Patents of drugs extracted from Brazilian medicinal plants

Background: Plants synthesise a vast repertoire of chemicals with various biological activities. Brazilian enormous botanical diversity facilitates the development of novel ethical drugs for the treatment of diseases in humans. Objective: To present therapeutic patent applications comprising Brazilian native plants published in the 2003 - 2008 period in light of legal aspects of patentability of biodiversity and public health concerns. Methods: Therapeutic patent applications related to Brazilian medicinal plants available at both the European Patent Office and the Brazilian National Institute of industrial Property databases were reviewed. Results/conclusion: Twenty-five patents are presented, most of which concern inflammatory, allergic, parasitic, infectious or digestive diseases, including extracts from Carapa guianensis, Copaifera genus, Cordia verbenacea, Erythrina mulungu, Physalis angulata and other pharmaceutical compositions with antileishmanial, antimalarial or trypanocidal activity. Brazilian research centres and universities are responsible for most of these inventions.

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

The aim of the present work was to compare colonic mucosa and plasmatic oxidative stress measured concomitantly and with different degrees of injury in rats with colitis induced by trinitrobenzene sulfonic acid. Three groups were studied: control group, colitis group, and colitis exacerbated by diclofenac. Enzymatic markers of colon injury showed enhanced activity in both groups with colitis. The colitis group treated with diclofenac presented higher colonic damage score than the other groups. In both groups with colitis, higher values of tert butyl hydroperoxide-initiated-chemiluminescence and thiobarbituric acid-reactive substances in tissue and decreased total radical-trapping antioxidant potential (TRAP) levels in plasma were found. In conclusion, independently of the degree of colonic mucosa injury and inflammation, oxidative stress in tissue occurs as a consequence of pro-oxidants increase, and is not explained by a reduction of antioxidant defenses. In both conditions, TRAP determination decreases in plasma, but not in tissue.

Myenteric Denervation Downregulates Galectin-1 and-3 Expression in Gastric Carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Profiles of gene polymorphisms in cytokines and toll-like receptors with higher risk for gastric cancer

Background: Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims: The purpose of this study was to investigate the combined effect of the pro- and anti-inflammatory cytokines and toll-like receptors polymorphisms on the chronic gastritis and gastric cancer risk in a Brazilian population sample. Methods: We evaluated 669 DNA samples (200 of gastric cancer [GC], 229 of chronic gastritis [CG], and 240 of healthy individuals [C]). Ten polymorphisms were genotyped: IL-1RN and TLR2 -196 to -174 del using the allele-specific PCR method and TNF-A (rs1800629; rs1799724), TNF-B (rs909253), IL-8 (rs4073; rs2227532), IL-10 (rs1800872) and TLR4 (rs4986790; rs4986791) using PCR-RFLP. Results: Polymorphisms TNF-A-308G/A, IL-8-251A/T, TNF-B + 252A/G and TLR4 + 1196C/T were not associated with risk of any gastric lesion. However, an association with increased risk for GC was observed for polymorphisms IL-1RNL/2 (p < 0.001), TNF-A-857C/T (p = 0.022), IL-8-845T/C (p < 0.001), IL-10-592C/A (p < 0.001), TLR2ins/del (p < 0.001), and TLR4 + 896A/G (p = 0.033). In CG, an association was observed only with polymorphisms IL-1RNL/2 and IL-10-592A/C (p < 0.001 for both). A combined analysis of these six polymorphisms associated with GC revealed a profile with two to four combined genotypes which confer a higher risk of gastric carcinogenesis, with an OR increased 2.95-fold to 50.4-fold, highlighting the combinations IL-1RN2/TNF-A-857T/IL-8-845C, IL-1RN2/IL-8-845C/TLR2del, IL-1RN2/IL-10-592A/TLR4 + 896G, IL-10-592A/TLR2del/ TLR4 + 896G, and IL-1RN2/TNFA-857T/IL8-845C/TLR2del. Conclusions: Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together. © 2012 Springer Science+Business Media New York.

Methylation pattern of THBS1, GATA-4, and HIC1 in pediatric and adult patients infected with helicobacter pylori

Background: Helicobacter pylori infection is usually acquired in childhood and persists into adulthood if untreated. The bacterium induces a chronic inflammatory response, which is associated with epigenetic alterations in oncogenes, tumor-suppressor genes, cell-cycle regulators, and cell-adhesion molecules. Aim: The aim of this study was to analyze the effect of H. pylori infection on the methylation status of Thrombospondin-1 (THBS1), Hypermethylated in cancer 1 (HIC1) and Gata binding protein-4 (GATA-4) in gastric biopsy samples from children and adults infected or uninfected with the bacterium and in samples obtained from gastric cancer patients. Methods: The methylation pattern was analyzed with methylation-specific PCR. Results: Our results showed that H. pylori infection was associated with methylation of the promoter regions of the THBS1 and GATA-4 genes in pediatric and adult samples (p < 0.01). HIC1 showed the lowest level of methylation, which was not an early event during gastric carcinogenesis. Conclusions: The results from this study indicate that methylation of THBS1 and GATA-4 occurs in the early stages of chronic gastritis and gastric cancer in association with H. pylori infection; however, in gastric cancer samples, other mechanisms cooperate with the down-regulation of these genes. Methylation of HIC1 may not be the principal mechanism implicated in its down-regulation in gastric cancer samples. © 2013 Springer Science+Business Media New York.

