Dysgeusia increases the risk for death and other side effects during antineoplastic systemic treatment for solid tumors: a cross-sectional study.

BACKGROUND: Chemotherapy (QT) is a systemic treatment using a combination of antineoplastic drugs, orally or intravenously, that inhibit tumor growth and fast-growing normal cells. Due to its nonspecificity, chemotherapy can cause a series of adverse effects, such as altered taste (dysgeusia), associated with malnutrition and, consequently, other adverse effects in the gastrointestinal tract and increased mortality risk. This study aimed to evaluate the influence of dysgeusia on the incidence of other adverse effects and overall survival during antineoplastic chemotherapy (chemotherapy). MATERIAL AND METHODS: An observational, retrospective, cross-sectional study was conducted using data from the Electronic Health Record system of the Cancer Institute of Ceará over two years. Before the CT session, the multi-professional team evaluated the patient for the presence and severity of adverse effects (AE), using scores from the CTCAE v5.0 scale. Dysgeusia scores were collected and associated with clinical pathological data, with other adverse effects (nausea, vomiting, diarrhea, oral mucositis, anorexia, constipation), and with overall survival. Chi-square and Mantel-Cox log-rank tests were used. RESULTS: Of 5744 patients evaluated, dysgeusia presented a frequency of 50.6%, being directly associated with female gender (p=0.001), overweight (p=0.022), high tumor stages (p=0.009), a combination of adjuvant and neoadjuvant (p=0.010) and four-year survival (p=0.030). Dysgeusia frequency was directly associated with diarrhea (p<0.001), anorexia (p<0.001), oral mucositis (p<0.001), nausea (p<0.001), constipation (p<0.001) and vomiting (p<0.001), and inversely associated with fatigue (p=0.035). CONCLUSIONS: Dysgeusia during CT increases the risk of other adverse effects and negatively impacts prognosis.

Comparison of a daily and alternate-day photobiomodulation protocol in the prevention of oral mucositis in patients undergoing radiochemotherapy for oral cancer: a triple-blind, controlled clinical trial.

BACKGROUND: Preventive Photobiomodulation Therapy (PBMT) significantly reduces oral mucositis (OM) severity in patients undergoing Radiochemotherapy (RCT) for the treatment of oral cancer, but daily applications generate cost, overload the dental team, and reduce the number of patients assisted.To evaluate the effectiveness of two PBMT protocols in preventing OM in patients undergoing RCT for oral cancer. MATERIAL AND METHODS: 16 patients diagnosed with oral cancer undergoing RCT were included, equally divided into two groups: a group treated daily with PBMT, and another group also submitted to daily treatment, however, performing the application of PBMT every three days, interspersed with a simulation of PBMT (placebo). A red laser was used (~660 nm), 0.1W power, 1J of energy applied per point, 9 points per area (labial mucosa, buccal mucosa, lateral borders of the tongue, body of the tongue, and floor of the mouth) from the beginning of RCT until the end of the oncological treatment. Daily assessments were performed regarding OM scores, the World Health Organization (WHO) pain scale, and the visual analog scale (VAS). Weight, salivary flow (SGAPP), OHIP-14, and DMFT were evaluated on the initial and final days of RT. OM incidence and clinical data were compared by Pearson's chi-square test or Fisher's exact test. Pain and other scale scores were compared using the Mann-Whitney and Friedman/Dunn tests (SPSS v20.0 p<0.05). RESULTS: In the group with PBMT on alternate days, there was an increase in the frequency of grade 2 and grade 3 oral mucositis and an increased risk of grade 2 oral mucositis, in addition to higher mean pain scores and greater reduction in salivary flow. CONCLUSIONS: The daily PBMT protocol proved more effective in controlling the frequency and severity of OM, pain, and salivary flow.

Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Malignant salivary gland tumors: agreement between fine needle aspiration biopsy, incisional biopsy and final histopathological diagnostic.

