Vimercate, Monza and Brianza, Italy) application once a day for 20 consecutive days. Sinecol gel is a topic compound for vaginal atrophy containing hyaluronic acid, that is known to improve vaginal elasticity, lactoperoxidase, Xantham gum and glucose oxidase, which have protective and antibacterial action. We evaluated each patient before and after treatment, both subjectively with the "Visual Analogical Scale" (VAS) and objectively with the "Vaginal Health Index" (VHI). RESULTS: We observed a significant clinical improvement of the subjective and objective assessment of symptoms severity with a p value <0.001 at the end of the treatment compared to baseline. CONCLUSION: Sinecol gel appears to be an effective and valid non-hormonal alternative to the estrogen therapy for vaginal atrophy.

Comet assay in gill cells of Prochilodus lineatus exposed in vivo to cypermethrin.

Agricultural chemicals can induce genetic alterations on aquatic organisms that have been associated with effects on growth, reproduction and population dynamics. The evaluation of DNA damage in fish using the comet assay (CA) frequently involves the utilization of erythrocytes. However, epithelial gill cells (EGC) can be more sensitive, as they are constantly dividing and in direct contact with potentially stressing compounds from the aquatic environment. The aim of the present study was to evaluate (1) the sensitivity and suitability of epithelial gill cells of Prochilodus lineatus in response to different genotoxic agents through the application of the CA, (2) the induction of DNA damage in this cell population after in vivo exposure to cypermethrin. Baseline value of the CA damage index (DI) for EGC of juvenile P. lineatus was 144.68±5.69. Damage increased in a dose-dependent manner after in vitro exposure of EGC to methyl methanesulfonate (MMS) and H2O2, two known genotoxic agents. In vivo exposure of fish to cypermethrin induced a significant increase in DNA DI of EGC at 0.150µg/l (DI: 239.62±6.21) and 0.300µg/l (270.63±2.09) compared to control (150.25±4.38) but no effect was observed at 0.075µg/l (168.50±10.77). This study shows that EGC of this species are sensitive for the application of the CA, demonstrating DNA damage in response to alkylation (MMS), oxidative damage (H2O2), and to the insecticide cypermethryn. These data, together with our previous study on DNA damage induction on erythrocytes of this species, provides useful information for future work involving biomonitoring in regions where P. lineatus is naturally exposed to pesticides and other genotoxic agents.

The role of vaginal Lactobacillus Rhamnosus (Normogin®) in preventing Bacterial Vaginosis in women with history of recurrences, undergoing surgical menopause: a prospective pilot study.

BACKGROUND: Bacterial vaginosis (BV), a poly-microbial clinical syndrome, is the most common cause of vaginal symptoms among women. The recurrence rate of BV is up to 30% after traditional antimicrobial therapy. Lactobacillus rhamnosus vaginal tablets have demonstrated to be a reliable topical effective and safe treatment to reduce the BV recurrence rate. AIM: to assess topical long-lasting (6 months) Lactobacillus rhamnosus effectiveness in decreasing recurrences in women with positive anamnesis of recurrent BV and concomitant hypo-estrogenism as consequence of surgical menopause. PATIENTS AND METHODS: A total of 22 consecutive patients affected by recurrent BV and treated for surgical menopause for benign pathology were enrolled. All women were treated with Lactobacillus rhamnosus vaginal tablets (Normogin(®)) according to the following protocol: 1 tablet/day for 6 days, than two tablets per week for 2 months and then one tablet once a week till 6 months. RESULTS: Of the 22 women enrolled only one has been lost after the first visit. A total of 21 cases were reported; 7 out of 21 had only one case of recurrence, while 2 out of 21 had two episodes of BV during the year successive to menopause. No side effects have been reported. CONCLUSIONS: Considering the low recurrence rate of BV during follow-up it seems that long-lasting treatment with vaginal tablets of Lactobacillus rhamnosus could reduce the BV recurrence also in women at high risk with positive history of pathology and undergoing surgical menopause with a safe profile. This study supports the use of vaginal Lactobacillus rhamnosus administration in high risk population without side effects.

Development of JAK2V617F-positive polycythemia vera after chemotherapy-induced remission of primary central nervous system diffuse large B cell non-Hodgkin's lymphoma: a case report and review of the literature.

The coexistence or the development of Philadelphia chromosome-negative myeloproliferative neoplasms after a lymphoproliferative disease in the same patient is an extremely rare event. We report the case of a 72-year-old man who developed JAK2V617F polycythemia vera 3 years after the diagnosis and treatment of primary diffuse large B cell non-Hodgkin's lymphoma of the central nervous system. We also review the literature regarding the pathogenesis underlying the association of myeloproliferative and lymphoproliferative chronic disorders.

