Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture

Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent either sham operation or CLP. Rats subjected to CLP were treated by intraperitoneal injection with ""basic support"" and CBD (at 2.5, 5, or 10 mg/kg once or daily for 9 days after CLP) or vehicle. Six hours after CLP (early times), the rats were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus, striatum, and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day (late times), the rats were submitted to the inhibitory avoidance task. After the test, the animals were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus) were obtained and assayed for TBARS formation and protein carbonyls. The acute and extended administration of CBD at different doses reduced TBARS and carbonyl levels in some organs and had no effects in others, ameliorated cognitive impairment, and significantly reduced mortality in rats submitted to CLP. Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality. (C) 2010 Elsevier B.V. All rights reserved.

Histological effects of intratympanic gentamicin on the vestibular organ of guinea pigs

Background: Transtympanic administration of gentamicin may be suitable to achieve unilateral vestibular ablation, in order to control unilateral Meniere`s disease. In low doses, gentamicin appears to affect selectively the vestibular system, with relative sparing of the cochlea. An experimental study on guinea pigs was conducted to determine what single dose of gentamicin would produce a unilateral vestibular organ lesion when applied to the middle ear. Study design: Experimental and prospective. Methods: Four groups of guinea pigs received different gentamicin doses ( 1, 5, 10 and 25 mg) administered to the middle ear. The animals` vestibular organs were then assessed by scanning electron microscopy, in order to quantify the level of vestibular damage. Results: Study of the utricular macula and the ampullar crista of the lateral semicircular canal revealed vestibular neuroepithelial lesions in all infused ears. Conclusions: The severity of the vestibular neuroepithelial lesions was dose-dependent. Lower gentamicin doses were observed to damage vestibular structures more than cochlear structures.

Vitamin E and tannic acid improve DNA damage in rats submitted chronic ethanol administration

Purpose - Chronic ethanol consumption induces lipid peroxidation by increasing free radicals or reducing antioxidants and may increase damage to hepatic DNA. Tannins are polyphenolic metabolites present in various plants and one of their effects is antioxidant activity that reduces lipoperoxidation, as is the case for vitamin E. This paper aims to assess the role of tannic acid and vitamin E in lipid peroxidation and in DNA damage in rats receiving ethanol. Design/methodology/approach - A total of 60 Wistar rats were divided into six groups: control + ethanol (0-24hs), tannic acid + ethanol (0-24 hs), and vitamin E + ethanol (0-24 hs). The animals were sacrificed immediately (0 hour) or 24 hours after a period of four weeks of ethanol administration and the following measurements were made: plasma vitamin E and liver glutathione, thiobarbituric acid resistant substances, and a-tocopherol. The comet test was also applied to hepatocytes. Findings - Ethanol administration led to an increase in DNA damage (148.67 +/- 15.45 versus 172.63 +/- 18.94) during a period of 24 hours which was not detected in the groups receiving tannic acid or vitamin E. Steatosis was lower in the groups receiving tannic acid. Originality/value - The paper highlights that antioxidant role of vitamin E and of tannic acid in biological systems submitted to oxidative stress should be reevaluated, especially regarding the protective role of tannic acid against hepatic steatosis.

Postembryonic Development of Rectal Pads in Bees (Hymenoptera, Apidae)

The morphology and development of the digestive tract of insects has been extensively studied, but little attention has been given to the development of the rectal pads. These organs are responsible for absorption of water and salts. In insects where they occur, there are usually six ovoid rectal pads located in the medial-anterior portion of the rectum. The rectal pad has three types of cells: principal, basal, and junctional. The arrangement of these three cell types delimits an intrapapillary lumen. The aim of the current study is to describe the development of the rectal pads during postembryonic development of Melipona quadrifasciata anthidioides and Melipona scutellaris. Specimens were analyzed at the following developmental stages: white-, pink-, brown-, and black-eyed pupae, and adult workers. The development of the rectal pad begins as a thickening of the epithelium in white-eyed pupae at 54 hr. At this stage, there is neither a basal cell layer nor intrapapillary lumen. The basal layers begin to form in the pink-eyed pupa and are completely formed at the end of the development of the brown-eyed pupa. In the brown-eyed pupal stage, the intrapapillary lumen is formed and the junctional cells are positioned and completely differentiated. Necrotic and apoptotic cell death were detected along with cell proliferation in the whole rectum during pupal development, suggesting that the development of the rectal pads involves cell proliferation, death, and differentiation. The rectal pads originate only from the ectoderm. Anat Rec, 292:1602-1611, 2009. (C) 2009 Wiley-Liss, Inc.

