A 6 day course of liposomal amphotericin B in the treatment of infantile visceral leishmaniasis: the Italian experience

OBJECTIVES: To evaluate in a retrospective analysis the efficacy and safety of a 6 day course of liposomal amphotericin B (L-AmB) in infantile cases of Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in Italy. PATIENTS AND METHODS: Patients included were diagnosed as having VL consecutively admitted from December 1992 to December 2001 at four main referral children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L-AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data, nutritional status, underlying diseases, clinical and laboratory findings, and therapy outcome were considered. RESULTS: A total of 164 HIV-negative children (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients were initially cured by the given treatment, and did not present adverse events related to drug infusion. Seven patients (4.3%) had a clinical and parasitological relapse 3-15 months after therapy. All relapses were successfully retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg). CONCLUSIONS: This study highlights the efficacy (>95%) and safety of the six dose L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in children

Pneumocystis cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells

<p>Abstract</p> <p>Background</p> <p>Respiratory failure secondary to alveolar inflammation during <it>Pneumocystis </it>pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with <it>Pneumocystis </it>infection predicts severity of the infection and death. Several previous studies indicate that airway epithelial cells release the neutrophil chemoattractant proteins, MIP-2 (rodents) and IL-8 (humans), in response to <it>Pneumocystis </it>and purified <it>Pneumocystis </it>cell wall β-glucans (PCBG) through the NF-κB-dependent pathway. However, little is known about the molecular mechanisms that are involved in the activation of airway epithelium cells by PCBG resulting in the secretion of IL-8.</p> <p>Method</p> <p>To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo^-cells, a human airway epithelial cell line.</p> <p>Results</p> <p>Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-κB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for β-glucans in human airway epithelial cells. Preincubation of the cells with D-<it>threo</it>-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) a potent inhibitor of the glycosphingolipids synthesis, prior to PCBG stimulation, significantly decreased IL-8 production.</p> <p>Conclusion</p> <p>These data indicate that PCBG activates calcium dependent MAPK signaling resulting in the release of IL-8 in a process that requires glycosphingolipid for optimal signaling.</p

Impaired contractile function of the supraspinatus in the acute period following a rotator cuff tear

Background: Rotator cuff (RTC) tears are a common clinical problem resulting in adverse changes to the muscle, but there is limited information comparing histopathology to contractile function. This study assessed supraspinatus force and susceptibility to injury in the rat model of RTC tear, and compared these functional changes to histopathology of the muscle. Methods: Unilateral RTC tears were induced in male rats via tenotomy of the supraspinatus and infraspinatus. Maximal tetanic force and susceptibility to injury of the supraspinatus muscle were measured in vivo at day 2 and day 15 after tenotomy. Supraspinatus muscles were weighed and harvested for histologic analysis of the neuromuscular junction (NMJ), intramuscular lipid, and collagen. Results: Tenotomy resulted in eventual atrophy and weakness. Despite no loss in muscle mass at day 2 there was a 30% reduction in contractile force, and a decrease in NMJ continuity and size. Reduced force persisted at day 15, a time point when muscle atrophy was evident but NMJ morphology was restored. At day 15, torn muscles had decreased collagen-packing density and were also more susceptible to contraction-induced injury. Conclusion: Muscle size and histopathology are not direct indicators of overall RTC contractile health. Changes in NMJ morphology and collagen organization were associated with changes in contractile function and thus may play a role in response to injury. Although our findings are limited to the acute phase after a RTC tear, the most salient finding is that RTC tenotomy results in increased susceptibility to injury of the supraspinatus

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure

<p>Abstract</p> <p>Background</p> <p><it>Pneumocystis spp</it>. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. <it>Pneumocystis </it>colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to <it>Pneumocystis</it>.</p> <p>Methods</p> <p>To analyze the role of SP-A in protecting the immunocompetent host from <it>Pneumocystis </it>colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to <it>P. murina </it>colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Detection of <it>P. murina </it>specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to <it>P. murina </it>within the animal facility. However, P. <it>murina </it>mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, <it>P. murina </it>cyst forms were also only detected in KO mice. <it>P. murina </it>mRNA was detected in <it>SCID </it>mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.</p> <p>Conclusion</p> <p>These data support an important role for SP-A in protecting the immunocompetent host from <it>P. murina </it>colonization, and provide a model to study <it>Pneumocystis </it>colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to <it>P. murina </it>even when housed under barrier conditions.</p

