Sara Santos Bernardes

Profile of suicide attempts using intentional overdose with medicines, treated by a poison control center in Paraná State, Brazil

This study presents the profile of suicide attempts using intentional overdose with medicines, treated at the Poison Control Center in Londrina, Paraná State, Brazil. A retrospective study of cases treated from 1997 to 2007 was performed. Suicide attempts were significant among unemployed men, housewives, and retired women, and there was an association with other substances in 51.5% of the cases, with a higher frequency among men. 51.1% of the men combined the medicine with an alcoholic beverage, while in women, 84.8% of the associations involved other medicines. The most frequent pharmacological groups were tranquilizers (25.5%), antidepressants (17%), anticonvulsants (15%), and NSAIDs (11.9%). Prescribers must evaluate patients correctly before prescribing psychoactive drugs, since this is the pharmacological group most frequently associated with suicide attempts. Awareness-raising campaigns for rational use of medicines and social programs for suicidal patients should also help decrease the frequency of such cases.Este trabalho apresenta o perfil das tentativas de suicidio atendidas pelo Centro de Controle de Intoxicacoes da cidade de Londrina, Parana, Brasil. Foi realizado um estudo retrospectivo dos casos atendidos entre 1997-2007. As tentativas de suicidio foram significativas entre homens desempregados e mulheres donas-de-casa/aposentadas, e houve associacao com outras substâncias em 51,5% dos casos, sendo a frequencia maior entre os homens. 51,1% dos homens associaram o medicamento com bebida alcoolica, e entre as mulheres, 84,8% das associacoes se referiram a medicamentos. Os grupos farmacologicos de maior frequencia foram os tranquilizantes (25,5%), antidepressivos (17%), anticonvulsivos (15%) e AINES (11,9%), respectivamente. Os prescritores devem avaliar corretamente o paciente antes de receitar psicofarmacos, uma vez que esse e o grupo farmacologico mais frequente nas tentativas de suicidio. Campanhas de conscientizacao para o uso racional de medicamentos, juntamente com programas sociais de atendimento ao paciente suicida, tambem poderiam contribuir na diminuicao da frequencia desses casos.

Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

BackgroundPeripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner.MethodsWe evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain.ResultsThe severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = −0.95), TBARS (r = −0.98), carbonyl proteins (r = −0.99), and chymotrypsin-like proteolytic activity (r = −0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91).ConclusionsTaken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

Systemic oxidative profile after tumor removal and the tumor microenvironment in melanoma patients.

This study highlights the systemic oxidative changes in patients submitted to primary cutaneous melanoma removal. Cutaneous melanoma is highly aggressive and its incidence is increasing worldwide. We evaluated systemic oxidative stress (OS) and 3-nitrotyrosine (3-NT) expression in melanoma tissue in relation to the Breslow thickness in patients under surveillance. Forty-three patients with cutaneous melanoma and 50 healthy volunteers were recruited. Patients were divided into two groups according to the tumors Breslow thickness: T1/T2 (<2 mm) and T3/T4 (≥2 mm). Systemic OS and inflammatory mediators were evaluated in plasma, and the 3-NT expression was analyzed via immunohistochemistry. Compared with the controls, the patients had lower blood levels of reduced glutathione, higher malondialdehyde and thiol levels, and a higher total radical-trapping antioxidant parameter to uric acid ratio. The C-reactive protein and γ-glutamyl transpeptidase were increased only in the T3/T4 group. High levels of 3-NT were present only in T3/T4 patients. Our data suggested that a correlation exists between the Breslow thickness and a systemic pro-oxidant status, and that oxidative changes induced by the melanoma remain in the microenvironment post-surgery, demonstrating a role for oxygen species in melanoma.

