Alonso Gabriel Pereira Guedes

Reparação do ligamento cruzado cranial de cães por tendão homólogo conservado em glicerina e associado a fio de náilon

Rupture of the cranial cruciate ligament (CCL) is one of the most prevalent stifle diseases in dogs and its therapy is a problem today. The purpose of this report was to evaluate the response to long digital extensor muscle tendon preserved in glycerol as a substitute of the cranial cruciate ligament in dogs. The technique was performed in 18 mongrel dogs, with mean body weight of 16.5kg, and evaluated until 45, 80 or 120 postoperative days. Clinic, radiographic, macroscopic and histologic studies were done. The technique was efficient to return to normal gait determining good articular stability, although the biologic implant was absent in most animals and the mononylon was not taut.

Inhibition of soluble epoxide hydrolase attenuates eosinophil recruitment and food allergen‐induced gastrointestinal inflammation

Prevalence of food allergies in the United States is on the rise. Eosinophils are recruited to the intestinal mucosa in substantial numbers in food allergen‐driven gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to play a pro‐inflammatory role during inflammation by metabolizing anti‐inflammatory epoxyeicosatrienoic acids (EETs) to pro‐inflammatory diols. We investigated the role of sEH in a murine model of food allergy and evaluated the potential therapeutic effect of a highly selective sEH inhibitor (trans‐4‐{4‐[3‐(4‐trifluoromethoxyphenyl)‐ureido]‐cyclohexyloxy}‐benzoic acid [t‐TUCB]). Oral exposure of mice on a soy‐free diet to soy protein isolate (SPI) induced expression of intestinal sEH, increased circulating total and antigen‐specific IgE levels, and caused significant weight loss. Administration of t‐TUCB to SPI‐challenged mice inhibited IgE levels and prevented SPI‐induced weight loss. Additionally, SPI‐induced GI inflammation characterized by increased recruitment of eosinophils and mast cells, elevated eotaxin 1 levels, mucus hypersecretion, and decreased epithelial junction protein expression. In t‐TUCB‐treated mice, eosinophilia, mast cell recruitment, and mucus secretion were significantly lower than in untreated mice and SPI‐induced loss of junction protein expression was prevented to variable levels. sEH expression in eosinophils was induced by inflammatory mediators TNF‐α and eotaxin‐1. Treatment of eosinophils with t‐TUCB significantly inhibited eosinophil migration, an effect that was mirrored by treatment with 11,12‐EET, by inhibiting intracellular signaling events such as ERK (1/2) activation and eotaxin‐1‐induced calcium flux. These studies suggest that sEH induced by soy proteins promotes allergic responses and GI inflammation including eosinophilia and that inhibition of sEH can attenuate these responses.

Evaluation of tramadol for treatment of osteoarthritis in geriatric cats

OBJECTIVE To evaluate tramadol for treatment of signs of pain and impaired mobility in geriatric cats with osteoarthritis. DESIGN Randomized controlled crossover trial. ANIMALS 24 client-owned geriatric (≥ 10 years old) cats with osteoarthritis. PROCEDURES Otherwise healthy cats with owner-identified mobility impairment and clinical and radiographic evidence of osteoarthritis involving at least 1 appendicular joint were enrolled in the study. Cats were treated with tramadol orally at dosages of 0 (placebo), 1, 2, and 4 mg/kg (0, 0.45, 0.9, and 1.8 mg/lb) twice a day for 5 days, with a 2-day (weekend) washout period between treatments. Mobility was assessed with a collar-mounted activity monitor system, and impairments in activity were assessed with a client-completed questionnaire. RESULTS 17 cats completed the study; 7 cats were withdrawn. There was a significant increase in activity with the 2-mg/kg dosage of tramadol, compared with activity when cats received the placebo. Significantly more owners (11/18) considered their cats to have improved with the 2-mg/kg treatment, compared with all other dosages (6/19 to 8/21). Most owners (17/20 [85%]) considered their cats global quality of life to have improved during the study. Adverse events, predominantly euphoria, dysphoria, sedation, decreased appetite, and diarrhea, were significantly more frequent with the 4-mg/kg (8/19) and 2-mg/kg (6/18) treatments but not with the 1-mg/kg (2/21) treatment, compared with frequency of adverse events with the placebo (0/21). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a beneficial effect of twice-daily oral administration of tramadol at a dosage of 2 mg/kg in geriatric cats with osteoarthritis. Adverse events were dose dependent, and caution should be exercised in cats that have concurrent disease or are receiving other drugs that may produce adverse gastrointestinal effects.

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic geriatric cats

OBJECTIVE Toevaluate effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life (QOL) in osteoarthritic geriatric cats. DESIGN Blinded, placebo-controlled, randomized crossover-design study. ANIMALS 20 osteoarthritic cats (≥ 10 years old). PROCEDURES Cats received gabapentin (10 mg/kg [4.5 mg/lb]) or placebo treatment, PO, every 12 hours for 2 weeks, followed by the alternate treatment (with no washout period). Activity was assessed with a collar-mounted accelerometer. A client-specific outcome measure (CSOM) questionnaire was used weekly to collect owner assessments of 3 selected activities in which their cats had impaired mobility; QOL ratings (worse, the same, or improved) following crossover to each treatment and for the overall study period were collected at the end of the investigation. Activity counts, CSOM and QOL data, and deterioration in impaired activities (ie, decrease of ≥ 2 points in CSOM scores) associated with treatment crossover were assessed statistically. Adverse events were recorded. RESULTS Gabapentin administration was associated with significantly lower mean daily activity counts (48,333 vs 39,038 counts/d) and significantly greater odds (approx 3-fold change) of CSOM ratings indicating improvement in impaired activities, compared with results for the placebo treatment. A greater proportion of cats had deterioration in impaired activities after the crossover from gabapentin to placebo than when the opposite occurred, but the proportion of cats with worsened QOL did not differ between sequences. Adverse events were noted for 10 cats (9 that completed the study) during gabapentin treatment (sedation, ataxia, weakness, and muscle tremors) and 1 cat during placebo treatment (lethargy). CONCLUSIONS AND CLINICAL RELEVANCE Gabapentin treatment was associated with improvement in owner-identified impaired activities of osteoarthritic cats. Activity levels were lower than those during placebo treatment, and sedation was the most common adverse effect.