Influence of post-transplant immunosuppressive therapy on gastrointestinal transit using biomagnetic method: a pilot study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Challenges to the treatment and new perspectives for the eradication of helicobacter pylori

Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.

Morbidity among nursing personnel and its association with working conditions and work organization

Introduction: Work organization patterns and working conditions experienced by nursing personnel in the hospital settings may be associated to increased morbidity among these health workers. Aim: To estimate the prevalence and factors associated with self-reported diseases among nursing personnel at the emergency hospital in Rio Branco/ State of Acre, Brazil. Methods: A cross-sectional study was conducted involving 272 participants who answered a questionnaire including sociodemographic characteristics, working conditions, lifestyles, work ability, and a fatigue perception scale. The self-reported diseases in the 12 months prior to data collection were considered the dependent variable. Results: A total of 85.7% of the participants reported one or more diseases in the past 12 months. Most prevalent diseases were: musculoskeletal diseases (37.1%), digestive diseases (28.7%), mental disorders (28.3%), work injuries (27.9%), and respiratory diseases (26.8%). The following significant variables remained in the final model: high work demands (OR 2.69), reported fatigue (OR 3.59), night work (OR 6.55) and being a technician or nursing assistant (OR 4.23). Conclusions: Variables related to working conditions and work organization were associated with the occurrence of reported diseases among nursing professionals. Health promotion measures at work require a comprehensive approach including the working conditions and the work organization.

Incapacidade para o trabalho: análise dos benefícios auxílio-doença concedidos no estado de Rondônia

Trata-se de um estudo epidemiológico descritivo com objetivo de estimar a prevalência e a duração dos benefícios auxílio-doença, concedidos pelo Instituto Nacional de Seguro Social, bem como dos fatores associados à incapacidade para o trabalho entre os trabalhadores empregados em Rondônia em 2008. As prevalências foram apresentadas por 10.000 trabalhadores e estratificadas por sexo, idade, diagnóstico, atividade econômica, espécie e duração dos benefícios. Os homens apresentaram maiores prevalência e duração dos benefícios. Os benefícios previdenciários mostraramse 2,5 mais prevalentes do que os acidentários e ambos aumentaram com a idade. Os acidentários foram mais prevalentes na faixa etária de 50-59 anos. Silvicultura, construção civil e locação de mão de obra apresentaram as maiores prevalências. Os principais grupos diagnósticos foram lesões; doenças do sistema osteomuscular e doenças do aparelho digestivo. A duração dos benefícios auxílio-doença foi maior entre homens, com > 40 anos e na espécie previdenciária. A atividade econômica é um importante fator de risco para a incapacidade para o trabalho, e precisa ser mais bem explorada como tal visando melhorar a prevenção de doenças e diminuir o impacto na saúde dos trabalhadores decorrentes das condições ambientais e dos processos de trabalho.

Effects of ischemia and reperfusion on subpopulations of rat enteric neurons expressing the P2X7 receptor

BACKGROUND: Intestinal ischemia followed by reperfusion (I/R) may occur following intestinal obstruction. In rats, I/R in the small intestine leads to structural changes accompanied by neuronal death. AIM: To analyze the impact of I/R injury on different neuronal populations in the myenteric plexus of rat ileum. METHODS: The ileal artery was occluded for 35 min and animals were euthanized 6, 24, and 72 h, and 1 week later. Immunohistochemistry was performed with antibodies against the P2X7 receptor as well as nitric oxide synthase (NOS), calbindin, calretinin, choline acetyltransferase (ChAT), or the pan-neuronal marker anti-HuC/D. RESULTS: Double immunolabeling demonstrated that 100% of NOS-, calbindin-, calretinin-, and ChAT-immunoreactive neurons in all groups expressed the P2X7 receptor. Following I/R, neuronal density decreased by 22.6% in P2X7 receptor-immunoreactive neurons, and decreased by 46.7, 38, 39.8, 21.7, and 20% in NOS-, calbindin-, calretinin-, ChAT-, and HuC/D-immunoreactive neurons, respectively, at 6, 24, and 72 h and 1 week following injury compared to the control and sham groups. We also observed a 14% increase in the neuronal cell body profile area of the NOS-immunoreactive neurons at 6 and 24 h post-I/R and a 14% increase in ChAT-immunoreactive neurons at 1 week following I/R. However, the average size of the calretinin-immunoreactive neurons was reduced by 12% at 6 h post-I/R and increased by 8% at 24 h post-I/R. CONCLUSIONS: This work demonstrates that I/R is associated with a significant loss of different subpopulations of neurons in the myenteric plexus accompanied by morphological changes, all of which may underlie conditions related to intestinal motility disorder

Association Between Posttraumatic Stress Disorder Following Myocardial Infarction and Liver Enzyme Levels: A Prospective Study

Research in rodents demonstrated that psychological stress increases circulating levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress disorder and transaminases predicted coronary heart disease.

Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the isolated rat colon after morphine

The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M, intraluminally) and morphine (10(-4) M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrier.