RESUMO

As far as we know, no report uses the Swenson transanal endorectal pull-through technique in an animal model. Our objective is to describe the use of this technique as an experimental model for training and research purposes. Ten Norfolk hybrid rabbits were randomly selected from our experimental laboratory, with a mean weight of 3539.3 (± 678.4) g. Neither colon preparation nor fast were used before the procedures. The surgical technique was based on the description performed by Levitt et al. (2013, J Pediatr Surg. 2013;48(11):2289-2295). Information related to the surgical procedures and the clinical evolution in the postoperative period were recorded and analyzed. There were no deaths or severe complications. The anesthetic and the surgical times were significantly higher for the first three animals of the experiment. Our animal model proved adequate to perform the transanal endorectal Swenson pull-through technique, allowing the training of surgical skills through a model similar to the human, with few anesthetic complications and good postoperative evolution, including postoperative follow-up. We believe that it will serve as a learning tool in many institutions that are continuously searching for improved new techniques and will support new researches in this area.

Assuntos

Modelos Animais , Reto , Animais , Coelhos , Reto/cirurgia , Canal Anal/cirurgia , Cirurgia Endoscópica Transanal/métodos , Humanos , Duração da Cirurgia

RESUMO

BACKGROUND: Celecoxib, an anti-inflammatory drug, combined therapies using antimicrobials and immune modulator drugs are being studied. OBJECTIVE: To assess whether Celecoxib has direct in vitro antifungal effect against the Paracoccidioides brasiliensis, the causative agent of Paracoccidioidomycosis-(PCM) and also if it improves the in vivo activity of neutrophils-(PMN) in an experimental murine subcutaneous-(air pouch) model of the disease. METHODS: The antifungal activity of Celecoxib(6 mg/mL) on P. brasiliensis-(Pb18) was evaluated using the microdilution technique. Splenocytes co-cultured with Pb18 and treated with Celecoxib(6 mg/mL) were co-cultured for 24, 48 and 72-hours. Swiss mice were inoculated with Pb18 and treated with Celecoxib(6 mg/kg) in the subcutaneous air pouch. Neutrophils were collected from the air pouch. Mitochondrial activity, reactive oxygen production, catalase, peroxidase, cytokines and chemokines, nitrogen species, total protein, microbicidal activity of PMNs and viable Pb18 cells numbers were analyzed. RESULTS: Celecoxib had no cytotoxic effect on splenocytes co-cultured with Pb18, but had a marked direct antifungal effect, inhibiting fungal growth both in vitro and in vivo. Celecoxib interaction with immune system cells in the air pouch, it leads to activation of PMNs, as confirmed by several parameters (mitochondrial activity, reactive oxygen species, peroxidase, KC and IL-6 increase, killing constant and phagocytosis). Celecoxib was able to reduce IL-4, IL-10 and IL-12 cytokine production. The number of recovered viable Pb18 decreased dramatically. CONCLUSIONS: This is the first report of the direct antifungal activity of Celecoxib against P. brasiliensis. The use of Celecoxib opens a new possibility for future treatment of PCM.

Assuntos

Antifúngicos , Celecoxib , Neutrófilos , Paracoccidioides , Paracoccidioidomicose , Animais , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/imunologia , Camundongos , Celecoxib/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/imunologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Citocinas/metabolismo , Células Cultivadas , Masculino , Baço/imunologia , Baço/citologia , Baço/efeitos dos fármacos , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo

RESUMO

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Assuntos

Doença de Alzheimer , Encéfalo , Modelos Animais de Doenças , Memória Espacial , Compostos de Vanádio , Animais , Masculino , Administração por Inalação , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Angiopatia Amiloide Cerebral/induzido quimicamente , Angiopatia Amiloide Cerebral/patologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/patologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/patologia , Placa Amiloide/induzido quimicamente , Placa Amiloide/patologia , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/toxicidade

