Taiwan cobra envenoming: serum venom concentration before and after specific treatment and relationship with debridement of necrotic wound tissue

Background: Bivalent freeze-dried neurotoxic (FN) antivenom has been the primary treatment since the 1980s for Taiwan cobra (Naja atra) envenomation in Taiwan. However, envenomation-related wound necrosis is a significant problem after cobra snakebites. In the present study, we analyzed the changes in serum venom concentration before and after antivenom administration to discover their clinical implications and the surgical treatment options for wound necrosis. Methods: The patients were divided into limb swelling and wound necrosis groups. The clinical outcome was that swelling started to subside 12 hours after antivenom treatment in the first group. Serum venom concentrations before and after using antivenoms were measured to assess the antivenom's ability to neutralize the circulating cobra venom. The venom levels in wound wet dressing gauzes, blister fluids, and debrided tissues were also investigated to determine their clinical significance. We also observed the evolutional changes of wound necrosis and chose a better wound debridement timing. Results: We prospectively enrolled 15 Taiwan cobra snakebite patients. Males accounted for most of this study population (n = 11, 73%). The wound necrosis group received more antivenom doses than the limb swelling group (4; IQR:2-6 vs 1; IQR:1-2, p = 0.05), and less records of serum venom concentrations changed before/after antivenom use (p = 0.0079). The necrotic wound site may release venom into circulation and cause more severe envenomation symptoms. Antivenom can efficiently diminish limb swelling in cobra bite patients. However, antivenom cannot reduce wound necrosis. Patients with early debridement of wound necrosis had a better limb outcome, while late or without debridement may have long-term hospital stay and distal limb morbidity. Conclusions: Antivenom can efficiently eliminate the circulating cobra venom in limb swelling patients without wound necrosis. Early debridement of the bite site wound and wet dressing management are suggestions for preventing extended tissue necrosis and hospital stay.(AU)

Spontaneous osteoarthritis in dogs - clinical effects of single and multiple intra-articular injections of hyaluronic acid

Background: The treatments of osteoarthritis (OA) are commonly conservative and multimodal to relieve pain and improve movement. Intra-articular injection of hyaluronic acid (IAHA) has been studied as a treatment option for OA in dogs. IAHA helps restore the viscoelasticity of the synovial fluid and relieves the clinical symptoms of OA. However, the efficacy of IAHA in dogs is still a controversial subject. This study aims to confirm the IAHA effect in dogs with spontaneous OA and to compare the effectiveness depending on the number of injections. Materials, Methods & Results: Thirty dogs with spontaneous OA were assigned to a single injection group (n=17) and a 3-weekly injections group (n=13). Dogs weighing less than 10 kg were injected 1 mL of HA to the OA joint, and more than 10 kg dogs were injected 2 mL of HA. In the case of the 3-weekly injections group, the same amount was administered 3 times at 1-week intervals. After the injection, physical and orthopedic examinations were performed to check for complications. Radiographic OA score was evaluated before and 3 months after the injection to confirm and to evaluate the progression of OA. Clinical symptom evaluations were performed on pre-injection, 1-, 2-, and 3-months post-injection. They consisted of the clinical lameness score by veterinarians and Canine Brief Pain Inventory (CBPI) by owners. Results were compared with unpaired t-test, repeated-measures ANOVA with Tukey's or Sidak's multiple comparison test, or Wilcoxon test, with P < 0.05. Patients had a median age of 9 years (range 3 to 16 years) and a bodyweight of 4.8 kg (range 2 to 48 kg). No systemic side effects or major complications were detected during the trial period. IAHA produced temporary pain and discomfort in 6 cases. There was no change in the radiographic OA score before and 3 months after injections in both groups, and the difference between groups was not confirmed. In both groups, the clinical lameness score significantly decreased at 1, 2, 3 months after injection compared with pre-injection. The score was lower at 3 months after the injection than at 1 month. The clinical lameness score had no significant difference between the groups. Similarly, CBPI was all decreased in the single injection group and 3-weekly injections group compared to pre-injection, and the score at 3 months post-injection was lower than at 1 month. No significant differences between the groups were found in CBPI. Discussion: Most studies on the efficacy of IAHA in canine OA have been conducted using an experimental model, so studies on spontaneous canine OA are insufficient. This study confirmed that IAHA improves clinical symptoms such as pain relief and movement improvement in spontaneous OA dogs using CBPI and clinical lameness score. In order to confirm the optimal IAHA protocol, a single IAHA and 3-weekly IAHA were compared. The result shows that clinical symptoms improved in both single and 3-weekly injections groups, but no significant difference was confirmed during the 3-month study period. These findings may suggest that a single IAHA may have a similar effect to multiple IAHA, and repeated injections are unnecessary. In humans and canine OA models, it is reported that the effect of IAHA was maintained for 6 months. This study showed that the effect of IAHA was maintained for 3 months study period and that clinical symptoms improved at 3 months than at 1 month. In conclusion, these findings suggested that IAHA improves clinical symptoms in dogs with spontaneous OA, and a single IAHA showed a similar effect to 3 weekly IAHA.

