RESUMEN
α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.
RESUMEN
The mechanisms of pathogenesis of acute kidney injury (AKI) in snakebites is multifactorial and involves hemodynamic disturbances, with release of free radical causing cytotoxic effects. The phosphodiesterase-3 (PDE3) inhibitor, Cilostazol, has been reported to provide protection against renal oxidative stress. OBJECTIVE: We evaluated the protective effects of cilostazol against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. METHODS: Wistar rat kidneys (n = 6, 260-300 g) were isolated and perfused with Krebs-Henseleit solution containing 6 g/100 mL of bovine serum albumin. After 30 min, the kidneys were perfused with BaV to a final concentration of 1 and 3 µg/mL, and subsequently evaluated for perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and percentage of electrolyte tubular sodium and chloride transport (%TNa+, %TCl-). Oxidative stress and renal histological analyses were performed. RESULTS: BaV caused a reduction in all the evaluated renal parameters (PP, RVR, GFR, UF, %TNa+, and %TCl-). Although only the effects on PP and UF were reversed with cilostazol treatment, the decrease in the malondialdehyde levels, without changes in glutathione levels, further reduced the venom-induced renal tissue changes. CONCLUSION: Our data suggest that PDE3 is involved in BaV-induced nephrotoxicity, as cilostazol administration significantly ameliorated these effects.
Asunto(s)
Lesión Renal Aguda , Bothrops , Venenos de Crotálidos , Animales , Ratas , Venenos de Crotálidos/farmacología , Cilostazol/farmacología , Inhibidores de Fosfodiesterasa 3/farmacología , Ratas Wistar , Riñón , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Venenos de Serpiente/farmacología , Oxidación-Reducción , Hidrolasas Diéster Fosfóricas/farmacologíaRESUMEN
This study aimed to investigate the synthesis and potential vasodilator effect of a novel ruthenium complex, cis-[Ru(bpy)2(2-MIM)(NO2)]PF6 (bpy = 2,2'-bipyridine and 2-MIM = 2-methylimidazole) (FOR711A), containing an imidazole derivative via an in silico molecular docking model using ß1 H-NOX (Heme-nitric oxide/oxygen binding) domain proteins of reduced and oxidized soluble guanylate cyclase (sGC). In addition, pharmacokinetic properties in the human organism were predicted through computational simulations and the potential for acute irritation of FOR711A was also investigated in vitro using the hen's egg chorioallantoic membrane (HET-CAM). FOR711A interacted with sites of the ß1 H-NOX domain of reduced and oxidized sGC, demonstrating shorter bond distances to several residues and negative values of total energy. The predictive study revealed molar refractivity (RM): 127.65; Log Po/w = 1.29; topological polar surface area (TPSA): 86.26 Å2; molar mass (MM) = 541.55 g/mol; low solubility, high unsaturation index, high gastrointestinal absorption; toxicity class 4; failure to cross the blood-brain barrier and to react with cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4. After the HET-CAM assay, the FOR711A complex was classified as non-irritant (N.I.) and its vasodilator effect was confirmed through greater evidence of blood vessels after the administration and ending of the observation period of 5 min. These results suggest that FOR711A presented a potential stimulator/activator effect of sGC via NO/sGC/cGMP. However, results indicate it needs a vehicle for oral administration.