RESUMO

The causative agent of tuberculosis in pinnipeds is Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including humans, can also be infected. The transmissibility of a pathogen is related to its virulence. The transmissibility of a M. pinnipedii strain (i.e., 1856) was investigated in a murine model and compared with that of two Mycobacterium bovis strains (i.e., 534 and 04-303) with different reported virulence. Non-inoculated mice (sentinels) were co-housed with intratracheally inoculated mice. Detailed inspection of mice to search for visible tuberculosis lesions in the lungs and spleen was performed, and bacillus viability at 30, 60, and 90 days post-inoculation (dpi) was assayed. A transmissibility of 100% was recorded at 30 dpi in sentinel mice co-housed with the inoculated mice from the M. pinnipedii and M. bovis 04-303 groups, as evidenced by the recovery of viable M. pinnipedii and M. bovis from the lungs of sentinel mice. Mice inoculated with M. pinnipedii (1856) and M. bovis (534) survived until euthanized, whereas five of the M. bovis 04-303-inoculated mice died at 17 dpi. This study constitutes the first report of the transmissibility of a M. pinnipedii strain in mice and confirms the utility of this experimental model to study virulence features such as the transmission of poorly characterized MTC species.

Assuntos

Caniformia , Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose , Humanos , Animais , Camundongos , Modelos Animais de Doenças , Tuberculose/patologia , Baço/patologia

RESUMO

Combined allergic rhinitis and asthma syndrome (CARAS) is an airway-type 2 immune response with a profuse inflammatory process widely affecting the world population. Due to the compromise of quality of life and the lack of specific pharmacotherapy, the search for new molecules becomes relevant. This study aimed to evaluate the effectiveness of the Morita-Bailys-Hillman adduct (CISACN) treatment in the CARAS experimental model. Female BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with CISACN. The treatment decreased the eosinophil migration to the nasal and lung cavities and tissues and the goblet cell hyperplasia/hypertrophy, attenuated airway hyperactivity by reducing the hyperplasia/hypertrophy of the smooth muscle and the extracellular matrix's thickness. Also, the treatment reduced the clinical signs of rhinitis as nasal rubbing and sneezing in a histamine-induced nasal hyperreactivity assay. The immunomodulatory effect of CISACN was by reducing OVA-specific IgE serum level, and IL-33, IL-4, IL-13, and TGF-ß production, dependent on IFN-γ increase. Furthermore, the effect of CISACN on lung granulocytes was by decreasing the p-p38MAPK/p65NF-κB signaling pathway. Indeed, CISACN reduced the p38MAPK and p65NF-κB activation. These data demonstrated the anti-inflammatory and immunomodulatory effects of the CISACN with scientific support to become a pharmacological tool to treat airway inflammatory diseases.

Assuntos

Acrilonitrila , Asma , Rinite Alérgica , Animais , Feminino , Camundongos , Acrilonitrila/administração & dosagem , Asma/tratamento farmacológico , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperplasia , Hipertrofia , Imunidade , Inflamação/tratamento farmacológico , Interleucina-4/farmacologia , Pulmão , Camundongos Endogâmicos BALB C , Ovalbumina , Qualidade de Vida , Rinite Alérgica/tratamento farmacológico , Células Th2

RESUMO

The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.

Assuntos

Córtex Suprarrenal , Humanos , Animais , Masculino , Gerbillinae/anatomia & histologia , Córtex Suprarrenal/metabolismo , Glândulas Suprarrenais/metabolismo , Corticosteroides/farmacologia , Hormônios/metabolismo , Envelhecimento , Esteroides/farmacologia

RESUMO

Campylobacter fetus spp. is a bacterium associated to reproductive losses in cattle worldwide. It is a venereal infectious disease known as bovine campilobacteriosis, with high impact mainly in countries with extensive production systems. Here, we show pathogenesis and diagnostic methods for Campylobacter fetus detection in cervico-vaginal mucus (CVM) samples from heifers experimentally infected and field cases from herds with low reproductive performance by campylobacteriosis infection. Bacterial culture, direct immunofluorescence test and qPCR were used as diagnostic methods to evaluate detection of C. fetus. In the experimental model 30 Aberdeen Angus and crossbred heifers and 4 Aberdeen Angus bulls for natural mating were assigned to 3 groups experimentally challenged with C. fetus subsp. fetus (Cff), C. fetus subsps venerealis (Cfv) and C. fetus subsp venerealis biovar intermedius (Cfvi), respectively, and a negative control group, all followed for 9 months. Also, field samples of CVM and aborted fetuses were recollected from seven beef cattle farms. Bacteriological culture had the higher C. fetus detection rate in CVM being the most appropriate, followed by qPCR (with commercial extraction DNA kit), direct immunofluorescence test and qPCR (with in-house extraction DNA method), in both, experimental model and field cases. From experimental model after natural mating, 62.5% and 25% heifers got pregnant from Cff and Cfvi groups, respectively, while from Cfv no pregnancy was detected. The strain more frequently detected was Cfvi, followed by Cff and Cfv. Colonization of Cff in female genital tract with high number of carriers and presence in aborted fetuses was evidenced, suggesting a high risk to bovine reproductive health. Bacteriemia was not detected after genital infection. Given the low detection rate of either test, we suggest the use of both, PCR based methods and bacterial culture could result in higher detection rate in farms with endemic campylobacteriosis.