Hepatic enzymes activity in the fish Prochilodus lineatus (Valenciennes, 1836) after sublethal cypermethrin exposure.

Prochilodus lineatus, a fish, was exposed to sublethal concentrations of cypermethrin: 0.075, 0.150, and 0.300 µg L(-1) and a control group (without cypermethrin) for 96 h. Five specimens were exposed in each concentration for triplicate (n = 60). Hepatic biochemical values and behavioral changes were studied. The results revealed a significantly higher level of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in hepatic tissue at different concentrations of cypermethrin tested compared to control (p < 0.05). A decrease in total protein was observed in exposed groups but not significantly (p > 0.05). This study provides information to know toxic mechanisms of cypermethrin on hepatic enzymes of P. lineatus that are poorly understood.

BCR and BCR-ABL regulation during myeloid differentiation in healthy donors and in chronic phase/blast crisis CML patients.

Chronic myeloid leukemia (CML) is caused by the BCR-ABL hybrid gene. The molecular mechanisms leading from chronic phase (CP) to blast crisis (BC) are not understood. However, both the presence and the levels of BCR-ABL seem to be important for CML progression. BCR-ABL is under the transcriptional control of BCR promoter. Here we focused on the gene expression control of BCR and BCR-ABL upon myeloid differentiation in healthy donors (HDs), CP and BC patients. As previously reported, BCR-ABL is downregulated during myeloid maturation in CP patients. A similar pattern was detected for BCR (but not for ABL) in CP-CML and in HD, thus suggesting that the two genes may be under a similar transcriptional control. In BC this mechanism is similarly impaired for both BCR-ABL and BCR. These data indicate the presence of an 'in trans' deregulated transcription of both BCR and BCR-ABL promoters, associated with CML progression.

Dermal lip protuberances associated with aquatic surface respiration in juveniles of the piscivorous characid Salminus brasiliensis (Actinopterygii: Characidae)

Some South American freshwater fishes can improve their capability of aquatic surface respiration (ASR) by developing dermal lip protuberances in the lower jaw. This adaptation was thought to be limited to omnivorous or herbivorous fishes. The present work provides the first evidence that juveniles of a piscivorous characid, Salminus brasiliensis, develop dermal lip protuberances during periods of hypoxia in floodplain ponds of the Salado River, in Argentina. The protuberance of S. brasiliensis involves dermal portions of both jaws exhibiting lateral lobes on the sides of the mouth arranged in the vertical plane. Water dissolved oxygen concentrations less than or equal to 1.05 mgl-1 were associated with a remarkable increase in lip protuberance. The lateral lobes of the protuberance in this species may limit the access of water to the anterior portion of the mouth which is positioned nearer to the oxygenated surface water during ASR. Finally, ASR, complemented with the development of dermal lip protuberances, can be considered a valuable strategy to survive in hypoxic environments, even for carnivorous fishes with elevated oxygen requirements.(AU)

Alguns peixes de água doce da América do Sul podem melhorar o desempenho da respiração aquática superficial (RAS) desenvolvendo protuberâncias dérmicas labiais na mandíbula. Considerava-se que essa adaptação era limitada aos peixes onívoros ou herbívoros. Este trabalho apresenta os primeiros indícios de que juvenis de um caracídeo piscívoro, Salminus brasiliensis, desenvolvem protuberâncias dérmicas labiais durante períodos de hipoxia em lagoas de várzea do rio Salado, Argentina. As protuberâncias de S. brasiliensis envolvem porções dérmicas das duas mandíbulas e exibem lóbulos laterais ao lado da boca dispostas no plano vertical. Concentrações de oxigênio dissolvido na água, inferiores ou iguais a 1,05 mgl-1, foram associadas a um aumento notável no desenvolvimento das protuberâncias labiais. Nesta espécie os lóbulos laterais da protuberância podem limitar o acesso de água à porção anterior da boca, que está posicionada mais perto da superfície da água oxigenada durante a RAS. Finalmente, a RAS, complementada com o desenvolvimento de protuberâncias dérmicas labiais, pode ser considerada uma valiosa estratégia para a sobrevivência em ambientes hipóxicos, mesmo para peixes carnívoros com elevada demanda de oxigênio.(AU)

Alkaline comet assay for genotoxic effect detection in neotropical fish Prochilodus lineatus (Pisces, Curimatidae).

Toxicants on fish may induce genetic alterations that can be used as genotoxic markers. We evaluated DNA damage using alkaline comet assay applied on erythrocytes after in vivo exposure of Prochilodus lineatus to different concentrations of Cypermethrin (0.300, 0.150, 0.075 and 0.000 microg/L) as a probable chemical mutagen. The results revealed a significantly higher level of DNA damage at all concentrations of Cypermethrin tested compared to control and background level (p < 0.05). We have standardized the technique for one of the most common native fish species that will be useful for biomonitoring genotoxicity in polluted waters of the region.

