Preliminary findings from a new animal model for Peyronie`s disease involving extracorporeal shock waves

To develop an experimental model in rabbits to analyse the efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie`s disease. We used 15 adult male rabbits divided into three equal groups. In group 1 (no penile ESWT) rabbits had three sessions of ESWT with 2000 shocks each (15 kV), but a rubber mat was placed between the shock head and rabbit to protect the penis; the rabbits were killed at 7 days after the last session of ESWT. In group 2 the rabbits had three sessions of ESWT using the same parameters, and were killed immediately after the last session to analyse the penis. In group 3 the rabbits had three sessions of ESWT as before but were killed at 7 days after the last session, and the penile tissue analysed macroscopically and histologically. The results showed clearly that the model was efficient, creating a similar situation to that when applying ESWT in the human penis. All of the rabbits in groups 2 and 3 had haematomas and diffuse petechiae after ESWT, and only four had urethral and penile bleeding. Almost all macroscopic changes disappeared after 48 h and only one rabbit in group 3 after 7 days had a haematoma on the dorsal penile surface. The histology (assessed using haematoxylin and eosin staining) of the cavernous body of the penis showed: unchanged histology in group 1; in group 2 there was a dilated and congested vascular space in the cavernous body, with interstitial extensive bleeding in the dermis; and in group 3 there was an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibres and thickening of the tunica albuginea. The present model was efficient in producing tissue injury in the normal penis when treated with ESWT, suggesting that this promising model should be considered for use future studies of Peyronie`s disease.

Targeted Mutagenesis in Pathogenic Leptospira Species: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.

Neoskin development in the fetus with the use of a three-layer graft: an animal model for in utero closure of large skin defects

Objective: To assess the ability of a three-layer graft in the closuse of large fetal skin defects. Methods: Ovine fetuses underwent a large (4 x 3 cm) full-thickness skin defect over the lumbar region at 105 days` gestation (term = 140 days). A bilaminar artificial skin was placed over a cellulose interface to cover the defect (3-layer graft). The skin was partially reapproximated with a continuous nylon suture. Pregnancy was allowed to continue and the surgical site was submitted to histopathological analysis at different post-operative intervals. Results: Seven fetuses underwent surgery. One maternal/fetal death occurred, and the remaining 6 fetuses were analyzed. Artificial skin adherence to the wound edges was observed in cases that remained in utero for at least 15 days. Neoskin was present beneath the silicone layer of the bilaminar artificial skin. Conclusions: Our study shows that neoskin can develop in the fetus using a 3-layer graft, including epidermal growth beneath the silicone layer of the bilaminar skin graft. These findings suggest that the fetus is able to reepithelialise even large skin defects. Further experience is necessary to assess the quality of this repair.

Anti-aversive effects of the atypical antipsychotic, aripiprazole, in animal models of anxiety

Aripiprazole is a unique antipsychotic that seems to act as a partial agonist at dopamine D2-receptors, contrasting with other drugs in this class, which are silent antagonists. Aripiprazole may also bind to serotonin receptors. Both neurotransmitters may play major roles in aversion-, anxiety-and panic-related behaviours. Thus, the present work tested the hypothesis that this antipsychotic could also have anti-aversive properties. Male Wistar rats received injections of aripiprazole (0.1-10 mg/kg) and were tested in the open field, in the elevated plus and T mazes (EPM and ETM, respectively) and in a contextual fear conditioning paradigm. Aripiprazole (1mg/kg) increased the percentage of entries onto the open arms of the EPM and attenuated escape responses in the ETM. In the latter model, the dose of 0.1 mg/kg also decreased the latency to leave the enclosed arm, suggesting anxiolytic- and panicolytic-like properties. This dose also decreased the time spent in freezing in a contextual fear conditioning. No significant motor effects were observed at these doses. The present data support the hypothesis that aripiprazole could inhibit anxiety-related responses. Acting as a partial agonist at dopamine receptors, this drug could effectively treat schizophrenia and, in contrast with most antipsychotic drugs, alleviate aversive states.

Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression

The effects of microinjection of the nitric oxide (NO) precursor L-arginine (L-Arg), the NO synthase (NOS) inhibitors N-methyl-L-arginine (L-NAME) and 7-nitroindazole (7-NI), and the cyclic guanosine 3`,5`-monophosphate (cGMP) analog 8-Br-cGMP into the dorsal raphe nucleus (DRN) were assessed in rats using the elevated plus maze (EPM) and the forced swim test (FST). L-Arg (100 and 200 nmol) produced an anxiolytic-like effect in the EPM. 8-Br-cGMP (25 and 50 nmol) dose-dependently increased locomotor activity. In the FST, antidepressant-like effects were produced by L-Arg (50 and 100 nmol) and 8-Br-cGMP (12.5 and 25 nmol). Dual effects were observed with NOS inhibitors L-NAME and 7-NI in both the EPM and FST. While low doses of L-NAME (25 nmol) or 7-NI (1 nmol) induced a selective increase in EPM open arm exploration and a decrease in immobility time in the FST, high doses (L-NAME 400 nmol, 7-NI 10 nmol) decreased locomotor activity. These results show that interference with NO-mediated neurotransmission in the DRN induced significant and complex motor and emotional effects. Further studies are needed to elucidate the mechanisms involved in these effects. (C) 2007 Elsevier Inc. All rights reserved.