Asunto(s)
Complejos de Coordinación/química , Óxido Nítrico/química , Rutenio/química , Vasodilatadores/química , Vasodilatadores/farmacología , Animales , Pollos , Membrana Corioalantoides/metabolismo , Hemo/química , Humanos , Imidazoles/química , Simulación del Acoplamiento Molecular/métodos , Óxido Nítrico/metabolismo , Oxígeno/química , Dominios Proteicos , Guanilil Ciclasa Soluble/química , Guanilil Ciclasa Soluble/metabolismoRESUMEN
Background: Hypothyroidism is an endocrine disease that leads to a reduction in the hormones thyroxine (T3) and triiodothyronine (T4), which therapy with levothyroxine restores the clinical signs related to the metabolic rate. Due to the influence of thyroid hormones on the heart, which is under the constant influence of the autonomic nervous system (ANS), dogs with hypothyroidism can develop bradycardia, arrhythmia, and dysautonomia. Heart rate variability (HRV) assesses autonomic modulation by the Holter method, which is scarce in dogs. We aimed to report the cardiac and autonomic effects of the primary hypothyroidism untreated and treated with levothyroxine in a canine case by Holter monitoring. Case: A 7-year-old female Dalmatian, weighing 36 kg, was referred for clinical evaluation due to apathy, weight gain, low hair quality, and lethargy. On physical examination, alopecic lesions on the hind limbs and tail, as well as bradycardia with a heart rate (HR) of 40-50 beats per minute (bpm) were observed, in addition to a 3/6 mitral murmur and 2/6 tricuspid murmur. Given the suspicion of thyroid gland disorder, the blood hormonal measurement revealed an increase in thyroidstimulating hormone (TSH; 0.65 ng/mL) and a decrease in free T4 (0.11 ng/mL) and total T4 (0.44 ng/mL), confirming primary hypothyroidism. Therapy was started with a minimum dose of levothyroxine (0.913 mg, every 12 h), which clinical signs were restored in 5 months of treatment, with weight loss, hair growth, and active behavior. To assess the impact of untreated and treated hypothyroidism on the patients ANS, a Holter monitoring exam was performed for 24 h before and after therapy. Before treatment, the average HR was 75 bpm, and the HR<50 bpm occurred during 05 h 20 min 36 s. Still, 320 pause events (>2.0s), 1st-degree atrioventricular blocks (AVB), six...(AU)
Asunto(s)
Animales , Femenino , Perros , Dosificación/métodos , Tiroxina/administración & dosificación , Tiroxina/uso terapéutico , Hipotiroidismo/veterinaria , Disautonomías Primarias/veterinaria , Electrocardiografía Ambulatoria/veterinaria , Sistema Nervioso AutónomoRESUMEN
Background: Hypothyroidism is an endocrine disease that leads to a reduction in the hormones thyroxine (T3) and triiodothyronine (T4), which therapy with levothyroxine restores the clinical signs related to the metabolic rate. Due to the influence of thyroid hormones on the heart, which is under the constant influence of the autonomic nervous system (ANS), dogs with hypothyroidism can develop bradycardia, arrhythmia, and dysautonomia. Heart rate variability (HRV) assesses autonomic modulation by the Holter method, which is scarce in dogs. We aimed to report the cardiac and autonomic effects of the primary hypothyroidism untreated and treated with levothyroxine in a canine case by Holter monitoring. Case: A 7-year-old female Dalmatian, weighing 36 kg, was referred for clinical evaluation due to apathy, weight gain, low hair quality, and lethargy. On physical examination, alopecic lesions on the hind limbs and tail, as well as bradycardia with a heart rate (HR) of 40-50 beats per minute (bpm) were observed, in addition to a 3/6 mitral murmur and 2/6 tricuspid murmur. Given the suspicion of thyroid gland disorder, the blood hormonal measurement revealed an increase in thyroidstimulating hormone (TSH; 0.65 ng/mL) and a decrease in free T4 (0.11 ng/mL) and total T4 (0.44 ng/mL), confirming primary hypothyroidism. Therapy was started with a minimum dose of levothyroxine (0.913 mg, every 12 h), which clinical signs were restored in 5 months of treatment, with weight loss, hair growth, and active behavior. To assess the impact of untreated and treated hypothyroidism on the patients ANS, a Holter monitoring exam was performed for 24 h before and after therapy. Before treatment, the average HR was 75 bpm, and the HR2.0s), 1st-degree atrioventricular blocks (AVB), six...
