Estudo da freqüência de infecções por enteroparasitos e agentes quimioterápicos usados em pacientes pediátricos em uma comunidade de Porto Alegre, RS, Brasil

Parasitic infections caused by intestinal protozoan and helminths affect more than two billion people worldwide and chemotherapy is the most commonly used therapeutic procedure. Considering the problems created by parasitic infections and the incorrect use of drugs, the aim of this work was to detect the frequency of enteroparasites infection and to estimate the use of chemotherapeutic agents in children living in the periphery of the city of Porto Alegre, RS, Brazil. Ninety-six preschool age children, who had parasitological exams and who used antiparasitic drugs, were analyzed. The efficacy of treatment was evaluated by stool examination repeated six months after treatment. The same diagnostic test was used to evaluate parasitological cure, which was defined as absence of eggs and cysts in the stool. From these children, 79 (82.3%) were contaminated by some species of parasite, the most prevalent were Ascaris lumbricoides, Trichuris trichiura and Giardia lamblia. The most commonly used drugs were mebendazole (86% of prescriptions) and metronidazole (30.3%). The cure rate in the 79 children, examined 6 months after treatment, was 65.3% for A. lumbricoides and 66.1% for T. trichiura. This study suggests that a continuous education program regarding the prevention and treatment of parasitic infections is an essential tool for their eradication.As parasitoses provocadas por protozoários ou helmintos patogênicos afetam mais de dois bilhões de pessoas no mundo. Considerando os problemas gerados por infecções parasitárias e a necessidade do uso correto dos medicamentos prescritos, o objetivo deste trabalho foi detectar a freqüência de infecção por enteroparasitos e o uso de agentes quimioterápicos em crianças moradoras na periferia de Porto Alegre, RS, Brasil. Foram analisadas noventa e seis crianças em idade pré-escolar, que realizaram o exame parasitológico de fezes e que fizeram uso de antiparasitários. A eficácia do tratamento foi avaliada pelo exame parasitológico repetido seis meses após o tratamento. O mesmo teste diagnóstico foi utilizado para avaliar a cura que foi definida como a ausência de ovos e cistos nas fezes. Das crianças estudadas, 79 (82,3%) estavam infectadas com um ou mais parasitas, os mais prevalentes foram Ascaris lumbricoides, Trichuris trichiura e Giardia lamblia. Os antiparasitários mais utilizados foram mebendazol (86% das prescrições) e metronidazol (30,3%) de acordo com a prevalência da infecção. A porcentagem de cura das 79 crianças estudadas após 6 meses do tratamento foi 65,3% para A. lumbricoides e 66,1% para T. trichiura. Este estudo sugere que um programa de educação continuada voltado para a prevenção e tratamento das infecções parasitárias tem se mostrado uma ferramenta útil na erradicação destas patologias

Purinergic Cooperation Between P2Y2 and P2X7 Receptors Promote Cutaneous Leishmaniasis Control: Involvement of Pannexin-1 and Leukotrienes

The release of damage-associated molecular patterns, including uridine triphosphate (UTP) and adenosine triphosphate (ATP) to the extracellular milieu is a key component of innate immune response to infection. Previously, we showed that macrophage infection by the protozoan parasite Leishmania amazonensis—the etiological agent of cutaneous leishmaniasis—can be controlled by ATP- and UTP-mediated activation of P2Y and P2X7 receptors (activated by UTP/ATP and ATP, respectively), which provided comparable immune responses against the parasite. Interestingly, in context of Leishmania amazonensis infection, UTP/P2Y triggered apoptosis, reactive oxygen species, and oxide nitric (NO) production, which are characteristic of P2X7 receptor activation. Here, we examined a possible “cross-talk” between P2Y2 and P2X7 receptors, and the requirement for pannexin-1 (PANX-1) in the control of L. amazonensis infection in mouse peritoneal macrophages and in vivo. UTP treatment reduced L. amazonensis parasite load, induced extracellular ATP release [which was pannexin-1 (PANX-1) dependent], and triggered leukotriene B4 (LTB4) production in macrophages. UTP-induced parasite control was blocked by pharmacological antagonism of P2Y2 or P2X7 receptors and was absent in macrophages lacking P2X7 or PANX-1. In addition, ATP release induced by UTP was also inhibited by PANX-1 blocker carbenoxolone, and partially reversed by inhibitors of vesicle traffic and actin cytoskeleton dynamics. In vivo, UTP treatment reduced footpad and popliteal lymph node parasite load, and the lesion in wild-type (WT) mice; fact not observed in P2X7−/− mice. Our data reveal that P2Y2 and P2X7 receptors cooperate to trigger potent innate immune responses against L. amazonensis infection

In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model

BACKGROUND: ATP is an important signalling molecule in the peripheral and central nervous system. Both glioma growth and tumor resection induces cell death, thus liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed very slowly by gliomas when compared with astrocytes and induce neuronal cell death and glioma proliferation. The objective of the present study was to test the involvement of extracellular ATP in glioblastoma growth in a rat glioma model. METHODS: To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS. One million glioma C6 cells in 3 microliters of DMEM/FCS were injected in the right striata of male Wistar rats, 250–270 g. After 20 days, the rats were decapitated and the brain sectioning and stained with hematoxylin and eosine. We performed immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with primers for the NTPDase family. RESULTS: C6 glioma cells effectively have a low expression of all NTPDases investigated, in comparison with normal astrocytes. The implanted glioma co-injected with apyrase had a significant reduction in the tumor size (p < 0.05) when compared with the rats injected only with gliomas or with gliomas plus inactivated apyrase. According to the pathological analysis, the malignant gliomas induced by C6 injection and co-injected with apyrase presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. Reduction of proliferation induced by apyrase co-injection was confirmed by counting the percentage of Ki67 positive glioma cell nuclei. According to counts with CD31, vessel density and neoformation was higher in the C6 group 20 days after implantation. Confirming this observation, rats treated with apyrase presented less VEGF staining in comparison to the control group. CONCLUSION: These results indicate that the participation of extracellular ATP and the ecto-nucleotidases may be associated with the development of this type of brain tumor in an in vivo glioma model