Pathways towards coexistence with large carnivores in production systems

Coexistence between livestock grazing and carnivores in rangelands is a major challenge in terms of sustainable agriculture, animal welfare, species conservation and ecosystem function. Many effective non-lethal tools exist to protect livestock from predation, yet their adoption remains limited. Using a social-ecological transformations framework, we present two qualitative models that depict transformative change in rangelands grazing. Developed through participatory processes with stakeholders from South Africa and the United States of America, the models articulate drivers of change and the essential pathways to transition from routine lethal management of carnivores towards mutually beneficial coexistence. The pathways define broad actions that incorporate multiple values in grazing systems including changes to livestock management practices, financial support, industry capacity building, research, improved governance and marketing initiatives. A key fnding is the new concept of ‘Predator Smart Farming’, a holistic and conscientious approach to agriculture, which increases the resilience of landscapes, animals (domesticated and wild) and rural livelihoods. Implementation of these multiple pathways would lead to a future system that ensures thriving agricultural communities, secure livelihoods, reduced violence toward animals, and landscapes that are productive and support species conservation and coexistence

Improved survival of children with neuroblastoma between 1979 and 2005: a report of the Italian Neuroblastoma Registry

Purpose To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. Patiens and Methods The study includes data from 2.216 children(age 0 to 14 years)diagnosed between 1979 and 2005. Overal survival (OS) was analyzed by clinical and biologic featurres at presentation and periods of diagnosis:1979 to 1984, 1985 to 1991, 1992 to 1998 and 1999 to 2005. The relative risk of second malignant neoplasm (SMN)was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. Results Yearly patient accrual increased over time from 58 to 102: Patients age 0 to 17 months represented 45,6% of the total population, and their incidence increased over time from 36,5% to 48,5%. The incidence of stage 1 patients increased over time from 5,8% to 23,2%. A total of 898 patients (40,5%) developed disease progression or relapse, 19 patients developed SMN, and two patientes developed myelodysplasia, The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8,4% (95% CI,5.1 to 13.2. A total of 858 patients (39%) died (779) of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications): Ten-year OS was 56,3% (95% CI, 53.0% to 57.6%) and incresed over time from 34,9% to 65,0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%) , but not afterward. Conclusion The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN

Consumo de álcool entre estudantes universitários Alcohol consumption by university students

O consumo de álcool é estimulado pela mídia apesar dos riscos inerentes à saúde. Estudantes da área de saúde serão os futuros profissionais a orientar a população ou servir de exemplo. O objetivo deste estudo foi analisar o consumo de álcool e fatores relacionados nestes estudantes. Participaram 608 estudantes universitários de Maceió, Alagoas, Brasil, de ambos os sexos, mediante a aplicação de um questionário autopreenchível. Foram empregados modelos de regressão de Poisson e logística multinomial. A prevalência de uso na vida de álcool foi de 90,4%. O abuso de álcool teve uma prevalência de 18,3% nos homens e 6,1% nas mulheres. Os que apresentaram maior consumo e abuso de álcool foram os do sexo masculino, de maior idade, naturais de outras cidades, fumantes e os expostos à publicidade do álcool. Os resultados deste estudo indicam uma vulnerabilidade destes jovens para condutas com risco para a saúde. Seu papel social futuro suscita necessidades distintas de formação universitária para que possam atuar profissionalmente nesta área.<br>Consumption of alcoholic beverages is widely encouraged by the mass media, despite the related health risks. Today's students in the health fields are the professionals of tomorrow who will be providing advice and serving as role models for patients. The aim of this study was to analyze alcohol consumption and related factors among these students. A total of 608 male and female university students from Maceió, the capital of Alagoas State, Brazil, completed a self-administered questionnaire. Data analysis included Poisson regression and multinomial logistic models. Prevalence of lifetime use of alcohol was 90.4%. Prevalence of alcohol abuse was 18.3% in men and 6.1% in women. Heavier alcohol consumption and alcohol abuse were observed in males, older students, non-natives of Maceió, smokers, and those exposed to alcohol advertising. The results emphasized the vulnerability of these young people to risky health behaviors. Their future social role highlights distinct needs in their university education to enable them to act professionally in this area