Asunto(s)
Femenino , Animales , Perros , Disautonomías Primarias/veterinaria , Dosificación/métodos , Hipotiroidismo/veterinaria , Tiroxina/administración & dosificación , Tiroxina/uso terapéutico , Electrocardiografía Ambulatoria/veterinaria , Sistema Nervioso AutónomoRESUMEN
Background: Thyroid hormones have important effects on the cardiovascular system, of which the main ones are the in-crease in the heart response to the autonomic sympathetic nervous system. Heart rate variability is a non-invasive method of assessing autonomic heart modulation, thus being an important form of evaluation in patients with thyroid dysfunctions. This study aimed to report electrocardiographic and heart rate variability data of a dog with hypothyroidism that presented a parasympathetic dysfunction.Case:A 7-year-old female Dalmatian dog was admitted for clinical evaluation in Fortaleza, Brazil. According to the owner, she had been apathetic for a year, had gained weight, always had a sad expression, and her hair was generally brittle and opaque. On physical examination, skin lesions were observed at the end of the spine, extending to the tail region, with the latter showing total alopecia. Low T4 levels confirmed the diagnosis of primary hypothyroidism. Then, a 24-h Holter monitoring was performed, which showed that the animal had sinus arrhythmia associated with moments of second-degree sinoatrial block and rare moments of sinus tachycardia. In addition, moments of premature multifocal ventricular extra-systoles and 1st-degree atrioventricular block were observed.Based on the Holter results, heart rate variability (HRV) was calculated. Regarding the HRV in the frequency domain, 32.16 was obtained in the low frequency (LF) band, 67.84 in the high frequency (HF) band, and the LF / HF ratio was 0.46, with a total power of 5205. As for the HRV in the time domain, RMSSD was 117, pNN50 was 62.64 and SDNN was 384. This showed an increase in the parasympathetic activity of the heart and, due to this increased activity, a...
Asunto(s)
Femenino , Animales , Perros , Disautonomías Primarias/diagnóstico , Disautonomías Primarias/veterinaria , Hipotiroidismo/veterinaria , Bloqueo Atrioventricular/veterinaria , Bloqueo Sinoatrial/veterinaria , Electrocardiografía/veterinariaRESUMEN
Background: Thyroid hormones have important effects on the cardiovascular system, of which the main ones are the in-crease in the heart response to the autonomic sympathetic nervous system. Heart rate variability is a non-invasive method of assessing autonomic heart modulation, thus being an important form of evaluation in patients with thyroid dysfunctions. This study aimed to report electrocardiographic and heart rate variability data of a dog with hypothyroidism that presented a parasympathetic dysfunction.Case:A 7-year-old female Dalmatian dog was admitted for clinical evaluation in Fortaleza, Brazil. According to the owner, she had been apathetic for a year, had gained weight, always had a sad expression, and her hair was generally brittle and opaque. On physical examination, skin lesions were observed at the end of the spine, extending to the tail region, with the latter showing total alopecia. Low T4 levels confirmed the diagnosis of primary hypothyroidism. Then, a 24-h Holter monitoring was performed, which showed that the animal had sinus arrhythmia associated with moments of second-degree sinoatrial block and rare moments of sinus tachycardia. In addition, moments of premature multifocal ventricular extra-systoles and 1st-degree atrioventricular block were observed.Based on the Holter results, heart rate variability (HRV) was calculated. Regarding the HRV in the frequency domain, 32.16 was obtained in the low frequency (LF) band, 67.84 in the high frequency (HF) band, and the LF / HF ratio was 0.46, with a total power of 5205. As for the HRV in the time domain, RMSSD was 117, pNN50 was 62.64 and SDNN was 384. This showed an increase in the parasympathetic activity of the heart and, due to this increased activity, a...(AU)
Asunto(s)
Animales , Femenino , Perros , Disautonomías Primarias/diagnóstico , Disautonomías Primarias/veterinaria , Hipotiroidismo/veterinaria , Bloqueo Atrioventricular/veterinaria , Bloqueo Sinoatrial/veterinaria , Electrocardiografía/veterinariaRESUMEN