Assuntos

Infecções por Campylobacter , Doenças dos Bovinos , Bovinos , Animais , Feminino , Masculino , Doenças dos Bovinos/epidemiologia , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/veterinária , Vagina/microbiologia , Colo do Útero , DNA

RESUMO

INTRODUCTION: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. METHODS: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. RESULTS: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. CONCLUSION: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.

Assuntos

Colite , Doença de Crohn , Oxigenoterapia Hiperbárica , Doenças Inflamatórias Intestinais , Humanos , Masculino , Camundongos , Animais , Antioxidantes/farmacologia , Doença de Crohn/terapia , Solução Salina/efeitos adversos , Estresse Oxidativo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Citocinas , Modelos Teóricos , Etanol/efeitos adversos

RESUMO

BACKGROUND: Ex vivo lung perfusion (EVLP) constitutes a tool with great research potential due to its advantages over in vivo and in vitro models. Despite its important contribution to lung reconditioning, this technique has the disadvantage of incurring high costs and can induce pulmonary endothelial injury through perfusion and ventilation. The pulmonary endothelium is made up of endothelial glycocalyx (EG), a coating of proteoglycans (PG) on the luminal surface. PGs are glycoproteins linked to terminal sialic acids (Sia) that can affect homeostasis with responses leading to edema formation. This study evaluated the effect of two ex vivo perfusion solutions on lung function and endothelial injury. METHODS: We divided ten landrace swine into two groups and subjected them to EVLP for 120 min: Group I (n = 5) was perfused with Steen® solution, and Group II (n = 5) was perfused with low-potassium dextran-albumin solution. Ventilatory mechanics, histology, gravimetry, and sialic acid concentrations were evaluated. RESULTS: Both groups showed changes in pulmonary vascular resistance and ventilatory mechanics (p < 0.05, Student's t-test). In addition, the lung injury severity score was better in Group I than in Group II (p < 0.05, Mann-Whitney U); and both groups exhibited a significant increase in Sia concentrations in the perfusate (p < 0.05 t-Student) and Sia immunohistochemical expression. CONCLUSIONS: Sia, as a product of EG disruption during EVLP, was found in all samples obtained in the system; however, the changes in its concentration showed no apparent correlation with lung function.

Assuntos

Lesão Pulmonar , Ácido N-Acetilneuramínico , Animais , Suínos , Respiração , Perfusão , Pulmão , Modelos Teóricos

RESUMO

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

RESUMO

INTRODUCTION: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.

RESUMO

Background and Aim: Infectious bovine keratoconjunctivitis is the most crucial ophthalmic disease among ruminants worldwide. Moraxella is the bacteria generally associated with this disease and leads to keratitis, conjunctivitis, corneal ulcers, or blindness. Platelet-rich plasma (PRP) effects in corneal ulcers and different ocular superficial diseases in animals and humans are beneficial and enhance rapid healing and improvement, but the effects in infectious keratoconjunctivitis in ruminants are uncertain. This study aimed to examine the effect of PRP on re-epithelization, corneal tissue, clinical signs, and matrix metalloproteinase (MMP) expression in sheep with infectious keratoconjunctivitis. Materials and Methods: Eighteen sheep were divided into three groups and subjected to a disease-induction experiment. Group 1 (G1) was administered 1.0 mL PRP subconjunctivally, Group 2 (G2) was administered 1.0 mL PRP subconjunctivally and 50 µL gentamicin drops, and the control group (CG) was administered 50 µL saline solution topically every 12 h. Clinical ophthalmologic examination, fluorescein staining, and photography were carried out. Ulcerated areas were measured employing J-Image software. Five and eleven days following the procedure, half of the animals from each group were euthanized, and their corneas were evaluated by histopathology and zymography. Results: Control Group and G2 epithelialized more rapidly. The CG exhibited fewer clinical signs of ocular disease. In histopathological analysis, in G2, alterations were observed only in the epithelium. The CG and G1 exhibited alterations in the epithelium, stroma, and Descemet's membrane. In zymography, a decline in MMP-2 expression in the animals treated with PRP was detected. Matrix metalloproteinase-9 was significantly expressed in the animals treated with PRP monotherapy, whereas PRP + gentamicin and CG caused a decrease. Conclusion: Platelet-rich plasma alone did not demonstrate any beneficial effect on re-epithelialization, a decline in clinical signs, tissue alterations, and expression of metalloproteinases. Platelet-rich plasma combined with gentamicin was capable of suppressing MMPs, primarily MMP-9, but do not display positive effects in re-epithelization, reduction of clinical signs, or tissue effects. These outcomes are similar to those discovered in untreated animals, so the use of PRP in patients with infectious keratoconjunctivitis does not offer greater benefits in sheep. Additional research is required to validate the results of PRP use in natural disease presentation.