Úlcera de córnea em bugio-ruivo (Alouatta guariba clamitans) - tratamento com soro heterólogo / Corneal ulcer in a Southern brown howler monkey (Alouatta guariba clamitans) - treatment with heterologous serum

Background: In the routine care of non-human primates, ocular trauma is frequent, however, unlike the small animal clinic, the prevalence of corneal ulcers is not documented. Among the numerous therapeutic options available in dogs, blood serum is being increasingly used as an adjuvant treatment in these conditions, due to its tear-like properties. Based on this, the present study aims to describe a case of corneal ulcer in a southern brown howler monkey (Alouatta guariba clamitans) attacked by a porcupine, and the use of heterologous serum obtained from an equine as an adjuvant treatment. Case: A southern brown howler monkey (Alouatta guariba clamitans), which had been attacked by porcupine quills, was treated at a University Veterinary Hospital. During the clinical examination, the presence of blepharospasm and secretion in the right eye was noticed. The ophthalmological examination, through the fluorescein test, detected the presence of an extensive superficial corneal ulcer in the right eye. After removing the spines, the corneal ulcer was treated with tobramycin-based eye drops, 1% atropine sulfate eye drops, and serum from equine blood in the form of eye drops, as an adjuvant therapy. After 5 days of treatment, the fluorescein test was repeated, which was negative in both eyes due to complete healing of the lesion, and thus the treatment was concluded. Discussion: The scarcity of scientific literature on wild animals is one of the factors responsible for the difficulty in advancing clinical and surgical procedures in non-human primates. Corneal ulcers are characterized by the loss of corneal epithelium with exposure of the stroma. The main clinical treatments adopted include antimicrobial therapy, analgesics, lubricating agents, and antiprotease drugs. Widely used as an adjuvant therapy in corneal ulcers in small animals, blood serum presents some advantages, as it is rich in growth factors, vitamins, immunoglobulins, and anti-collagenolytic substances, in addition to being obtained for a low cost. Considering the aforementioned, in the case reported, it was decided to use blood serum obtained from an equine as an adjuvant treatment of the corneal ulcer in a southern brown howler monkey. Complete healing of the corneal ulcer was confirmed in just five days, contributing to the well-being of this animal and contributing to the evolution of ophthalmology in this species that is still poorly studied.

Effectiveness of oral electrolyte solutions with different compositions for the treatment of neonatal calves with induced osmotic diarrhea / Eficácia de soluções eletrolíticas orais com diferentes composições no tratamento de bezerros neonatos com diarreia osmótica induzida

In a randomized controlled trial, we evaluated the effects of five oral electrolyte solutions (OESS) with different compositions of water, electrolyte, and acid-base balances of diarrheal neonatal calves. Osmotic diarrhea and dehydration were induced with sucrose in milk, spironolactone, and hydrochlorothiazide for 48 h in thirty 10-day old Holstein healthy calves with 43.5 ± 3.80 kg BW who were fed with natural milk. They were allocated to five treatment groups (n=6) based on the administered OES (commercial: OES A, B, C, D; and non-commercial: OES UEL). On the day of treatment, the calves received 6L of OES in two doses apart from milk intakes. Venous blood samples were collected at -48h (start of induction), -24h, Oh (start of the treatment day), 8h, 16h, 24h, 48h, and 72h. TPP, glucose, D-lactate, L-lactate, pH, pCO2, HCO3, BE, Na, K, CI, SID3, SIG, AG, Atot and percentage change in plasma volume (%PV) were measured or calculated and analyzed by two-way repeated measures ANOVA. All the calves developed osmotic diarrhea, mild to moderate dehydration, hyponatremia, relative hyperchloremia, and moderate to severe metabolic acidosis. The tested OESS were well accepted by the calves and effective in reversing dehydration, electrolyte imbalances, and metabolic acidosis. OES D did not completely correct hyponatremia, and SEO B caused transient hyperglycemia. It has been concluded that all the tested OESS are safe and effective for the treatment of diarrhea in calves with moderate degrees of dehydration and metabolic acidosis, which indicates that they have proper compositions for this purpose.