BACKGROUND: Incisional biopsy is indicated for intraoral tumors, but it is a contraindicated surgical procedure for major salivary glands. To avoid complications and facilitate diagnosis, fine needle aspiration biopsy (FNAB) is a type of biopsy widely used for preoperative diagnosis in these glands. MATERIAL AND METHODS: The aim of this study was to analyze the agreement between the diagnosis by FNAB (major glands), incisional biopsy (minor glands) and histopathological analysis of the surgical specimen in salivary gland tumors from a database (medical records) of patients treated in a cancer treatment reference center in the Northeast region of Brazil. RESULTS: The sample consisted of 110 cases, being 86 of them malignant tumors in major salivary glands (parotid gland=73; submandibular gland=13) and 24 cases in minor salivary glands (palate). The female gender was the most affected (57.3%), especially in patients over 60 years (42.7%). In the TNM classification, 41.8% of the cases were in T2 at the time of diagnosis, with most of the regional lymph nodes in N0 (85.5%) and 87.3% of the cases in M0. FNAB was able to identify malignant neoplasms in 68.6% of the cases (n=59), while incisional biopsy in palatal tumors obtained agreement of 75% of the cases (n=18). The analysis revealed that tumors classified as T3-T4 (p=0.012) showed greater agreement between pre- and post-surgical diagnosis. CONCLUSIONS: The results obtained in this study indicate that FNAB has similar accuracy to incisional biopsy in providing satisfactory preoperative diagnoses of malignant tumors in salivary glands.

Risk factors for oral mucositis during chemotherapy treatment for solid tumors: a retrospective STROBE-guided study.

BACKGROUND: This study retrospectively analyzed the risk factors for transchemotherapy oral mucositis (OM). MATERIAL AND METHODS: Before each chemotherapy cycle, patients were routinely evaluated for the presence/severity of OM based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded as follows: However, specific conditions such as mucositis are graded on a five-point scale: 0, absence of mucositis, grade 1 (Asymptomatic or mild), 2 (Presence of pain and moderate ulceration, without interference with food intake), 3 (severe pain with interference with food intake) or 4 (Life-threatening with the need for urgent intervention). Information from 2 years of evaluations was collected and patient medical records were reviewed to obtain data on chemotherapy cycle, sex, age, body mass index, body surface area, primary tumor, chemotherapy protocol, and history of head and neck radiotherapy. The X² test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p<0.05). RESULTS: Among 19,000 total evaluations of 3,529 patients during 5.32±4.7 chemotherapy cycles (CT) the prevalence of OM was 6.3% (n=1,195). Chemotherapy duration (p<0.001), female sex (p=0.001), adjuvant intention (p=0.008) and the use of carboplatin (p=0.001), cisplatin (p=0.029), docetaxel (p<0.001) and bevacizumab (p=0.026) independently increased the risk of mucositis. In head and neck tumors, 2018 year (p=0.017), chemotherapy duration (p=0.018), BMI>30 (p=0.008), radiotherapy (p=0.037) and use of carboplatin (p=0.046) and cyclophosphamide (p=0.010) increased this prevalence. CONCLUSIONS: Cycles of chemotherapy, sex, cytotoxicity drugs, bevacizumab and head and neck radiotherapy increase the risk of OM in solid tumors.

Excess mortality in depressive and anxiety disorders: The Lifelines Cohort Study.

BACKGROUND: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status. METHODS: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models. RESULTS: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty). CONCLUSIONS: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

Incidence and profile of benign epithelial tumors of salivary glands from a single center in Northeast of Brazil.

BACKGROUND: Benign tumors of the salivary glands are a group of lesions with varied histopathological and clinical spectrum. The aim was to determine the incidence and clinicopathological characteristics of benign salivary gland neoplasms diagnosed between 2007 and 2016 in a single center located in northeastern Brazil. MATERIAL AND METHODS: Records regarding sex, age, anatomical location, histopathological subtype and treatment were retrieved, and data were analyzed using the Stata/IC software (version 12.0). RESULTS: There were above 7,100 cases of neoplasms in the head and neck region, of which 403 corresponded to salivary gland neoplasms. Of these, 238 (59%) were benign, being pleomorphic adenoma (PA) the most frequent neoplasm (n=178; 74.8%), followed by Warthin's tumor (WT) (n=23; 9.7%). Overall, most cases occurred in females (n=136; 57.1%) and age ranged from 11 to 83 years. The parotid gland (n=188; 79%) was the most common anatomical site, and all patients were treated by surgical excision. Of the cases diagnosed as PA, malignant transformation to carcinoma ex-pleomorphic adenoma (CAEXPA) occurred in 7 (3.9%) cases. CONCLUSIONS: The present study confirmed the clinical and demographic profile of benign salivary gland neoplasms, which contributes to the continuous knowledge of current data about these lesions.

Clinical-pathological and sociodemographic factors associated with the distant metastasis and overall survival of oral cavity and oropharynx squamous cell carcinoma.

BACKGROUND: The objective of this study was to evaluate the influence of clinical-pathological and sociodemographic factors on the prevalence of distant metastasis (DM) and overall survival in patients with oral cavity and oropharynx squamous cell carcinoma (OOSCC). MATERIAL AND METHODS: Cross-sectional study based on the records of 404 OOSCC patients evaluated for DM, covering the period 2000-2014. We analysed the influence of age, sex, level of schooling, primary tumor subsite, treatment, marital status, family history of cancer, history of smoking and alcohol consumption, type of health care coverage (private vs. public) and overall survival. Findings were submitted to Fisher's exact test, Pearson's chi-squared test, Mantel-Cox log-rank testing and multinomial and Cox regression analysis (SPSS v. 20.0; p<0.05). RESULTS: The prevalence of DM was 5.4% (22/404). The respiratory tract was the most affected DM site (n=9; 40.9%). Male sex (p=0.049), oropharyngeal primary tumor (p=0.008), stage T3-4 (p=0.022), lymph node metastasis (N+) (p<0.001) and palliative treatment (p=0.005) were directly associated with DM. Patients with oral primary tumours (p=0.343) and primary oropharyngeal tumours (p=0.242) did not differ significantly with regard to the prevalence of DM. N+ was an independent risk factor for DM (p=0.017). Five variables independently reduced overall survival: male sex (p=0.035), age >65 years (p=0.046), indigenous/brown racial type (p=0.045), palliative treatment (p=0.035) and DM (p=0.048). CONCLUSIONS: Lymph node metastasis independently increased the prevalence of DM and, along with male sex, older age, brown racial type and palliative treatment, was independently associated with poor prognosis in patients with OOSCC.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Interactions between lifestyle and MTHFR polymorphisms on homocysteine concentrations in young adults belonging to the 1982 Pelotas Birth Cohort.

BACKGROUND/OBJECTIVES: Homocysteine (Hcy) is a key intermediate in methionine metabolism. A high plasma concentration of Hcy is an independent risk factor for cardiovascular diseases among other determinants. In this study, we aimed to investigate the interactions between methylenetetrahydrofolate reductase enzyme gene (MTHFR) polymorphisms and lifestyle variables (smoking, alcohol intake and physical activity) on Hcy concentrations in a young Brazilian population. SUBJECTS/METHODS: The study population comprised 3803 individuals from the Pelotas Birth Cohort, aged 22-23 years. Allelic discrimination assays and chemiluminescence immunoassays were performed for genotyping and serum Hcy measurements, respectively. Linear regression models were used to explore the effect of gene-lifestyle interactions on Hcy concentrations. RESULTS: Men carrying the MTHFR 677TT genotype, who were also smokers and drinkers (⩾15 g of alcohol per day), had the highest concentration of Hcy (P-value for the interaction <0.001 for smoking and 0.002 for alcohol intake). In contrast, high folate concentrations attenuated the effects of the MTHFR C677T genotype on serum Hcy concentrations (P-value for interaction <0.001). Also, among males, blood folate concentration was the only lifestyle variable able to modify the influence of MTHFR A1298C genotypes on Hcy concentrations (P-value for the interaction <0.001). There was no strong evidence of an interaction between the MTHFR genotypes and the lifestyle variables in women. CONCLUSIONS: In summary, our study demonstrates a sex difference in Hcy concentrations among Brazilian young adults regarding MTHFR C677T-lifestyle interactions that are worsened under conditions of low blood folate. Identification of potentially modifiable factors related to an increase in homocysteine in young adults, especially in those who are genetically susceptible, is important to prevent negative health consequences in the future.

Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity.

Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be cofactors for other clinically relevant conditions, especially food-dependent exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is required for the correct diagnosis, classification, and treatment of affected patients.

Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.

Fungi associated to musca domestica captured with traps containing chemical bait and by direct search / Fungos associados à Musca Domestica capturadas através de armadilhas com isca química e busca direta

This study evaluated the isolation of fungi from Musca domestica captured through direct search and chemical baits and also the influence of chemical bait for the growth of fungi found on these flies. Collection using traps with chemical bait, composed of the insecticide Imidacloprid, and a direct search were carried out. It was verified that 71.73% of the flies collected from the direct search presented fungi growth, whereas only 28.26% of the flies captured using chemical bait showed fungi growth. In the test carried out with the addition of chemical bait to the BDA media culture, fungal growth was not observed. For studies of fungi resident on M. domestica, the use of the insecticide Imidacloprid with chemical bait is not recommended, as this product can inhibit some microorganisms, including potential biocontrols for M. domestica.

Este trabalho avaliou o isolamento de fungos em Musca domestica através da busca direta e por meio de iscas químicas e também a influência desta isca química para o crescimento de fungos encontrados nessas moscas. Foram realizadas coletas usando armadilhas com iscas químicas, compostas do inseticida Imidacloprid e outra por busca direta. Verificou-se que em 71,73% das moscas coletadas por busca direta apresentaram crescimento fúngico, enquanto as moscas capturadas usando iscas químicas apresentaram apenas 28,26% de crescimento fúngico. No teste realizado adicionando a isca química em meio de cultura BDA, não foi observado crescimento fúngico. Para estudos de fungos residentes em M. domestica, o uso do inseticida Imidacloprid como isca química não é recomendado, pois este produto pode inibir determinados microrganismos, inclusive possíveis biocontroladores de M. domestica.

Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence.

Research has shown that genetic polymorphisms in biotransformation enzymes, such as CYP1A1 and GSTM1, are related to a greater or lesser susceptibility to various cancers. We made an analysis of CYP1A1m1 SNP and GSTM1 null genotypes in a family group (71 members) related by consanguinity who had an unusually high incidence of cancer and a high frequency of smokers. There were no significant differences in genotype frequencies in this family when compared to data for Brazilian populations. Possibly, the high incidence of cancer in this sample is associated with smoking and/or other factors not detected in this survey.

Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling.

Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10(-5) M) and relaxed by electrical field stimulation (20 V, 1-32 Hz) in the presence or absence of PnTx2-6 (10(-8) M). Cavernosal strips from nNOS- and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10(-5) M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) and ω-conotoxin GVIA (10(-6) M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as ω-conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production.

The death-promoting molecule tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is not required for the development of peripheral lymphopenia or granuloma necrosis during infection with virulent Mycobacterium avium.