RESUMO

Mancozeb is a fungicide commonly used in pest control programs, especially to protect vineyards. Its toxicity has already been evidenced in several studies. However, its influence on the composition and diversity of the gut microbiota remains unknown. In this work, the adverse impact of Mancozeb on the intestinal microbiota was investigated using a rodent model. Adult male Sprague Dawley rats were randomized into three groups: Control (standard diet), MZ1 (Mancozeb dose: 250 mg/kg bw/day), and MZ2 (Mancozeb dose: 500 mg/kg bw/day). After 12 weeks of experiment, animals were euthanized, and feces present in the intestine were collected. After fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ System. Alpha and beta diversity analysis showed significant differences between Control and Mancozeb groups (MZ1 e MZ2), but no difference between MZ1 and MZ2 was observed. Seven genera significantly increased in abundance following Mancozeb exposure, while five genera decreased. Co-occurrence analyses revealed that the topological properties of the microbial networks, which can be used to infer co-occurrence interaction patterns among microorganisms, were significantly lower in both groups exposed to Mancozeb when compared to Control. In addition, 23 differentially abundant microbial metabolic pathways were identified in Mancozeb-treated groups mainly related to a change in energy metabolism, LPS biosynthesis, and nucleotide biosynthesis. In conclusion, the exposure to Mancozeb presented side effects by changing the composition of the microbiota in rats, increasing bacterial diversity regardless of the dose used, reducing the interaction patterns of the microbial communities, and changing microbial metabolic pathways.

Assuntos

Fungicidas Industriais , Microbioma Gastrointestinal , Ratos , Masculino , Animais , Ratos Sprague-Dawley , RNA Ribossômico 16S/genética , Fezes/microbiologia

RESUMO

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.

Assuntos

Hipersensibilidade , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Hipersensibilidade/terapia , Alérgenos , Inflamação , Citocinas , Dessensibilização Imunológica , Imunoglobulina E

RESUMO

Sleep is essential for health: Adequate sleep is essential for healthy development and sleep deprivation results in several consequences. Indeed, sleep deprivation early in life is associated with poor behaviour and cognition, as well as impaired mental and physical health. Preclinical studies have shown that sleep deprivation alters several physiological functions later in life such as the cardiovascular, immune and endocrine systems, resulting in altered oxidative states. Most of the preclinical literature is focused on adult animals, and little is known about oxidative alterations during development, especially in the context of sleep deprivation. Hence, we adapted a classic and well-documented model of sleep deprivation, paradoxical sleep deprivation using multiple platforms, for juvenile rats and explored central and peripheral oxidative parameters, as well as the behavioural consequences of sleep deprivation post-weaning. We showed that 96 h of paradoxical sleep deprivation induced a significant reduction in body weight, decreased sucrose preference-a behaviour suggestive of anhedonia-and increased glucose and decreased cholesterol in the plasma. In the brain, we observed a decrease in reduced glutathione levels in the medial prefrontal cortex and an increase in thiobarbituric acid reactive substance levels in the hypothalamus, indicating oxidative damage in these regions. Taken together, our findings suggest that paradoxical sleep deprivation during development induces anhedonic behaviour and promotes central and peripheral alterations in oxidative parameters.

Assuntos

Encéfalo , Privação do Sono , Ratos , Animais , Privação do Sono/complicações , Desmame , Encéfalo/metabolismo , Estresse Oxidativo , Glutationa/metabolismo

RESUMO

Parkinson's disease (PD) is usually diagnosed through motor symptoms that make the patient incapable of carrying out daily activities; however, numerous non-motor symptoms include olfactory disturbances, constipation, depression, excessive daytime sleepiness, and rapid eye movement at sleep; they begin years before motor symptoms. Therefore, several experimental models have been studied to reproduce several PD functional and neurochemical characteristics; however, no model mimics all the PD motor and non-motor symptoms to date, which becomes a limitation for PD study. It has become increasingly relevant to find ways to study the disease from its slowly progressive nature. The experimental models most frequently used to reproduce PD are based on administering toxic chemical compounds, which aim to imitate dopamine deficiency. The most used toxic compounds to model PD have been 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which inhibit the complex I of the electron transport chain but have some limitations. Another toxic compound that has drawn attention recently is rotenone, the classical inhibitor of mitochondrial complex I. Rotenone triggers the progressive death of dopaminergic neurons and α-synuclein inclusions formation in rats; also, rotenone induces microtubule destabilization. This review presents information about the experimental model of PD induced by rotenone, emphasizing its molecular characteristics beyond the inhibition of mitochondrial complex I.

Assuntos

Doença de Parkinson , Ratos , Animais , Rotenona , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Dopamina/fisiologia , Oxidopamina , Complexo I de Transporte de Elétrons , Modelos Animais de Doenças

RESUMO

BACKGROUND: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. METHODS: Twenty pigs were randomly assigned to Control group (n.ß=.ß10), which received saline solution; or to Sildenafil group (n.ß=.ß10), which received sildenafil orally (100.ßmg). After 30.ßminutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4.ß..g.kg-1.h-1) for 180.ßminutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNF.., IL-1.., IL6, and IL10) and troponin I response. RESULTS: Significant hemodynamic alterations were observed after 30.ßminutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19.ß...ß2.ßmmHg to LPS30 52.ß...ß4.ßmmHg, p.ß<.ß0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411.ß...ß29 to LPS180 334.ß...ß49, p.ß<.ß0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35.ß...ß4.ßmmHg at LPS30, p.ß<.ß0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. CONCLUSION: Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Assuntos

Endotoxemia , Hipertensão Pulmonar , Animais , Suínos , Citrato de Sildenafila/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Endotoxinas/farmacologia , Lipopolissacarídeos/farmacologia , Hemodinâmica

RESUMO

Polymethylmethacrylate (PMMA) is a filler used for aesthetic and/or repair purposes. The response to the implantation of biomaterials varies according to factors related to the patient, the professional responsible for the application and the material used. In vitro and in vivo experimental models have been used to study aspects such as the organism/biomaterial interface and the role of macrophages, dendritic cells and neutrophils. This study aimed to characterize the inflammatory reactions related to polymer concentration, implantation depth and exposure time. Different concentrations of PMMA were implanted in different anatomical planes in mice. The consequences of contact with PMMA, from structural changes to the inflammatory characteristic of tissue damage, were histologically evaluated. The implantation interfered in the morphological structure of the region where it was implanted, expanding it and due to the inflammatory reaction generated, by the presence of the vehicle in the initial phase and by the collagen produced in the chronic phase. The 30% concentration of PMMA induced a greater presence of foreign body giant cells both subcutaneously, at 7, 30 and 90 days after implantation (DAI), and intramuscular at 30DAI. Tissue remodeling was more expressive in the subcutaneous region with significant density of the extracellular matrix at 90DAI. In conclusion, the foreign body reaction resulting from the implantation process acquires different characteristics depending on the anatomical plane and the concentration of implanted product, where the more superficial the implantation plane, the greater the inflammatory reaction. Moreover, PMMA concentration and the depth of implantation did not influence the collagen production.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266.

Assuntos

Materiais Biocompatíveis , Polimetil Metacrilato , Camundongos , Animais

RESUMO

Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

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Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

Assuntos

Feminino , Animais , Ratos , Epilepsia/induzido quimicamente , Epilepsia/veterinária , Modelos Animais , Pilocarpina/administração & dosagem , Pilocarpina/efeitos adversos , Pilocarpina/farmacologia

RESUMO

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the models chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

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Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.