Em um ensaio clínico controlado e aleatório, foram comparados os efeitos de cinco soluções eletrolíticas orais (SEOs) sobre os equilíbrios hídrico, eletrolítico e ácido-base de bezerros neonatos diarreicos. Diarreia osmótica e desidratação foram induzidas com sacarose no leite, espironolactona e hidroclorotiazida, por 48h, em 30 bezerros Holandeses com 10 dias de idade, 43,5 ± 3,8kg de peso, e alimentados com leite natural. Eles foram distribuídos em cinco grupos de tratamento (n=6) de acordo com a SEO administrada (comercial: SEO A, B, C, D; e não comercial: SEO UEL). No dia do tratamento, os bezerros receberam 6L de SEO em duas doses além da ingestão de leite. Amostras de sangue venoso foram coletadas em -48h (início da indução), - 24h, Oh (início do dia de tratamento), 8h, 16h, 24h, 48h e 72h. PPT, glicose, lactatos Le D, pH, pCO2, HCO3, BE, Na, K, CI, SID3, SIG, AG, Atot e variação percentual no volume plasmático (%VP) foram mensurados ou calculados, e analisados por meio de ANOVA de duas vias de medidas repetidas. Todos os bezerros desenvolveram diarreia osmótica, desidratação leve a moderada, hiponatremia, hipercloremia relativa e acidose metabólica moderada a grave. As SEOs testadas foram bem aceitas pelos bezerros e eficazes para a reversão da desidratação, dos desequilíbrios eletrolíticos e da acidose metabólica. A SEO D não corrigiu completamente a hiponatremia, e a SEO B causou hiperglicemia transitória. Conclui-se que todas as SEOs são eficazes para o tratamento da diarreia em bezerros com graus moderados de desidratação e de acidose metabólica, o que indica que possuem composições adequadas para esse fim.

Inhibition potential of Caryocar brasiliense on methicillin-resistant Staphylococcus pseudintermedius isolated from the ocular surface of dogs with ophthalmopathies / Potencial de inibição do Caryocar brasiliense sobre Staphylococcus pseudintermedius resistente à meticilina isolado da superfície ocular de cães com oftalmopatias

The indiscriminate use of antibiotics has contributed to the emergence of multiresistant bacteria. Faced with this, the search for antibiotics from plants has proven to be a promising alternative. The objective of this work was to isolate and identify Staphylococcus sp. resistant to methicillin of the ocular surface of dogs with ophthalmopathies and to evaluate its susceptibility to alcoholic extract of the bark and hexane extract of the pulp of Caryocar brasiliense. Biological material was collected from the ocular surface of 21 dogs presenting ophthalmopathies. We isolated 64 S. pseudintermedius, among these, 4 isolates were identified as methicillin-resistant S. pseudintermedius (MRSP). The alcoholic extract of C. brasiliense peel was able to inhibit the bacterial growth of MRSP isolates at a concentration of 2.2%. Thus, the extract from the C. brasiliense peel has antimicrobial potential and represents an alternative in the control of MRSP.

O uso indiscriminado de antibióticos tem contribuído para o surgimento de bactérias multirresistentes. Diante disso, a busca por antibióticos a partir de plantas tem se mostrado uma alternativa promissora. O objetivo deste trabalho foi isolar e identificar Staphylococcus sp. resistente à meticilina da superfície ocular de cães com oftalmopatias e avaliar sua susceptibilidade ao extrato alcoólico da casca e ao extrato hexânico da polpa de Caryocar brasiliense. O material biológico foi coletado da superficie ocular de 21 cães com oftalmopatia. Isolaram-se 64 S. pseudintermedius; entre esses, quatro isolados foram identificados como S. pseudintermedius resistente à meticilina (MRSP). O extrato alcoólico da casca de C. brasiliense foi capaz de inibir o crescimento bacteriano dos isolados de MRSP na concentração de 2,2%. Dessa forma, o extrato da casca de C. brasiliense possui potencial antimicrobiano e representa uma alternativa no controle de MRSP.

Effects of supplementation with vitamins C and E on the acute inflammatory response in Piaractus mesopotamicus / Efeitos da suplementação com vitaminas C e E na resposta inflamatória aguda em Piaractus mesopotamicus

Vitamins C and E are potent antioxidants that reduces the harmful effects of stress in several species including fish. In this study, it was evaluated the effect of vitamins C, E and their combination in the acute aerocystitis induced by inactivated Aeromonas hydrophila in pacu. 288 fish were distributed into 4 groups supplemented for 90 days: G1-control; G2- supplemented with 500 mg of Vitamin C; G3-supplemented with 500 mg of Vitamin E; G4-supplemented with 500 mg of Vitamin C + 500 mg of Vitamin E. The fish were divided in three groups, the first was not inoculated; second were inoculated in the swim bladder with 3 x 109 CFU of inactivated A. hydrophila and the last one with saline. The inflammatory exudate was collected from the swim bladder for assessment of cellular component and cytochemistry. The results showed higher accumulation of leukocytes in fish inoculated with bacteria. Cytochemistry was effective identifying thrombocytes, lymphocytes, macrophages and, granulocytes present in the exudate. It was also observed fish that received supplementation with vitamins presented higher accumulation of total cells in the exudate with a predominance of lymphocytes and thrombocytes. These results suggested that supplementation with vitamins improved the immunological responses.

As vitaminas C e E são potentes antioxidantes que reduzem os efeitos nocivos do estresse em várias espécies, incluindo peixes. Neste estudo, avaliou-se o efeito das vitaminas C, E e sua combinação na aerocistite aguda induzida por Aeromonas hydrophila inativada em pacu. 288 peixes foram distribuídos em 4 grupos suplementados por 90 dias: G1-controle; G2- suplementado com 500 mg de Vitamina C; G3-suplementado com 500 mg de Vitamina E; G4-suplementado com 500 mg de Vitamina C + 500 mg de Vitamina E. Os peixes foram divididos em três grupos, o primeiro não foi inoculado; o segundo foi inoculado na bexiga natatória com 3 x 109 UFC de A. hydrophila inativada e a última com soro fisiológico. O exsudato inflamatório foi coletado da bexiga natatória para avaliação do componente celular e citoquímica. Os resultados mostraram maior acúmulo de leucócitos nos peixes inoculados com a bactéria. A citoquímica foi eficaz na identificação de trombócitos, linfócitos, macrófagos e granulócitos presentes no exsudato. Também foi observado que os peixes que receberam suplementação com vitaminas apresentaram maior acúmulo de células totais no exsudato com predominância de linfócitos e trombócitos. Esses resultados sugeriram que a suplementação com vitaminas melhorou as respostas imunológicas.

Evaluation of the acid-neutralizing and cytotoxicity properties of novel plant mucilage used as an alternative treatment for peptic ulcers and as antacids in Namibia

Hypersecretion of gastric acid damages the stomach lining, causing the formation of peptic ulcers. Mucilage from medicinal plants offers a relaxing and soothing effect to the endodermal lining of the gut and has antacid properties, which can protect the mucosal lining from gastric acidity. This is the first report aimed to evaluate the physicochemical characteristics, acid-neutralizing, and cytotoxicity properties of traditionally used aqueous mucilage from Asparagus exuvialis and Sesamum capense. The physicochemical properties were determined by biochemical methods. Acid neutralizing and buffering capacities were determined by titration methods. Normal mouse embryonic fibroblast cells were used for cytotoxicity evaluation by MTT assay. The physicochemical characterization confirmed the presence of carbohydrates, alkaloids, saponins, proteins, tannins, flavonoids, and glycosides. Sesamum capense mucilage exhibited the most potent artificial gastric juice neutralizing capacity pH of 4.62±0.01, 8.0±0.00 acid neutralization capacity per gram of acid, and 30 minutes duration of acid neutralization. The aqueous mucilage from S. capense did not cause any significant cytotoxicity to 3T3 cell lines showing an IC50 value of 91.5 ± 0.06 µg mL-1, confirming the safe nature of the mucilage. These findings revealed that S. capense has the potential to neutralize gastric acid responsible for ulceration and can be safely consumed.(AU)