Uso de omeprazol en el hospital universitario de Porto Alegre-RS (Brasil)

Las hemorragias intestinales son causa importante de internamiento hospitalario y muerte, siendo significativamente relevante en pacientes críticamente debilitados y con artritis reumatoide y osteoartritis que usan antiinflamatorios no esteroídicos (AINE). El omeprazol es el medicamento de elección para profilaxis de úlcera de estrés, prevención de complicaciones relativas a los AINE, ya que previene tanto de la úlcera duodenal como gástrica y la erradicación del H pylori junto con antibióticos. El objetivo de este estudio fue determinar la frecuencia, indicaciones de uso y características de la población usuaria de omeprazol. Se realizó un estudio de utilización de medicamentos cualitativo y cuantitativo. La población estuvo constituida por adultos internados en un Hospital Universitario. De los 91 pacientes estudiados, la mayoría (24,2%) tenía cáncer. El tiempo medio de internamiento y uso del omeprazol fue de 20 y 12 días respectivamente. El equipo de cirugía abdominal fue el que más prescribió el medicamento, y la principal indicación de uso fue en el post-operatorio quirúrgico. Aunque la mayoría de las indicaciones para el uso del omeprazol haya sido aceptable, estas podrían estar mejor evaluadas. Sería recomendable la implantación de un programa de atención farmacéutica y la creación de un protocolo de utilización de omeprazol con el fin de prescribir el medicamento de forma racional y adecuada para cada paciente

Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice.

This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50 µl/paw) or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks), and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20 mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and anti-inflammatory agents bupropion and celecoxib might represent an attractive therapeutic strategy for depression

Determination of IL-1β, and BDNF levels in the brain of CFA-treated mice: effects of treatment with bupropion and celecoxib.

<p>Effect of intraplantar injection of CFA (50 μl/paw) at 2 weeks: IL-1β levels in the (A) whole brain, (B) cortex and (C) hippocampus. Effect of treatment with celecoxib and bupropion both at (30 mg/kg, p.o, once a day, 7 days) and combined effect of bupropion plus celecoxib (3 mg/kg, p.o, once a day, 7 days). (D) BDNF levels in cortex. Effects of treatment with celecoxib and bupropion (both at 30 mg/kg, p.o, once a day, 7 days) and combination of bupropion and celecoxib (both at 3 mg/kg, p.o, once a day, 7 days). Each column represents the mean ± SEM of <i>4</i> animals per group. **P < 0.01 significantly different from Saline+Saline group, ^# P < 0.05 and ^{# #} P < 0.01 significantly different from CFA+Saline group (ANOVA followed by Bonferroni’s post-hoc test).</p

Assessment of pregabalin and dipyrone effects on the mechanical allodynia, paw edema and depressive-like behaviour induced by CFA.

<p>Effect of intraplantar injection of CFA (50 μl/paw) at 2 weeks. (A) Mechanical paw withdraw threshold analyzed by using the von Frey test; (B) Paw edema analyzed in a plesthysmometer (difference between the right and the left paws); and (C) immobility time in the tail suspension test (TST). Effects of treatment with dipyrone (30 and 300 mg/kg, p.o., once a day, during 7 days) or pregabalin (30 mg/kg, p.o., once a day, for 7 days). Each column represents the mean ± SEM of 6 to 8 animals per group. *P < 0.05 and **P < 0.01 significantly different from saline + saline group, and ^# P < 0.05 and ^{# #} P < 0.01 significantly different from CFA + saline group (ANOVA followed by Bonferroni’s post-hoc test).</p

Immunolabelling for COX-2 in the cortex brain of CFA-treated mice: effects of treatment with bupropion and celecoxib.

<p>Immunohistochemistry analysis for COX-2 after intraplantar injection of CFA (50 μl/paw) at 2 weeks. Arrowheads (▲) indicate positive immunostaining for COX-2. Representative images of immunohistochemistry analysis for COX-2 in the mouse brain cortex: (A) schematic representation of the mouse brain indicating the region used for quantification (C) Control saline + saline group, (D) CFA + saline, (E) CFA + celecoxib (30 mg/kg, p.o., once a day, 7 days; respectively), (F) CFA + bupropion (30 mg/kg, p.o., once a day, 7 days; respectively), (G) CFA + bupropion and celecoxib (3 mg/kg, p.o., once a day, 7 days; both drugs). (B) Graphic showing the semi-quantitative analysis of immunostaining for COX-2. Scale bar represents 10,000 µm. Each column represents the mean ± SEM of <i>4</i> animals per group. **P < 0.01 significantly different from Saline+Saline group, ^# P < 0.05 significantly different from CFA+Saline group (ANOVA followed by Bonferroni’s post-hoc test).</p