Background: Boxer dog cardiomyopathy was initially described by Neil Harpster in 1983 and has received different names. However, several recent studies demonstrated a similarity to the human arrhythmogenic right ventricular cardiomyopathy (ARVC), which led to the name Boxer ARVC. This hereditary disease seems to be linked to a mutation in the gene that codifies the cardiac ryanodine receptor. This mutation leads to an alteration of the calcium cycle in the heart. The analysis of the heart rate variability is an important predictive factor for diagnosing this disease. Therefore, this study aims to report a case of a Boxer ARVC providing electrocardiographic data and heart rate variability.Case: A 11 year-old male Boxer dog, weighting 29.65 kg, was submitted to a heart check-up due to sudden occurrence of fatigue and syncope. At the clinical examination, heart auscultation did not revealed sounds or arrhythmias. The electrocardiogram results presented tachycardia and a regular rhythm with ventricular premature complexes (VPC´s). Ecodopplercargiogram was performed and values were within normal standards. Thus, a dynamic monitoring of 24 h was performed using a Holter monitor. This analysis demonstrated tachycardia in the sinus rhythm, type I second degree sinoatrial block, normal PR interval and normal length of QRS complexes. In addition, severe ventricular ectopy was identified in the following forms: isolated, paired, and nonsustained ventricular tachycardia. The heart rate variability analysis resulted in mean values of 213 ms (SNDD), 132 ms (SDANN), 211ms (rMSSD) and 33.46% (pNN50). Based on these data, Boxer ARVC is the probable diagnosis. However, a ventricular myocardial biopsy necessary to confirm the disease was not performed due to the inherent risk of the procedure. Treatment was performed with sotalol and a commercial feed specially designed for dogs with for cardiac diseases.[...]
Asunto(s)
Masculino , Animales , Adulto , Perros , Displasia Ventricular Derecha Arritmogénica/diagnóstico por imagen , Displasia Ventricular Derecha Arritmogénica/veterinaria , Frecuencia Cardíaca , Electrocardiografía Ambulatoria/métodos , Electrocardiografía Ambulatoria/veterinariaRESUMEN
Background: Boxer dog cardiomyopathy was initially described by Neil Harpster in 1983 and has received different names. However, several recent studies demonstrated a similarity to the human arrhythmogenic right ventricular cardiomyopathy (ARVC), which led to the name Boxer ARVC. This hereditary disease seems to be linked to a mutation in the gene that codifies the cardiac ryanodine receptor. This mutation leads to an alteration of the calcium cycle in the heart. The analysis of the heart rate variability is an important predictive factor for diagnosing this disease. Therefore, this study aims to report a case of a Boxer ARVC providing electrocardiographic data and heart rate variability.Case: A 11 year-old male Boxer dog, weighting 29.65 kg, was submitted to a heart check-up due to sudden occurrence of fatigue and syncope. At the clinical examination, heart auscultation did not revealed sounds or arrhythmias. The electrocardiogram results presented tachycardia and a regular rhythm with ventricular premature complexes (VPC´s). Ecodopplercargiogram was performed and values were within normal standards. Thus, a dynamic monitoring of 24 h was performed using a Holter monitor. This analysis demonstrated tachycardia in the sinus rhythm, type I second degree sinoatrial block, normal PR interval and normal length of QRS complexes. In addition, severe ventricular ectopy was identified in the following forms: isolated, paired, and nonsustained ventricular tachycardia. The heart rate variability analysis resulted in mean values of 213 ms (SNDD), 132 ms (SDANN), 211ms (rMSSD) and 33.46% (pNN50). Based on these data, Boxer ARVC is the probable diagnosis. However, a ventricular myocardial biopsy necessary to confirm the disease was not performed due to the inherent risk of the procedure. Treatment was performed with sotalol and a commercial feed specially designed for dogs with for cardiac diseases.[...](AU)
Asunto(s)
