Genotoxicity and cytotoxicity of antineoplastic drugs at environmentally relevant concentrations after long-term exposure.

Introduction: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations. Aims: Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model. Methods: Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL-1; 5-FU received 5-fluorouracil at 10ngL-1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL-1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained. Results: Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression. Conclusion: These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.

Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.

Electromyographic analysis of masseter and temporal muscles, bite force, masticatory efficiency in medicated individuals with schizophrenia and mood disorders compared with healthy controls.

This study aimed to comparatively analyse the electromyographic activity of the masseter and temporal muscles at rest and during mandible postural clinical conditions (right and left laterality, protrusion and maximum voluntary contraction), right and left maximum molar bite forces and the masticatory efficiency of individuals with schizophrenia or mood disorders - all medicated (medicated groups) compared with control group (healthy volunteers) via electromyography. Individuals were distributed into three groups: Group I (Schizophrenia - 20 individuals), Group II (mood disorders - 20 individuals) and Group III (Control - 40 individuals). Basically, the results were only statistically significant for the clinical mandible conditions and bite force. The most unsatisfactory results were observed in the medicated groups in relation to the control group. The group with mood disorders obtained the most unsatisfactory results compared with the group with schizophrenia. It was suggested by these observations that the association of mood disorders and schizophrenia with medication has negatively affected the stomatognathic system in relation to controls when the electromyography and bite force were used for the analysis.

Glucose homoeostasis in rats exposed to acute intermittent hypoxia.

AIM: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. METHODS: Male adult rats were submitted to 10 episodes of hypoxia (6% O2 , for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. RESULTS: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the ß-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. CONCLUSIONS: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased ß-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization.

Análise das doenças de notificação compulsória no município de cupira- pe, durante o período de 2007 a 2011 / analysis of compulsory notification diseases in the municipality of cupira-pe, from 2007 to 2011

Os indicadores e medidas de saúde demonstram o nível de saúde da população, medem a frequência ou a probabilidade da ocorrência de novos casos de doença na população. Assim, este trabalho buscou analisar medidas de saúde do município de Cupira, Pernambuco, visando elaborar um prévio diagnóstico da situação saúde da população referente às doenças de notificação compulsória. As informações foram obtidas no Sistema de Informação de Agravos de Notificação (SINAN) do município de Cupira, nos anos de 2007 a 2011, no período de janeiro a dezembro. As enfermidades registradas como confirmadas no período de estudo foram: esquistossomose (38,9/10.000 hab.), dengue (33,3 casos/10.000 hab.), hanseníase (12,3 casos/10.000 hab.), tuberculose (9,4 casos/10.000 hab.), doença de chagas guda (2,56/10.000 hab.), leishmaniose tegumentar americana (1,28 casos/10.000 hab.), malária (1,6/10.000 hab.), meningite (0,85/10.000 hab.) e leishmaniose visceral (0,5 casos/10.000 hab.). Em relação &a

ANÁLISE DAS DOENÇAS DE NOTIFICAÇÃO COMPULSÓRIA NO MUNICÍPIO DE CUPIRA- PE, DURANTE O PERÍODO DE 2007 A 2011 / ANALYSIS OF COMPULSORY NOTIFICATION DISEASES IN THE MUNICIPALITY OF CUPIRA-PE, FROM 2007 TO 2011

Os indicadores e medidas de saúde demonstram o nível de saúde da população, medem a frequência ou a probabilidade da ocorrência de novos casos de doença na população. Assim, este trabalho buscou analisar medidas de saúde do município de Cupira, Pernambuco, visando elaborar um prévio diagnóstico da situação saúde da população referente às doenças de notificação compulsória. As informações foram obtidas no Sistema de Informação de Agravos de Notificação (SINAN) do município de Cupira, nos anos de 2007 a 2011, no período de janeiro a dezembro. As enfermidades registradas como confirmadas no período de estudo foram: esquistossomose (38,9/10.000 hab.), dengue (33,3 casos/10.000 hab.), hanseníase (12,3 casos/10.000 hab.), tuberculose (9,4 casos/10.000 hab.), doença de chagas guda (2,56/10.000 hab.), leishmaniose tegumentar americana (1,28 casos/10.000 hab.), malária (1,6/10.000 hab.), meningite (0,85/10.000 hab.) e leishmaniose visceral (0,5 casos/10.000 hab.). Em relação &a

The effect of dietary supplementation with 9-cis:12-trans and 10-trans:12-cis conjugated linoleic acid (CLA) for nine months on serum cholesterol, lymphocyte proliferation and polymorphonuclear cells function in Beagle dogs.

Conjugated linoleic acids (CLA), 9-cis:11-trans and 10-trans:12-cis, have been shown to be able to modify some immune cells parameters and plasma lipids in a variety of experiment models. Since lymphocytes and polymorphonuclear cells (PMNC) have a large spectrum functions in the immune response, the knowledge in this field has to be expanded. Beagle dogs were fed a control diet or a CLA supplemented diet for nine months. Blood was collected for biochemical analysis and lymphocyte and PMNC isolation. PMNC were assayed for lysosome content, phagocytic activity and superoxide anion production. A lymphocyte proliferation capacity assay was done. The CLA fed dogs had a 34% reduction in total cholesterol (P < 0.05), 28% in LDL (P < 0.05) and 28% non-HDL-cholesterol (P < 0.05). Neither of the PMNC parameters evaluated demonstrated significant alteration. Lymphocytes from CLA group increased by 45% their mitotic capacity (P < 0.05). Our study demonstrates that CLA can successfully modify the lipid profile of dogs (monogastrics) when fed at reasonable levels, but did not significantly alter inflammatory function as would generally predicted. Further, we had some indication that CLA modulated T cell responsiveness.