The genome of the blood fluke Schistosoma mansoni

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

NO EVIDENCE OF PATHOLOGICAL AUTOIMMUNITY FOLLOWING MYCOBACTERIUM LEPRAE HEAT-SHOCK PROTEIN 65-DNA VACCINATION IN MICE

Heat-shock proteins (HSPs) are currently one of the most promising targets for the development of immunotherapy against tumours and autoimmune disorders. This protein family has the capacity to activate or modulate the function of different immune system cells. They induce the activation of monocytes, macrophages and dendritic cells, and contribute to cross-priming, an important mechanism of presentation of exogenous antigen in the context of MHC class I molecules, These various immunological properties of HSP have encouraged their use in several clinical trials. Nevertheless, an important issue regarding these proteins is whether the high homology among HSPs across different species may trigger the breakdown of immune tolerance and induce autoimmune diseases. We have developed a DNA vaccine codifying the Mycobacterium leprae Hsp65 (DNAhsp65), which showed to be highly immunogenic and protective against experimental tuberculosis. Here, we address the question of whether DNAhsp65 immunization could induce pathological autoimmunity in mice. Our results show that DNAhsp65 vaccination induced antibodies that can recognize the human Hsp60 but did not induce harmful effects in 16 different organs analysed by histopathology up to 210 days after vaccination. We also showed that anti-DNA antibodies were not elicited after DNA vaccination. The results are important for the development of both HSP and DNA-based immunomodulatory agents.

Options for monitoring diabetic cats

The key to successful long-term management of diabetes in cats is individualization of advice to suit cat and owner. A relationship based on trust and cooperation between veterinarian and client leads invariably to the most satisfactory outcome. Success requires knowledge of the options for monitoring diabetic cats, selection and adaptation of appropriate techniques for each individual case, and provision of ongoing support and guidance for owners. The ongoing treatment of a diabetic cat can be one of the more rewarding experiences of feline practice, and many diabetic cats and their owners come to occupy a special place within the clinic environment. This chapter provides a comprehensive overview of the current options for monitoring diabetes in cats and guidelines for application of the techniques to clinical cases.

Chemokines expression during Leptospira interrogans serovar Copenhageni infection in resistant BALB/c and susceptible C3H/HeJ mice

The role of innate immune responses in protection against leptospirosis remains unclear. We examined the expression of the chemokines CCL2/JE (MCP-1), CCL3/MIP-1 alpha (MIP-1 alpha) and CXCL1/KC (IL-8) regarding resistance and susceptibility to leptospirosis in experimental mice models BALB/c and C3H/HeJ, respectively. A virulent strain of Leptospira interrogans serovar Copenhageni was used in this study. Twenty-five animals of each mouse strain of C3H/HeJ and BALB/c, were infected intraperitoneally with 106 cells. Five un-infected animals of each strain were kept as control. Mortality of C3H/HeJ mouse was observed while BALB/c mice were asymptomatic. The presence of leptospire DNA in tissues of infected animals was demonstrated by PCR. Chemokines were measured in serum, spleen, liver, kidney and lung of both strains of animals using immunoenzymatic assay (ELISA). Elevations in the levels of chemokines MCP-1 and IL-8 occurred in all organs and sera of C3H/HeJ and BALB/c infected mice. The levels of MIP-1 alpha were lower when compared to MCP-1 and IL-8 in all analyzed organs, with a slight increase in liver and kidney. Our results indicate that the expression of inflammatory mediators can vary greatly, depending on the tissue and mouse strains. It is possible that the resistance to Leptospira can be partially correlated to the increase of MIP-1 alpha observed in BALB/c mice, while an increasing and a sustained expression of MCP-1 and IL-8 in the lungs of C3H/HeJ mice can be correlated to the severity and progression of leptospirosis. (C) 2009 Elsevier Ltd. All rights reserved.

Transplacental transmission of Toxoplasma gondii in reinfected pregnant female canines

Twelve pregnant female canines, naturally infected with Toxoplasma gondii, were reinfected with T. gondii: three (GI) received tachyzoites subcutaneously (1.0 x 107), three (GII) were orally inoculated with oocysts (1.5 x 104), and six (GIII) were kept as a nonreinfected control group. All the reinfected female canines (GI and GII) miscarried or presented fetal death, while only one GIII female presented a stillborn in a litter of four pups (P < 0.01). Fever, lymphoadenopathy, miscarriage, and fetal death were the main clinical alterations observed. The highest serological titers detected through the indirect fluorescence antibody test (IFAT) were 1,024 (GI) and 4,096 (GII). In group III, the titers ranged between 64 and 256. By bioassays in mice, T. gondii was isolated in 17 organs of the reinfected adult canines, in 11 of the control group, and in 20 of the neonates. Positive immunostaining of cysts and/or tachyzoites were observed in 26 canine tissues (14 from GI and GII and ten from GIII). The agent was detected by immunohistochemistry in the encephalon of a neonate and in the spinal cord of a stillborn, thus, confirming that T. gondii infected canine fetuses, provoking miscarriages, even in bitches that presented primoinfection.