New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders.

Nitrosyl ruthenium complexes are promising platforms for nitric oxide (NO) and nitroxyl (HNO) release, which exert their therapeutic application. In this context, we developed two polypyridinic compounds with the general formula cis-[Ru(NO)(bpy)2(L)]n+, where L is an imidazole derivative. These species were characterized by spectroscopic and electrochemical techniques, including XANES/EXAFS experiments, and further supported by DFT calculations. Interestingly, assays using selective probes evidenced that both complexes can release HNO on reaction with thiols. This finding was biologically validated by HIF-1α detection. The latter protein is related to angiogenesis and inflammation processes under hypoxic conditions, which is selectively destabilized by nitroxyl. These metal complexes also presented vasodilating properties using isolated rat aorta rings and demonstrated antioxidant properties in free radical scavenging experiments. Based on these results, the new nitrosyl ruthenium compounds showed promising characteristics as potential therapeutic agents for the treatment of cardiovascular conditions such as atherosclerosis, deserving further investigation.

Synthesis and potential vasorelaxant effect of a novel ruthenium-based nitro complex.

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.

Phosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom.

Acute kidney injury pathogenesis in envenoming by snakes is multifactorial and involves immunologic reactions, hemodynamic disturbances, and direct nephrotoxicity. Sildenafil (SFC), a phosphodiesterase 5 inhibitor, has been reported to protect against pathological kidney changes. OBJECTIVE: This study aimed to investigate the protective effect of sildenafil against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. METHODS: Kidneys from Wistar rats (n = 6, weighing 260-300 g) were isolated and divided into four groups: (1) perfused with a modified Krebs-Henseleit solution (MKHS) containing 6 g% of bovine serum albumin; (2) administered 3 µg/mL SFC; (3) perfused with 3 µg/mL BaV; and (4) administered SFC + BaV, both at 3 µg/mL. Subsequently, the 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-, respectively) were evaluated. The cyclic guanosine monophosphate (cGMP) levels were analyzed in the perfusate, and the kidneys were removed to perform oxidative stress and histopathological analyses. RESULTS: All renal parameters evaluated were reduced with BaV. In the SFC + BaV group, SFC restored PP to normal values and promoted a significant increase in %TNa+ and %TCl-. cGMP levels were increased in the SFC + BaV group. The oxidative stress biomarkers, malondialdehyde (MDA) and glutathione (GSH), were reduced by BaV. In the SFC + BaV group, a decrease in MDA without an increase in GSH was observed. These findings were confirmed by histological analysis, which showed improvement mainly in tubulis. CONCLUSION: Our data suggest the involvement of phosphodiesterase-5 and cGMP in BaV-induced nephrotoxicity since its effects were attenuated by the administration of SFC.

Bothrops pauloensis snake venom-derived Asp-49 and Lys-49 phospholipases A2 mediates acute kidney injury by oxidative stress and release of inflammatory cytokines.

The envenomation caused by the Bothrops pauloensis snake leads to severe local and systemic effects including acute kidney injury. In this study, we investigated the renal effects by phospholipases A2 (PLA2s), divided into two main subgroups, Asp-49 and Lys-49, isolated from the Bothrops pauloensis snake venom (BpV) in isolated rat kidney system. Both PLA2s (3 µg/mL), added alone to the perfusion system and analyzed for 120 min, had significant effects on isolated rat kidney. Asp-49 reduced Glomerular Filtration Rate (GFR) at 60, 90 and 120 min, and the percentage of total tubular sodium transport (%TNa+) and potassium transport (%TK+) at 120 min. Lys-49 increased Perfusion Pressure (PP) at 120 min and reduced GFR, %TNa+ and the percentage of total tubular chloride transport (%TCl-) at 60, 90 and 120 min. Cytokine release in the kidney tissues were increased with Asp-49 PLA2 (IL-10) and Lys-49 PLA2 (TNF-α, IL-1ß, IL-10). Both increased MPO activity. Asp-49 PLA2 decreased Glutathione (GSH) and increased nitrite levels, while Lys-49 PLA2 increased Malondialdehyde (MDA), GSH and nitrite levels. Histological analysis of the perfused kidneys revealed the presence of glomerular degeneration and atrophy, deposit of proteinaceous material in Bowman's space and intratubular with both PLA2s. These findings indicated that both PLA2s modified the functional parameters in an isolated perfused kidney model with increased oxidative stress and cytokine release. PLA2s are one of the components at high concentration in BpV and our results provide important knowledge about their involvement with the nephrotoxic mechanism.

In silico study of azithromycin, chloroquine and hydroxychloroquine and their potential mechanisms of action against SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is a highly transmissible viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials have reported improved outcomes resulting from an effective reduction or absence of viral load when patients were treated with chloroquine (CQ) or hydroxychloroquine (HCQ). In addition, the effects of these drugs were improved by simultaneous administration of azithromycin (AZM). The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein binds to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor, allowing virus entry and replication in host cells. The viral main protease (Mpro) and host cathepsin L (CTSL) are among the proteolytic systems involved in SARS-CoV-2 S protein activation. Hence, molecular docking studies were performed to test the binding performance of these three drugs against four targets. The findings showed AZM affinity scores (ΔG) with strong interactions with ACE2, CTSL, Mpro and RBD. CQ affinity scores showed three low-energy results (less negative) with ACE2, CTSL and RBD, and a firm bond score with Mpro. For HCQ, two results (ACE2 and Mpro) were firmly bound to the receptors, however CTSL and RBD showed low interaction energies. The differences in better interactions and affinity between HCQ and CQ with ACE2 and Mpro were probably due to structural differences between the drugs. On other hand, AZM not only showed more negative (better) values in affinity, but also in the number of interactions in all targets. Nevertheless, further studies are needed to investigate the antiviral properties of these drugs against SARS-CoV-2.

Renal effects of venoms of Mexican coral snakes Micrurus browni and Micrurus laticollaris.

The Micrurus snake venoms mainly cause systemic complications, essentially neurotoxicity. Previous studies, however, have described that they are involved in the occurrence of acute kidney injury (AKI) in animal models. AKI pathogenesis in snakebites is multifactorial and involves immunological reactions, hemodynamic disturbances, and direct nephrotoxicity. The aim of this study was to compare the nephrotoxic effects of coral snake venoms from M. browni (MbV) and M. laticollaris (MlV) on the proximal tubular epithelial cell line (LLC-MK2) and isolated perfused kidney. Using an MTT assay, both venoms significantly reduced cell viability at higher concentrations (25-100 µg/mL). MlV (10 µg/mL) increased the perfusion pressure (PP) at 60, 90 and 120 min, while the MbV did it only at 90 and 120 min. Renal vascular resistance (RVR) decreased at 60 min and increased at 120 min with MbV, but decreased at 60, 90 and 120 min with MlV. Urinary flow (UF) alterations were not observed with MlV, but MbV elevated them at 90 and 120 min. Both venoms significantly decreased the glomerular filtration rate (GFR), %TNa+, %TK+ and %TCl- levels as of 60 min of perfusion. Oxidative stress analysis revealed that both venoms behaved similarly, reducing glutathione and increasing malondialdehyde levels. Kidney injury is not usually described in clinical cases of Micrurus snakebites. However, the potential for nephrotoxicity should be considered in the overall picture of envenomation.

Pulmonary mechanic and lung histology induced by Crotalus durissus cascavella snake venom.

This study have analyzed the pulmonary function in an experimental model of acute lung injury, induced by the Crotalus durissus cascavella venom (C. d. cascavella) (3.0 µg/kg - i.p), in pulmonary mechanic and histology at 1 h, 3 h, 6 h, 12 h and 24 h after inoculation. The C. d. cascavella venom led to an increase in Newtonian Resistance (RN), Tissue Resistance (G) and Tissue Elastance (H) in all groups when compared to the control, particularly at 12 h and 24 h. The Histeresivity (η) increased 6 h, 12 h and 24 h after inoculation. There was a decrease in Static Compliance (CST) at 6 h, 12 h and 24 h and inspiratory capacity (IC) at 3 h, 6 h, 12 h and 24 h. C. d. cascavella venom showed significant morphological changes such as atelectasis, emphysema, hemorrhage, polymorphonuclear inflammatory infiltrate, edema and congestion. After a challenge with methacholine (MCh), RN demonstrated significant changes at 6, 12 and 24 h. This venom caused mechanical and histopathological changes in the lung tissue; however, its mechanisms of action need further studies in order to better elucidate the morphofunctional lesions.

Differences between renal effects of venom from two Bothrops jararaca populations from southeastern and southern Brazil.

Components from animal venoms may vary according to the snake's age, gender and region of origin. Recently, we performed a proteomic analysis of Bothrops jararaca venom from southern (BjSv) and southeastern (BjSEv) Brazil, showing differences in the venom composition, as well as its biological activity. To continue the study, we report in this short communication the different effects induced by the BjSEv and BjSv on isolated kidney and MDCK renal cells. BjSEv decreased perfusion pressure (PP) and renal vascular resistance (RVR) and increased urinary flow (UF) and glomerular filtration rate (GFR), while BjSv did not alter PP and RVR and reduced UF and GFR. Both types of venom, more expressively BjSEv, reduced %TNa+, %TK+ and %Cl-. In MDCK cells, the two types of venom showed cytotoxicity with IC50 of 1.22 µg/mL for BjSv and 1.18 µg/mL for BjSEv and caused different profiles of cell death, with BjSv being more necrotic. In conclusion, we suggest that BjSv is more nephrotoxic than BjSEv.

Hipertensão arterial sistêmica em gatos / Systemic arterial hypertension in cats

A hipertensão arterial sistólica é frequentemente reconhecida na prática clínica da medicina interna felina, sendo um problema comum em gatos mais velhos. Esta enfermidade é, costumeiramente, secundária a outras doenças, tais como, doença renal crônica e hipertireoidismo. No entanto, em alguns pacientes a causa subjacente não é identificada, portanto denominada de hipertensão idiopática. Elevações na pressão arterial, de forma sustentada ou não, podem levar a danos em diversos órgãos como, cérebro, olhos, coração e rins. Essas injúrias são denominadas de lesão de órgãos-alvo. Pressão arterial sistêmica acima de 160mmHg possue risco moderado a grave de dano aos órgãos-alvo. Desta maneira, o tratamento procura idealmente atingir riscos de dano mínimos. Alguns fármacos podem ser utilizados como terapia anti-hipertensiva, dentre elas, a amlodipina, um bloqueador de canal de cálcio, que é o medicamento de primeira escolha para tratamento em gatos. Além disso, é de extrema importância o diagnóstico de doenças que possam gerar o quadro hipertensivo ou estar em associação para que desta forma seja possível um controle adequado da pressão arterial. O diagnóstico precoce da doença é fundamental pois auxilia reduzir as chances de lesão nos órgãos-alvo, e consequentemente, reduz a mortalidade e melhora a qualidade de vida dos pacientes.

Systolic arterial hypertension is often recognized in the clinical practice of feline internal medicine and is a common problem in older cats. This disease is usually secondary to other diseases, such as chronic kidney disease and hyperthyroidism. However, in some patients the underlying cause is not identified, therefore called idiopathic hypertension. Elevations in blood pressure, whether sustained or not, can cause damage to various organs such as the brain, eyes, heart and kidneys. These injuries are called target organ damage. Systemic blood pressure above 160mmHg has a moderate to severe risk of damage to target organs. In this way, the treatment ideally seeks to achieve risks of cognitive damage. Pharmacological substances can be used as antihypertensive therapy, among them, an amlodipine, a calcium channel blocker, which is the drug of choice for treatment in cats. In addition, it is extremely important to diagnose diseases that cause hypertension or to be associated with it, so that this form of blood pressure is adequate. Early diagnosis of the disease is essential because it helps to reduce the chances of target organ damage, and consequently, reduce mortality and improve patients' quality of life.

Picrosirius red and Massons Trichrome staining techniques as tools for detection of collagen fibers in the skin of dogs with endocrine dermatopathologies / Picrosirius red e Tricrômico de Masson como ferramentas para detecção de fibras colágenas em pele de cães com dermatopatologias endócrinas

Canine endocrinopathies, such as hypothyroidism and hyperadrenocortism,induce typical dermatological alterations. Collagen fibers are significant for the maintenance of structural integrity,as well as in the determination of tissue function. This study aimed at assessing the coloration caused by Picrosirius Red staining under circular polarization and Masson Trichrome staining, as tools to quantify the total collagen in the skin of dogs exhibiting endocrine dermatopathies. Skin samples taken from dogs with hypothyroidism and hyperadrenocorticism were stained using Hematoxylin and Eosin (HE), Massons Trichrome (MT) and Picrosirius Red (PSR). The animals with hyperadrenocorticism revealed a higher percentage of collagen area than did the animals with hypothyroidism PSRp (hypothyroidism = 43.76 ± 0.8255 and hyperadrenocorticism = 47.08 ± 0.8584). The percentage of the collagen area using MT between the groups is given in parenthesis (hypothyroidism = 52.06 ± 0.9371, hyperadrenocorticism = 61 ± 0.7529 and control = 56.88 ± 0.64) (p <0.05). It is therefore, evident that the special stains employed are useful in estimating the percentage of collagen area in the skin, as they revealed that dogs with hypothyroidism had lower collagen deposition whereas those animals with hyperadrenocorticism showed higher quantity of collagen in the dermis.(AU)

Endocrinopatias caninas como hipotireoidismo e o hiperadrenocortismo causam alterações dermatológicas características. As fibras de colágeno desempenham um papel vital na manutenção da integridade estrutural e também na determinação da função dos tecidos. O objetivo deste estudo foi avaliar as colorações de picrosirius red sob polarização circular e coloração tricômio de Masson como ferramentas para quantificar o colágeno total da pele de cães com dermatopatias endócrinas. Amostras de pele obtidas de cães com hipotireoidismo e hiperadrenocorticismo foram coradas por Hematoxilina e Eosina (HE), Tricrômio de Masson (MT) e Picrosirius red (PSR). A porcentagem de área de colágeno foi maior nos animais com hiperadrenocorticismo e menor nos animais com hipotireoidismo PSRp (hipotireoidismo = 43,76 ± 0.8255 e hiperadrenocorticismo = 47,08 ± 0.8584). Já a porcentagem de área de colágeno no MT entre os grupos (hipotireoidismo = 52,06 ± 0.9371, hiperadrenocorticismo = 61 ± 0,7529 e controle = 56,88 ± 0.64) (p <0.05). Concluiu-se que as colorações especiais utilizadas são úteis para avaliar a porcentagem de área de colágeno na pele, pois demonstraram que cães com hipotireoidismo demonstraram uma diminuição na deposição de colágeno e os animais com hiperadrenocorticismo apresentaram maior quantidade de colágeno na derme.(AU)

Picrosirius red and Masson’s Trichrome staining techniques as tools for detection of collagen fibers in the skin of dogs with endocrine dermatopathologies / Picrosirius red e Tricrômico de Masson como ferramentas para detecção de fibras colágenas em pele de cães com dermatopatologias endócrinas

Canine endocrinopathies, such as hypothyroidism and hyperadrenocortism,induce typical dermatological alterations. Collagen fibers are significant for the maintenance of structural integrity,as well as in the determination of tissue function. This study aimed at assessing the coloration caused by Picrosirius Red staining under circular polarization and Masson Trichrome staining, as tools to quantify the total collagen in the skin of dogs exhibiting endocrine dermatopathies. Skin samples taken from dogs with hypothyroidism and hyperadrenocorticism were stained using Hematoxylin and Eosin (HE), Masson’s Trichrome (MT) and Picrosirius Red (PSR). The animals with hyperadrenocorticism revealed a higher percentage of collagen area than did the animals with hypothyroidism PSRp (hypothyroidism = 43.76 ± 0.8255 and hyperadrenocorticism = 47.08 ± 0.8584). The percentage of the collagen area using MT between the groups is given in parenthesis (hypothyroidism = 52.06 ± 0.9371, hyperadrenocorticism = 61 ± 0.7529 and control = 56.88 ± 0.64) (p <0.05). It is therefore, evident that the special stains employed are useful in estimating the percentage of collagen area in the skin, as they revealed that dogs with hypothyroidism had lower collagen deposition whereas those animals with hyperadrenocorticism showed higher quantity of collagen in the dermis.

Endocrinopatias caninas como hipotireoidismo e o hiperadrenocortismo causam alterações dermatológicas características. As fibras de colágeno desempenham um papel vital na manutenção da integridade estrutural e também na determinação da função dos tecidos. O objetivo deste estudo foi avaliar as colorações de picrosirius red sob polarização circular e coloração tricômio de Masson como ferramentas para quantificar o colágeno total da pele de cães com dermatopatias endócrinas. Amostras de pele obtidas de cães com hipotireoidismo e hiperadrenocorticismo foram coradas por Hematoxilina e Eosina (HE), Tricrômio de Masson (MT) e Picrosirius red (PSR). A porcentagem de área de colágeno foi maior nos animais com hiperadrenocorticismo e menor nos animais com hipotireoidismo PSRp (hipotireoidismo = 43,76 ± 0.8255 e hiperadrenocorticismo = 47,08 ± 0.8584). Já a porcentagem de área de colágeno no MT entre os grupos (hipotireoidismo = 52,06 ± 0.9371, hiperadrenocorticismo = 61 ± 0,7529 e controle = 56,88 ± 0.64) (p <0.05). Concluiu-se que as colorações especiais utilizadas são úteis para avaliar a porcentagem de área de colágeno na pele, pois demonstraram que cães com hipotireoidismo demonstraram uma diminuição na deposição de colágeno e os animais com hiperadrenocorticismo apresentaram maior quantidade de colágeno na derme.

Inhibitory effect of linalool in preparations of isolated smooth muscle of rat trachea with epithelium stimulated by electromechanical coupling / Efeito inibitório do linalol em preparações isoladas de músculo liso traqueal de rato com epitélio estimulado por acoplamento eletromecânico

Plants have been used as source of therapeutic elements employed to treat several disorders, such as hypertension and asthma.The discovery of pharmacological agents that act on the contractility of airways smooth muscle can be considered to help in treating diseases of the respiratory tract. In this study, we evaluated the effect of linalool, a terpenic constituent of various aromatic and medicinal plants as an antispasmodic agent in preparations of isolated rat trachea. Linalool fully reversed the electromechanical induced contraction in isolated preparations with (188.46±13.05 μM) and without (135.21±12.76 μM) epithelium. A lower inhibitory potency was observed in phamaco mechanical contractions induced in tracheal rings with preserved epithelium (261.34±38.22 μM) or not (593.45±11.32 μM). Linalool (100 μM and 1000 μM) was Able to inhibit the curves of controlled influx for calcium and barium. In the present study, the inhibitory effect of linalool on pre-contracted rat tracheal rings was more effective in electromechanical conditions, suggesting a possible effect of this monoterpene on calcium influx through voltage-Dependent channels.

As plantas têm sido utilizadas como fonte de elementos terapêuticos empregados para tratar vários distúrbios, como hipertensão e asma. A descoberta de agentes farmacológicos que atuam sobre a contratilidade do músculo liso das vias aéreas pode ser útil no tratamento de doenças do trato respiratório. Neste estudo, avaliamos o efeito do linalol, um constituinte terpênico de várias plantas aromáticas e medicinais como agente antiespasmódico em preparações de traqueia de rato isolada. Ciência Animal26(3), 2016 O linalol reverteu completamente a contração eletromecânica induzida em preparações isoladas com (188,46±13,05 μM) e sem epitélio (135,21±12,76 μM). Observou-se uma menor potência inibitória nas contrações fármaco mecânicas induzidas em anéis traqueais com epitélio preservado (261,34±38,22 μM) ou não (593,45±11,32 μM). O linalol (100 μM e 1000 μM) foi capaz de inibir as curvas de influxo controlado para cálcio e bário. No presente estudo, o efeito inibitório do linalol em anéis traqueais de ratos pré-contraídos foi mais eficaz em condições eletromecânicas, sugerindo um possível efeito deste monoterpeno sobre o influxo de cálcio através de canais dependentes da tensão.

Inhibitory effect of linalool in preparations of isolated smooth muscle of rat trachea with epithelium stimulated by electromechanical coupling / Efeito inibitório do linalol em preparações isoladas de músculo liso traqueal de rato com epitélio estimulado por acoplamento eletromecânico

Plants have been used as source of therapeutic elements employed to treat several disorders, such as hypertension and asthma.The discovery of pharmacological agents that act on the contractility of airways smooth muscle can be considered to help in treating diseases of the respiratory tract. In this study, we evaluated the effect of linalool, a terpenic constituent of various aromatic and medicinal plants as an antispasmodic agent in preparations of isolated rat trachea. Linalool fully reversed the electromechanical induced contraction in isolated preparations with (188.46±13.05 μM) and without (135.21±12.76 μM) epithelium. A lower inhibitory potency was observed in phamaco mechanical contractions induced in tracheal rings with preserved epithelium (261.34±38.22 μM) or not (593.45±11.32 μM). Linalool (100 μM and 1000 μM) was Able to inhibit the curves of controlled influx for calcium and barium. In the present study, the inhibitory effect of linalool on pre-contracted rat tracheal rings was more effective in electromechanical conditions, suggesting a possible effect of this monoterpene on calcium influx through voltage-Dependent channels.(AU)

As plantas têm sido utilizadas como fonte de elementos terapêuticos empregados para tratar vários distúrbios, como hipertensão e asma. A descoberta de agentes farmacológicos que atuam sobre a contratilidade do músculo liso das vias aéreas pode ser útil no tratamento de doenças do trato respiratório. Neste estudo, avaliamos o efeito do linalol, um constituinte terpênico de várias plantas aromáticas e medicinais como agente antiespasmódico em preparações de traqueia de rato isolada. Ciência Animal26(3), 2016 O linalol reverteu completamente a contração eletromecânica induzida em preparações isoladas com (188,46±13,05 μM) e sem epitélio (135,21±12,76 μM). Observou-se uma menor potência inibitória nas contrações fármaco mecânicas induzidas em anéis traqueais com epitélio preservado (261,34±38,22 μM) ou não (593,45±11,32 μM). O linalol (100 μM e 1000 μM) foi capaz de inibir as curvas de influxo controlado para cálcio e bário. No presente estudo, o efeito inibitório do linalol em anéis traqueais de ratos pré-contraídos foi mais eficaz em condições eletromecânicas, sugerindo um possível efeito deste monoterpeno sobre o influxo de cálcio através de canais dependentes da tensão.(AU)

Alterações morfológicas induzidas pelo veneno da serpente PhilodryaS nattereri steindachner em ratos / Morphological changes induced by the snake venom from Philodryas nattereri Steindachner in rats

Philodryas nattererisnake is commonly distributed in arid and semiarid regions of northeast of Brazil. There is a shortage in the literature on the systemic effects of this venomin animals and humans. After 2h of intraperitoneally injection with differentdoses in rats, hemorrhagic zones in skin and the abdominal muscles were observed as well as presence of abundant erytrocytes in alveolar spaces and pulmonary congestion, hypereosinophilic cytoplasm in cells of cardiac muscle. Kidney and liver showed Histopathological changes. The snake venom of Philodryas nattereriwas capable of causing bleedind in different organs and morphological changes after poisoning.

A serpente Philodryas nattereri é comumente distribuída em regiões áridas e semi-áridas do nordeste do Brasil. Há escassez na literatura sobre os efeitos sistêmicos deste veneno em animais domésticos e humanos. Após 2h de injeção intraperitoneal com doses diferentes em ratos, foram observadas zonas hemorrágicas na pele e nos músculos abdominais, bem como a presença de eritrócitos abundantes em espaços alveolares, congestão pulmonar ecitoplasma hipereosinofílico em células do músculo estriado cardíaco. O rim e o fígado apresentaram alterações histopatológicas. O veneno da serpente Philodryas nattereri foi capaz de causar sangramento em diferentes órgãos e mudanças morfológicas após o envenenamento.

Técnica de fixação com fio metálico associado ao uso de resina acrílica, para redução de fratura no corpo da mandíbula em cão – relato de caso / Metallic wire fixation technique associated with the use of acrylic resin to reduce fracture in the jaw body in dogs – case report

As fraturas de mandíbula são bastante frequentes na clínica de pequenos animais, sendo importante para o Médico Veterinário saber diagnosticar e tratar adequadamente os pacientes que chegam ao hospital; muitas vezes, em estado crítico. O método de diagnóstico utilizado amplamente, ainda hoje, é a radiografia, por ser de baixo custo e, consequentemente, acessível para a maior parte da população, além de proporcionar diagnósticos confiáveis. A escolha do tipo de tratamento (conservativo ou cirúrgico) vai depender basicamente do tipo de fratura e de como o cirurgião vai proceder, analisando o escore de avaliação da fratura. É imprescindível, portanto, que as técnicas conservadoras e cirúrgicas, disponíveis para a realização do procedimento terapêutico, devam ser conhecidas pelo Médico Veterinário, para a correta execução durante o procedimento. O objetivo desse trabalho foi relatar um caso de redução de fratura no corpo da mandíbula de um cão, utilizando a técnica de fixação com fio metálico, associado ao uso de resina acrílica. A técnica associada, utilizada nesse trabalho, apresentou-se adequada, demonstrando resultados positivos para o tipo de paciente que estava sendo tratado, animal jovem, agitado e que a tutora não tinha tempo disponível para, regularmente, oferecer a atenção necessária aos cuidados da fratura do animal.

Mandibular fractures are quite common in small animals. Therefore, it is important for the veterinarian how to diagnose and treat, with an adequate approach, the patients that arrive at the hospital often in a critical condition, requiring a proper stabilization and then undergo with the necessary procedures to increase the chances of animal survival and reduce the possibility of sequel. Even today, the method of diagnosis widely used is the x-ray, since it is considered to have a low cost and then affordable for the majority of the people. The type of treatment (conservative or surgical) depends largely on fracture and how a surgeon wants to proceed, analyzing the factors related to the evaluation fracture score. It is imperative that the Veterinarian has total dominion over the cranial anatomy. Moreover, the surgeon has to know all the techniques available to carry out the therapeutic procedures with conservative or surgical techniques. The goal of this study was to report a case of fracture reduction in the mandibular body of a dog using the fixation technique with wire, associated with the use of acrylic resin. The associated technique used in this study can be considered as satisfactory, for showing positive results for the type of patient who was being treated, taking into account the mechanical, biological and clinical factors.

Técnica de fixação com fio metálico associado ao uso de resina acrílica, para redução de fratura no corpo da mandíbula em cão relato de caso / Metallic wire fixation technique associated with the use of acrylic resin to reduce fracture in the jaw body in dogs case report

As fraturas de mandíbula são bastante frequentes na clínica de pequenos animais, sendo importante para o Médico Veterinário saber diagnosticar e tratar adequadamente os pacientes que chegam ao hospital; muitas vezes, em estado crítico. O método de diagnóstico utilizado amplamente, ainda hoje, é a radiografia, por ser de baixo custo e, consequentemente, acessível para a maior parte da população, além de proporcionar diagnósticos confiáveis. A escolha do tipo de tratamento (conservativo ou cirúrgico) vai depender basicamente do tipo de fratura e de como o cirurgião vai proceder, analisando o escore de avaliação da fratura. É imprescindível, portanto, que as técnicas conservadoras e cirúrgicas, disponíveis para a realização do procedimento terapêutico, devam ser conhecidas pelo Médico Veterinário, para a correta execução durante o procedimento. O objetivo desse trabalho foi relatar um caso de redução de fratura no corpo da mandíbula de um cão, utilizando a técnica de fixação com fio metálico, associado ao uso de resina acrílica. A técnica associada, utilizada nesse trabalho, apresentou-se adequada, demonstrando resultados positivos para o tipo de paciente que estava sendo tratado, animal jovem, agitado e que a tutora não tinha tempo disponível para, regularmente, oferecer a atenção necessária aos cuidados da fratura do animal.(AU)

Mandibular fractures are quite common in small animals. Therefore, it is important for the veterinarian how to diagnose and treat, with an adequate approach, the patients that arrive at the hospital often in a critical condition, requiring a proper stabilization and then undergo with the necessary procedures to increase the chances of animal survival and reduce the possibility of sequel. Even today, the method of diagnosis widely used is the x-ray, since it is considered to have a low cost and then affordable for the majority of the people. The type of treatment (conservative or surgical) depends largely on fracture and how a surgeon wants to proceed, analyzing the factors related to the evaluation fracture score. It is imperative that the Veterinarian has total dominion over the cranial anatomy. Moreover, the surgeon has to know all the techniques available to carry out the therapeutic procedures with conservative or surgical techniques. The goal of this study was to report a case of fracture reduction in the mandibular body of a dog using the fixation technique with wire, associated with the use of acrylic resin. The associated technique used in this study can be considered as satisfactory, for showing positive results for the type of patient who was being treated, taking into account the mechanical, biological and clinical factors.(AU)

Alterações morfológicas induzidas pelo veneno da serpente PhilodryaS nattereri steindachner em ratos / Morphological changes induced by the snake venom from Philodryas nattereri Steindachner in rats

Philodryas nattererisnake is commonly distributed in arid and semiarid regions of northeast of Brazil. There is a shortage in the literature on the systemic effects of this venomin animals and humans. After 2h of intraperitoneally injection with differentdoses in rats, hemorrhagic zones in skin and the abdominal muscles were observed as well as presence of abundant erytrocytes in alveolar spaces and pulmonary congestion, hypereosinophilic cytoplasm in cells of cardiac muscle. Kidney and liver showed Histopathological changes. The snake venom of Philodryas nattereriwas capable of causing bleedind in different organs and morphological changes after poisoning.(AU)

A serpente Philodryas nattereri é comumente distribuída em regiões áridas e semi-áridas do nordeste do Brasil. Há escassez na literatura sobre os efeitos sistêmicos deste veneno em animais domésticos e humanos. Após 2h de injeção intraperitoneal com doses diferentes em ratos, foram observadas zonas hemorrágicas na pele e nos músculos abdominais, bem como a presença de eritrócitos abundantes em espaços alveolares, congestão pulmonar ecitoplasma hipereosinofílico em células do músculo estriado cardíaco. O rim e o fígado apresentaram alterações histopatológicas. O veneno da serpente Philodryas nattereri foi capaz de causar sangramento em diferentes órgãos e mudanças morfológicas após o envenenamento.(AU)

Alterações morfológicas de pele de camundongos inoculados com o veneno total da serpente Philodryas nattereri / Morphological alterations in mice skins inoculated with the total snake venom of Philodryas nattereri / Las alteraciones morfológicas en la piel de ratones causadas por el veneno de la serpiente Philodryas nattereri