Changes of hematological parameters in Prochilodus lineatus (Pisces, Prochilodontidae) exposed to sublethal concentration of cypermethrin.

Freshwater fish Prochilodus lineatus were exposed to sublethal concentrations of cypermethrin (0.3 and 0.6 microg/l) for 2, 5 and 8 days. It was observed that with the increase of exposure time total erythrocyte (RBC), hemoglobin (Hb), hematocrit (Ht) and mean corpuscular hemoglobin concentration (MCHC) values decreased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values increased. These reports indicate that hematological parameters, may be useful as a diagnostic test for cypermethrin exposure in aquatic organisms.

Successful treatment with T-depleted autologous peripheral blood stem cell transplantation of refractory chronic autoimmune thrombocytopenic purpura.

Autoimmune thrombocytopenia (AITP) is a disorder due to specific platelet auto-antibodies directed against platelet surface glycoproteins. AITP in adults is usually chronic, idiopathic and frequently refractory to conventional treatments. Myelo- and immuno-suppressive chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation is an experimental approach for severe chronic refractory AITP. We report a case of a woman with AITP, refractory to the conventional therapy, submitted to T-cell-depleted autologous PBSC transplantation, which obtained long term stable response on platelet count. We deem that the positive outcome of our patient depends on T-cells depletion of the graft, which reduces autoreactive T clones.

Cytomegalovirus infection after autologous stem cell transplantation: incidence and outcome in a group of patients undergoing a surveillance program.

This study was performed to evaluate the incidence, risk factors, and outcome of cytomegalovirus (CMV) infection in autologous stem cell transplantation (ASCT), with the aim of performing preemptive therapy in patients with antigenemia. Starting from 2001, 171 consecutive ASCTs were performed in 136 patients; 102 of these patients were seropositive for CMV at the onset of hematological disease. In all these patients, a CMV pp65 antigenemia assay was determined weekly, starting from the day when the absolute neutrophil count went above 500/microL, and until day 60 after ASCT; subsequently, antigenemia was determined only when a CMV infection was suspected. Among the 136 transplanted patients, 40 (29.4%) presented a positive antigenemia; all of them were seropositive for CMV before ASCT; and no cases of primary infection were seen. The incidence of CMV infection in the seropositive population was 40/102 (39.3%); 6 patients (5 with multiple myeloma and 1 with non-Hodgkin's lymphoma) who received 2 ASCTs developed CMV infections after both transplantations, so that positive antigenemia developed after 46/171 (26.9%) transplantations. First positive antigenemia presented a median of 32 days (range 7-57) after stem cell reinfusion. The median antigenemia level at the first appearance was 2/200,000 (range 1-1000). No significant prognostic factors could be shown. Enteritis was present in 5 patients; 2 of them also had fever, and 1 of them also had thrombocytopenia. In 5 patients fever without any other clinical signs or symptoms was present; 30 patients were asymptomatic. Fourteen patients were treated with anti-CMV drugs. CMV reactivation was successfully treated in all patients, and no patient died from CMV disease.

Immune reactivity during the growth of a murine lung adenocarcinoma: evaluation of paraneoplastic syndrome development.

The purpose of this study was to investigate if specific immune responses were present in mice bearing a lung adenocarcinoma that presents paraneoplastic syndromes during tumor evolution. Leukocytosis, mainly due to polymorphonuclear leukocytes, was found from day 15 of tumor growth. Delayed type hypersensitivity response and increased interleukin-6 (IL-6) serum levels were observed along tumor growth. Concomitant immunity, specific rejection of a second inoculum and in vitro specific cytotoxicity occurred at 20 days of implant. In advanced stages of tumor evolution impaired cytotoxicity, accompanied by a great increase of IL-6 in serum, were observed. Role of polymorphonuclear leukocytes and IL-6 overproduction as responsible for immune dysregulation and paraneoplastic syndromes are discussed.

Defibrotide in recurrent thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a common illness characterized by platelet thrombi within the microvascularization. In its natural course, this disease has had a mortality rate of 90%. Plasma infusion or exchange achieved a survival rate of 70% to 90%. However, 10% to 30% of patients surviving the initial TTP episode relapse at regular intervals. The treatment of recurrent forms of the disease remains a challenge; several approaches have been shown to induce medium to long term remissions. We describe a patient with recurrent TTP whose disease remitted after administration of defibrotide.

Mechanisms of paraneoplastic syndromes in mice bearing a spontaneous lung adenocarcinoma.

Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.