Disseminated infection with virulent Mycobacterium avium in C57Bl/6 (B6) mice leads to severe lymphocyte depletion in secondary lymphoid organs. In this study, we found an up-regulation of caspase-8 activity in spleen cell extracts from M. avium 25291-infected B6 mice compared to non-infected mice. The activation of this extrinsic apoptotic pathway correlated with an increase in inter-nucleosomal DNA fragmentation in CD4(+) spleen cells, as analysed by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. These data suggest the involvement of death receptors in the induction of lymphocyte loss in the spleen, but previous work has excluded a role for tumour necrosis factor (TNF) receptors and Fas/CD95 in M. avium-induced lymphopenia. TNF-related apoptosis-inducing ligand (TRAIL) is expressed by different cell types of the immune system and induces apoptosis and killing of tumour cells while sparing normal cells. Here we used TRAIL(-/-) mice to determine if the absence of TRAIL prevented M. avium-induced immune pathology. We found that TRAIL-deficient mice still developed splenic lymphopenia during disseminated infection or granuloma necrosis during low-dose infections while exhibiting slightly increased susceptibility to M. avium 25291 when compared to B6 mice. However, in vivo proliferation of less virulent strains of M. avium was not influenced by TRAIL deficiency despite a decrease in interferon-γ production in infected B6.TRAIL(-/-) mice compared to B6 mice. Our results show that TRAIL does not play a significant role in either M. avium-induced pathology or protective immunity.

Transfer of IgE-mediated hypersensitivity with autologous stem cell transplantation.

In this paper, the transfer of IgE-mediated food allergy by means of autologous stem cell transplantation in a 24-years old male patient is reported.

Isolamento e seleção de fungos para controle de larvas de terceiro instar de Musca domestica / Isolation and selection of fungi in order to control Musca domestica third-instar larvae

O controle biológico no Brasil vem crescendo devido aos problemas gerados pelo uso indiscriminado de inseticidas químicos. A Musca domestica representa o maior problema em granjas avícolas devido às condições favoráveis para seu crescimento populacional. Sendo assim, foram realizadas capturas de dípteros muscoides em um aviário na região de Montes Claros, MG, usando armadilhas contendo isca química e captura por busca direta e, destas moscas, foram isolados e identificados fungos residentes nestes insetos. Os fungos isolados foram duas espécies do gênero Aspergillus sp., um do gênero Memnoniella sp., Scopulariopsis sp., Paecilomyces sp e um fungo da família Moniliaceae. Foram também requeridos junto ao CENARGEM/EMBRAPA as espécies de fungos entomopatogênicos Beauveria bassiana CG 470 e CG 472; Metarhizium anisopliae CG 34 e CG 312 e o Paecilomyces sp. CG 301. As espécies selecionadas para os bioensaios foram um Aspergillus sp., Memnoniella sp. e os Metarhizium anisopliae CG 34 e CG 312 por terem boa esporulação. Os fungos Aspergillus sp. e o Memnoniella sp. não apresentaram capacidade entomopatogênica, os fungos M. anisopliae CG 34 e CG 312 foram bastante eficientes em controlar a emergência dos adultos de M. domestica, mostrando-se bons agentes de controle biológico.

Use of biological control measures in Brazil has been increasing because of the problems generated from the indiscriminate use of chemical insecticides. Musca domestica represents the biggest problem to poultry farms due to the favorable conditions for its population growth. The present study was therefore conducted, beginning with captures of muscoid diptera on a poultry farm in the Montes Claros region, state of Minas Gerais, Brazil, using traps containing chemical bait and as well as capture by direct search, and the fungi resident on these flies was isolated and identified. The isolated fungi were two species of Aspergillus sp., one each from the genera Memnoniella sp., Scopulariopsis sp., Paecilomyces sp., and one fungi of the family Moniliaceae. Also, the entomopathogenic species of fungi Beauveria bassiana CG 470 and CG 472, Metarhizium anisopliae CG 34 and CG 312, and Paecilomyces sp. CG 301 were requested from CENARGEM/EMBRAPA. The species selected for the bioassays were Aspergillus sp., Memnoniella sp. and Metarhizium anisopliae CG 34 and CG 312. The fungi Aspergillus sp. and the Memnoniella sp. did not present entomopathogenic capacity; the fungi Metarhizium anisopliae CG 34 and CG 312 were sufficiently efficient in controlling the emergence of the adults of Musca domestica, showing themselves good agents of biological control.