Animales , Masculino , Adulto , Perros , Displasia Ventricular Derecha Arritmogénica/diagnóstico por imagen , Displasia Ventricular Derecha Arritmogénica/veterinaria , Frecuencia Cardíaca , Electrocardiografía Ambulatoria/métodos , Electrocardiografía Ambulatoria/veterinariaRESUMEN
Background: The malignant neoplasms, in general, constitute one of the main causes of death in dogs and cats. The multiple myeloma is a neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, causing several systemic symptoms and it is rare in pets, representing less than 1% of the malignant neoplasms in these animals. It usually occurs in older dogs. Thus, the purpose of this report was to describe a case of multiple myeloma in a 10-year-old poodle dog, occurred in the Veterinary Hospital Unit of the State University of Ceará. Case: A 10-year-old Poodle bitch was admitted in the Veterinary Hospital Unit of the State University of Ceará presenting lump erythematosus, alopecic, soft and ulcers in the region of the digits of the left front leg, pain and lameness. The blood count evidenced normocytic and normochromic anemia, presence of rouleaux, lymphopenia and monocytopenia, and the biochemical exams have demonstrated an elevated value of alanine aminotransferase (ALT). The cytology of the nodule indicated probable diagnosis of plasma cell neoplasm and radiographic examination showed the presence of bone lysis, and therefore the patient underwent amputation of the affected limb surgery. A biopsy of the nodule indicated neoplastic proliferation, with an arrange compatible to plasmacytoma of cleaved type. A follow-up consultation was realized 30 days after surgery, and 2 new nodules appeared in the superior lip region and close to the surgery site. A new blood count indicated anemia with presence of rouleaux, thrombocytopenia, leucopenia, lymphopenia and monocytopenia, and the biochemical results showed a discrete diminution of aspartate aminotransferase(AST) and a considerable increase on the alkaline phosphatase levels. The cytology of the new nodules indicated plasmacytoma, and was realized a myelogram, that showed dysplastic marrow plasma cells, with more than 20% of plasma cells...
Asunto(s)
Femenino , Animales , Perros , Alanina Transaminasa , Aspartato Aminotransferasas , Mieloma Múltiple/veterinaria , Células Plasmáticas , Mielografía/veterinariaRESUMEN
Background: The malignant neoplasms, in general, constitute one of the main causes of death in dogs and cats. The multiple myeloma is a neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, causing several systemic symptoms and it is rare in pets, representing less than 1% of the malignant neoplasms in these animals. It usually occurs in older dogs. Thus, the purpose of this report was to describe a case of multiple myeloma in a 10-year-old poodle dog, occurred in the Veterinary Hospital Unit of the State University of Ceará. Case: A 10-year-old Poodle bitch was admitted in the Veterinary Hospital Unit of the State University of Ceará presenting lump erythematosus, alopecic, soft and ulcers in the region of the digits of the left front leg, pain and lameness. The blood count evidenced normocytic and normochromic anemia, presence of rouleaux, lymphopenia and monocytopenia, and the biochemical exams have demonstrated an elevated value of alanine aminotransferase (ALT). The cytology of the nodule indicated probable diagnosis of plasma cell neoplasm and radiographic examination showed the presence of bone lysis, and therefore the patient underwent amputation of the affected limb surgery. A biopsy of the nodule indicated neoplastic proliferation, with an arrange compatible to plasmacytoma of cleaved type. A follow-up consultation was realized 30 days after surgery, and 2 new nodules appeared in the superior lip region and close to the surgery site. A new blood count indicated anemia with presence of rouleaux, thrombocytopenia, leucopenia, lymphopenia and monocytopenia, and the biochemical results showed a discrete diminution of aspartate aminotransferase(AST) and a considerable increase on the alkaline phosphatase levels. The cytology of the new nodules indicated plasmacytoma, and was realized a myelogram, that showed dysplastic marrow plasma cells, with more than 20% of plasma cells...(AU)