Venenos de serpentes são compostos por substâncias ativas complexas, sendo a maioria delas de natureza proteica, causando diversos efeitos no ser humano e animais domésticos podendo levar ao óbito. Philodryas nattereri é uma serpente nativa da região do Ceará, sendo encontrada em todo o estado. Esse estudo teve por objetivo conhecer as alterações morfofisiológicas de pele de camundongos após inoculação com o veneno total desta serpente. Os animais foram distribuídos em dois grupos que receberam concentrações de 40µg/mL e 20 µg/mL respectivamente, inoculados via subcutânea, além de um terceiro grupo que recebeu via intradérmica 40µg/mL do veneno. Os resultados macroscópicos apresentaram a presença de uma crosta na região inoculada, bem como a presença de hemorragia, tal atividade foi confirmada por achado histopatológico. Microscopicamente, todos os grupos experimentais apresentaram infiltrado inflamatório linfoblástico e de polimorfonucleares, hemorragia, edema, e presença de fibrose. O veneno da serpente Philodryas nattereri alterou a arquitetura normal do tegumento. Nossos resultados corroboraram em demonstrar tais alterações, uma vez que esta substância tóxica de origem animal, presente na nossa biodiversidade nordestina apresenta poucos dados na literatura, sendo desta forma, uma importante ferramenta para estudos das alterações morfofisiológicas de pele.(AU)

Snake venoms are composed of complex active substances, most of them of protein nature, causing various effects on humans and domestic animals and can lead to death. Philodryas nattereri is a native snake Ceara region, found throughout the state. This study aimed to know the morphological and physiological changes in mouse skin after inoculation with the total venom this serpente. The animals were divided into two groups that received concentrations of 40µg/mL and 20µg/mL respectively, inoculated subcutaneously, and a third group that received intradermal 40µg/mL of the venom. The macroscopic results showed the presence of a crust in the inoculated area, and the presence of bleeding, this activity was confirmed by histopathological analysis. Microscopically, all experimental groups had lymphoblastic and polymorphonuclear inflammatory infiltration, hemorrhage, edema, and fibrosis. The venom of the snake Philodryas nattereri altered the normal integument architecture. Our results corroborate to demonstrate such changes, since this toxic substance of animal origin present in our Northeast biodiversity presents few literature data, thereby being an important tool for the study of morphological and physiological changes in the skin.(AU)

Los venenos de serpientes se componen de sustancias activas complejas, la mayoría de ellos de naturaleza proteica, provocando diversos efectos sobre los seres humanos y en los animales domésticos pueden llevar a la muerte. Philodryas nattereri es una serpiente nativa de la región de Ceará, que se encuentra en todo el estado. Este estudio tuvo como objetivo conocer los cambios morfológicos y fisiológicos en la piel de ratones después de la inoculación con todo el veneno de esta serpiente. Los animales fueron divididos en dos grupos que recibieron las concentraciones de 40µg/mL y 20µg /mL, respectivamente, por vía subcutánea inoculado, y un tercer grupo recibieron intradérmica 40µg/mL veneno. Los resultados macroscópicos mostraron la presencia de una costra en el área inoculada, y la presencia de sangrado, esta actividad se confirmó por análisis histopatológica. Microscópicamente, todos los grupos experimentales tuvieron infiltración linfoblástica y polimorfonucleares inflamatoria, hemorragia, edema y fibrosis. El veneno de la serpiente Philodryas nattereri altera la arquitectura normal del tegumento. Nuestros resultados corroboran para demostrar tales cambios, ya que esta sustancia tóxica de origen animal presente en nuestra biodiversidad Northeast presenta pocos datos de la literatura, siendo por lo tanto una herramienta importante para el estudio de los cambios morfológicos y fisiológicos en la piel.(AU)

Alterações morfológicas de pele de camundongos inoculados com o veneno total da serpente Philodryas nattereri / Morphological alterations in mice skins inoculated with the total snake venom of Philodryas nattereri / Las alteraciones morfológicas en la piel de ratones causadas por el veneno de la serpiente Philodryas nattereri

Venenos de serpentes são compostos por substâncias ativas complexas, sendo a maioria delas de natureza proteica, causando diversos efeitos no ser humano e animais domésticos podendo levar ao óbito. Philodryas nattereri é uma serpente nativa da região do Ceará, sendo encontrada em todo o estado. Esse estudo teve por objetivo conhecer as alterações morfofisiológicas de pele de camundongos após inoculação com o veneno total desta serpente. Os animais foram distribuídos em dois grupos que receberam concentrações de 40µg/mL e 20 µg/mL respectivamente, inoculados via subcutânea, além de um terceiro grupo que recebeu via intradérmica 40µg/mL do veneno. Os resultados macroscópicos apresentaram a presença de uma crosta na região inoculada, bem como a presença de hemorragia, tal atividade foi confirmada por achado histopatológico. Microscopicamente, todos os grupos experimentais apresentaram infiltrado inflamatório linfoblástico e de polimorfonucleares, hemorragia, edema, e presença de fibrose. O veneno da serpente Philodryas nattereri alterou a arquitetura normal do tegumento. Nossos resultados corroboraram em demonstrar tais alterações, uma vez que esta substância tóxica de origem animal, presente na nossa biodiversidade nordestina apresenta poucos dados na literatura, sendo desta forma, uma importante ferramenta para estudos das alterações morfofisiológicas de pele.

Snake venoms are composed of complex active substances, most of them of protein nature, causing various effects on humans and domestic animals and can lead to death. Philodryas nattereri is a native snake Ceara region, found throughout the state. This study aimed to know the morphological and physiological changes in mouse skin after inoculation with the total venom this serpente. The animals were divided into two groups that received concentrations of 40µg/mL and 20µg/mL respectively, inoculated subcutaneously, and a third group that received intradermal 40µg/mL of the venom. The macroscopic results showed the presence of a crust in the inoculated area, and the presence of bleeding, this activity was confirmed by histopathological analysis. Microscopically, all experimental groups had lymphoblastic and polymorphonuclear inflammatory infiltration, hemorrhage, edema, and fibrosis. The venom of the snake Philodryas nattereri altered the normal integument architecture. Our results corroborate to demonstrate such changes, since this toxic substance of animal origin present in our Northeast biodiversity presents few literature data, thereby being an important tool for the study of morphological and physiological changes in the skin.