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by D-amphetamine (D-AMPH). In the first model (reversal treatment), rats received saline or D-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or D-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the D-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against D-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against D-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Neurobiology of panic disorder: From animal models to brain neuroimaging

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG). Stressing the difference between these emotions, neuroendocrinological results indicate that the hypothalamic-pituitary-adrenal axis is activated by anticipatory anxiety, but not by panic attack nor by electrical stimulation of the rat PAG. Functional neuroimaging has shown activation of the insula and upper brain stem (including PAG), as well as deactivation of the anterior cingulated cortex (ACC) during experimental panic attacks. Voxel-based morphometric analysis of brain magnetic resonance images has shown a grey matter volume increase in the insula and upper brain stem, and a decrease in the ACC of panic patients at rest, as compared to healthy controls. The insula and the ACC detect interoceptive stimuli, which are overestimated by panic patients. It is suggested that these brain areas and the PAG are involved in the pathophysiology of panic disorder. (C) 2008 Elsevier Ltd. All rights reserved.

Ultrastructural aspects of lingual papillae in squirrel monkey (Saimiri sciureus)

Saimiri sciureus is one of the smallest Cebidae native of Amazon region and also found at the biological reserve of northeast Atlantic forest. It is an omnivore animal, with diversified diet that directly influences the lingual mucosa, which includes certain types of papillae with different organization levels. The present study attempted to describe the morphological and ultrastructure aspects of the dorsal surface of the S. sciureus. Five tongues of de S. sciureus were analyzed from three males and two females who died from natural causes and were obtained from breeding colonies of CENP-Ananindeua-PA. Main macroscopic features were a general triangular shape with a craniocaudal elongation pointed apex. Tissue samples-apex, body, and root of tongue-were fixed in modified Karnovsky solution, following standard scanning protocol, mounted in stubs, coated by gold, and analyzed by Scanning Electron Macroscopy (SEM). Four types of papillae were described: filiform (along all tissue extension with 154 mu m of diameter), fungiform (along all tissue extension with 272 mu m of diameter), vallate [just three units in caudal (dorsal) portion with 830 mu m of diameter] and foliate (one pair at caudolateral surface with similar to 13 projections and 3000 mu m in length). Data analysis indicates that the distribution and ultra structural morphology of the S. sciureus lingual papillae are some similar to other primates. Microsc. Res. Tech. 74:484-487, 2011. (C) 2010 Wiley-Liss, Inc.

Light and scanning electron microcopy study of the tongue in Rhea americana

Morphological characteristics of the tongue were studied in adult rhea (Rhea americana). The lingual surface and the surface of epithelium-connective tissue interface of rhea tongue were examined macroscopically and by light and scanning electron microscopy. The rhea tongue revealed a triangular aspect, without adjustment of the inferior bill formation, occupying approximately of the length of the oral cavity. Lingual papilla-like structures were not observed over the lingual surface. The tongue mucosa was composed of a thick non-keratinized stratified squamous epithelium in the dorsal and ventral part, supported by a connective tissue core. The submucosa contained numerous glands with cytoplasmic granules, and luminal secretion was positive for histochemical reaction to Alcian Blue in pH 2.5 and PAS, and negative to Alcian Blue in pH 0.5. Despite the rudimentary characteristic of the tongue in rhea, our results suggest an important role of tongue secretions in food lubrication and humidification during the swallowing process, based on the enormous quantity of lingual glands in the submucosa and the histochemical characteristics of their secretions.

Could sudden death syndrome (SDS) in chickens (Gallus gallus) be a valid animal model for sudden unexpected death in epilepsy (SUDEP)?

Epilepsy is the most common serious neurological disorder and approximately 1% of the population worldwide has epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning fisk factors for SUDEP is conflicting, but potential risk factors include: young age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Similarly, sudden death syndrome (SDS) is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings and incidence of SDS these animals has recently increased worldwide. Moreover, the exactly cause of SDS in Gallus gallus is unknown, but is very probable that cardiac abnormalities play a potential role. Due the similarities between SUDEP and SDS and as Gallus gallus behavioral manifestation during SDS phenomenon is close of a tonic-clonic seizure, in this paper we suggest that epilepsy could be a new possible causal factor for SDS. (C) 2009 Elsevier Ltd. All rights reserved.

Ecological aspects of the free-living ticks (Acari: Ixodidae) on animal trails within Atlantic rainforest in south-eastern Brazil

In a recent ecological study of the ticks on animal trails within an area of Atlantic rainforest in south-eastern Brazil, Amblyomma aureolatum, A. brasiliense, A. incisum, A. ovale and Haemaphysalis juxtakochi were found questing on the vegetation. Most of the ticks recorded by a small, man-made dam on the forest border were A. dubitatum but a few A. brasiliense and A. cajennense, one A. incisum and one H. juxtakochi were also found. The seasonal activity of the ticks indicated that A. incisum and A. brasiliense had one generation/year. On the animal trails, most tick species and stages quested on the vegetation at a height of 30-40 cm above ground level. The questing larvae and adults of A. incisum tended to be found higher, however, with the greatest numbers recorded 40-50 cm (larvae) or 60-70 cm (adults) above ground level. Most of the adult ticks (81.1% -100%), nymphs (78.6%-100%) and larval clusters (100%) found on a forest trail remained questing at the same location over a 24-h period. Carbon-dioxide traps in the rainforest attracted, 50% of the ticks observed questing on the nearby vegetation and, curiously, the CO(2) traps set deep in the forest attracted far fewer ticks than similar traps set by the dam. The ecological relationships between the ticks, their hosts and the rainforest environment are discussed.