Nimesulide-induced fatal acute liver failure in an elderly woman with metastatic biliary adenocarcinoma. A case report

CONTEXT Nimesulide is a selective inhibitor of the enzyme cyclooxygenase 2. Although considered to be a safe drug, cases of acute hepatitis and fulminant liver failure have been reported in Europe, the United States and South America, especially among elderly female patients. Until now, there had not been any reports in the literature relating to Brazilian subjects. CASE REPORT An 81-year old female who had been using nimesulide therapy for six days presented hematemesis and epistaxis two days before hospitalization. Clinical examination showed an extensive coagulation disorder, diffuse hematomas, hypotension and tachypnea. Laboratory tests revealed abnormalities in coagulation tests; leukocytosis; reduced platelet, hemoglobin and red blood cell counts; and elevated direct bilirubin, serum aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase and renal function biomarkers. Hepatitis B and C tests were not reactive. Carcinoembryonic antigen (CEA), CA-19-9 and CA-125 levels were increased by, respectively, 1,000, 10,000 and 13 fold, whereas the alpha-fetoprotein level was normal, thus indicating a malignant tumor in the bile duct that did not originate from the liver. Thirty-six hours after hospitalization, the patients condition worsened, leading to death. The necropsy findings included acute hepatitis with hepatocellular collapse, as well as metastasis of a carcinoma, probably from the bile duct. CONCLUSION Despite the carcinoma presented by the patient, nimesulide use may have contributed towards the fatal acute liver failure. Until this issue has been clarified, caution is required in prescribing nimesulide for liver disease patients.

Oxidative status and chymotrypsin-like activity in right and left ventricle hypertrophy in an experimental model of emphysema.

Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p<0.05). TAC also increased only in the E40 group. In the LV, chemiluminescence values increased from 4044.77±503.39 to 5517.10±388.27 in the E20 group and to 8169.14±1748.77URL/g tissue in the E40 group (p<0.05, both). TAC significantly increased in the E20 and E40 groups. No differences were detected in substances reactive to thiobarbituric acid or carbonyl proteins when comparing ventricles or doses. Chymotrypsin-like proteolytic activity significantly decreased in both groups and ventricles. Emphysema can induce right and left ventricle lipid peroxidation and result in antioxidant mobilization. These data together support the idea that cardiac hypertrophy in response to emphysema is mediated in part by proteolytic pathways with involvement of reactive species.

Isoflavin-β modifies muscle oxidative stress and prevents a thyrotoxicosis-induced loss of muscle mass in rats

We sought to verify whether isoflavin‐beta (Iso‐β), a mixture of isoflavones with antioxidant properties, could prevent thyrotoxicosis‐induced loss of muscle mass and the participation of oxidative stress (OS) in the mechanisms of this prevention.

Metformin: oxidative and proliferative parameters in-vitro and in-vivo models of murine melanoma

Cutaneous melanoma is one of the most lethal cancers because of its increased rate of metastasis and resistance to available therapeutic options. Early studies indicate that metformin has beneficial effects on some types of cancer, including melanoma. To clarify knowledge of the mechanism of action of metformin on this disease, two treatment-based approaches are presented using metformin on melanoma progression: an in-vitro and an in-vivo model. The in-vitro assay was performed for two experimental treatment periods (24 and 48 h) at different metformin concentrations. The results showed that metformin decreased cell viability, reduced proliferation, and apoptosis was a major event 48 h after treating B16F10 cells. Oxidative stress was characterized by the decrease in total thiol antioxidants immediately following 24 h of metformin treatment and showed an increase in lipid peroxidation. The in-vivo model was performed by injecting B16F10 cells into the subcutaneous of C57/BL6 mice. Treatment with metformin began on day 3 and on day 14, the mice were killed. Treatment of mice with metformin reduced tumor growth by 54% of its original volume compared with nontreatment. The decrease in systemic vascular endothelial growth factor, restoration of antioxidants glutathione and catalase, and normal levels of lipid peroxidation indicate an improved outcome for melanoma following metformin treatment, meeting a need for new strategies in the treatment of melanoma.

Antidepressants Self-Poisoning in Suicide and Suicide Attempt: Acute Toxicity and Treatment

It is estimated that a quarter of the patients that have been diagnosed with major depression attempt suicide during their lifetime, and 15% of these patients ultimately die from suicide. Antidepressants have been shown to be a highly effective treatment for depression; paradoxically, to achieve compliance, physicians must give patients access to a toxic drug, and a possible suicide method (Gunnell & Frankel, 1994; White, Litovitz & Clancy, 2008; Wong et al., 2010).