Los venenos de serpientes se componen de sustancias activas complejas, la mayoría de ellos de naturaleza proteica, provocando diversos efectos sobre los seres humanos y en los animales domésticos pueden llevar a la muerte. Philodryas nattereri es una serpiente nativa de la región de Ceará, que se encuentra en todo el estado. Este estudio tuvo como objetivo conocer los cambios morfológicos y fisiológicos en la piel de ratones después de la inoculación con todo el veneno de esta serpiente. Los animales fueron divididos en dos grupos que recibieron las concentraciones de 40µg/mL y 20µg /mL, respectivamente, por vía subcutánea inoculado, y un tercer grupo recibieron intradérmica 40µg/mL veneno. Los resultados macroscópicos mostraron la presencia de una costra en el área inoculada, y la presencia de sangrado, esta actividad se confirmó por análisis histopatológica. Microscópicamente, todos los grupos experimentales tuvieron infiltración linfoblástica y polimorfonucleares inflamatoria, hemorragia, edema y fibrosis. El veneno de la serpiente Philodryas nattereri altera la arquitectura normal del tegumento. Nuestros resultados corroboran para demostrar tales cambios, ya que esta sustancia tóxica de origen animal presente en nuestra biodiversidad Northeast presenta pocos datos de la literatura, siendo por lo tanto una herramienta importante para el estudio de los cambios morfológicos y fisiológicos en la piel.

Toxicidad del veneno de Crotalus durissus cascavella en células de mamíferos / Crotalus durissus cascavella venom toxicity to mammalian cells / Toxicidade do veneno de Crotalus durissus cascavella em células de mamíferos

Las serpientes del género Crotalus ganaron espacio significativo en el campo científico desde el desarrollo de investigaciones con su veneno que involucran la actividad citotóxica. Crotalus durissus cascavella es la única subespecie grabadas del bioma de la Caatinga del nordeste de Brasil y los estudios carecen en sus propiedades del veneno. El presente estudio evaluó el veneno crudo de C. d. cascavella por su actividad citotóxica in vitro contra líneas celulares tumorales y las células normales. El mecanismo de la muerte celular inducida por este veneno también se investigó. C. d. cascavella mostró una alta citotoxicidad (valores de IC50 que oscila desde 2,7 hasta 6,9 g/mL) contra cinco líneas de células tumorales, entre las cuales: OVCAR - 8 y SKOV3 (carcinoma de ovario), PC-3M (carcinoma metastásico de próstata), MCF-7 (carcinoma de mama), SF - 268 (glioblastoma) y PBMC también. Las células tratadas con C. d. cascavella disparó la cascada apoptótica, según lo confirmado por diversos métodos que se muestran en este trabajo. Estos resultados refuerzan así el potencial biomédico y farmacológico de las toxinas del veneno de esta especie.

Snakes from the genus Crotalus gained significant space in the scientific field since the development of researches with their venom involving cytotoxic activity. Crotalus durissus cascavella is the only subspecies recorded of the Caatinga biome of Northeastern Brazil and its noticed a lack of studies on its venom properties. The present study evaluated the crude venom of C. d. cascavella for its cytotoxic activity in vitro against both tumor cell lines and normal cells. The mechanism of cell death induced by this venom was also investigated. C. d. cascavella venom presented high cytotoxicity (IC50 values ranging from 2.7 to 6.9 µg/mL) against five tumor cells lines: OVCAR-8 and SKOV3 (ovarian carcinomas), PC-3M (metastatic prostate carcinoma), MCF-7 (breast carcinoma), and SF-268 (glioblastoma) and PBMC as well. The cells treated with C. d. cascavella venom triggered the apoptotic pathway as confirmed by several methods. These results underline the biomedical potential of toxins from the venom from this species.

Serpentes do Gênero Crotalus ganhou espaço significativo no campo científico, desde o desenvolvimento de pesquisas com seu veneno envolvendo atividade citotóxica. A Crotalus durissus cascavella (C.d.cascavella) é uma subespécie característica da Caatinga do Nordeste do Brasil e faltam estudos sobre as propriedades de seu veneno. O presente estudo avaliou o veneno bruto de C. d. cascavella para a sua atividade citotóxica in vitro contra as linhagens de células tumorais e células normais. O mecanismo de morte celular induzida por este veneno também foi investigado. Observou-se alta citotoxicidade (valores de IC50 entre 2,7-6,9 µg/mL) contra cinco linhagens de células tumorais, dentre elas: OVCAR - 8 e SKOV3 (carcinoma ovariano), PC-3M (carcinoma metastático de próstata), MCF-7 (carcinoma mamário), SF - 268 (glioblastoma) e PBMC. As células tratadas dispararam a cascata apoptótica, como confirmado por vários métodos demonstrados neste trabalho. Esses resultados reforçam, assim, o potencial biomédico e farmacológico das toxinas do veneno dessa espécie.