Análise da atividade antibacteriana do extrato aquoso de Curcuma longa L. e digluconato de clorexidina no tratamento de doenças periodontais em cães e gatos / Analysis of the antibacterial activity of the aqueous extract of Curcuma longa L. in the treatment of periodontal diseases in dogs and cats / Análisis de la actividad antibacteriana del extracto acuoso de Curcuma longa L. en el tratamiento de enfermedades periodontales en perros y gatos

A doença periodontal é a afecção mais comum em cães e gatos. Atualmente, a substância mais eficaz para realizar a limpeza oral em animais de companhia é a Clorexidina muito eficiente no controle das placas bacterianas, mas seu uso prolongado causa muitos efeitos colaterais. O uso de plantas medicinais vem ganhando espaço na veterinária. Curcuma longa L., por exemplo, apresenta grande potencial terapêutico. A cúrcuma despertou interesse no campo da periodontia, pois atinge tanto as bactérias, com sua ação antimicrobiana, como as células inflamatórias do hospedeiro por sua ação anti-inflamatória. Buscando uma alternativa com menos efeito colateral, o presente estudo teve como objetivo avaliar a ação antibacteriana de Curcuma longa L. e do digluconato de clorexidina sobre alguns micro-organismos causadores dessa doença. O extrato seco de Curcuma longa L. e o digluconato de clorexidina foram adquiridos comercialmente de uma farmácia de manipulação, onde, posteriormente, obteve-se os extratos aquosos nas concentrações 1%; 2,5%; 5%; 10% e 20% e solução de clorexidina 2%. Realizou-se o preparo do inóculo, na escala de 0,5 de MacFarland, das cepas de E. coli e S. aureus. Todas as concentrações foram testadas em triplicata. Utilizou-se digluconato de clorexidina 2% como controle positivo e solução de água destilada com polissorbato 20 como controle negativo. Staphylococcus aureus mostrou-se sensível ao extrato aquoso de Curcuma longa L. em contrapartida Escherichia coli apresentou resistência. Por este estudo ter como objetivo o tratamento de doenças periodontais, não descarta-se a eficácia do extrato aquoso de curcuma longa sobre a bactéria Gram positiva que está presente na fase inicial dessa doença em cães e gatos, já que demonstrou sensibilidade, tornando necessário novas pesquisas para corroborar este estudo.

Periodontal disease is the most common condition in dogs and cats. Currently, the most effective substance in the control of bacterial plaques to carry out oral cleaning in pets is Chlorhexidine, but its prolonged use causes many side effects. As an alternative, the use of medicinal plants has been gaining ground in veterinary medicine, Curcuma longa L., for example, has great therapeutic potential. Curcumin has aroused interest in the field of periodontics due to its antimicrobial and anti-inflammatory action. Seeking an alternative with fewer or no side effects, the present study aimed to evaluate the antibacterial action of Curcuma longa L. on some microorganisms that cause this disease. The dry extract of turmeric and the chlorhexidine digluconate were purchased commercially from a compounding pharmacy, where, subsequently, the aqueous extracts were obtained in concentrations of 1%; 2.5%; 5%; 10% and 20% and 2% chlorhexidine solution. The inoculum was prepared, on a MacFarland scale of 0.5, for the strains of E. coli and S. aureus. All concentrations were tested in triplicate. 2% chlorhexidine digluconate was used as a positive control and a solution of distilled water with polysorbate 20 as a negative control. Staphylococcus aureus was sensitive to the aqueous extract of Curcuma longa, while Escherichia coli showed resistance. Because this study aims to prevent periodontal diseases, the effectiveness of the aqueous extract of curcuma longa on the Gram positive bacteria that is present in the initial phase of this disease in dogs and cats it demonstrate sensitivity, and further research is necessary to corroborate this study.

La enfermedad periodontal es la condición más común en perros y gatos. Actualmente, la sustancia más eficazes en el control de las placas bacterianas para realizar la limpieza bucal en las mascotas es la Clorhexidina, pero su uso prolongado provoca muchos efectos secundarios. Como alternativa, en la medicina veterinaria ha ido ganando terreno el uso de plantas medicinales, por ejemplo, la Curcuma longa L. tiene un gran potencial terapéutico. La curcumina ha despertado interés en el campo de la periodoncia debido a su acción antimicrobiana y antiinflamatoria. Buscando una alternativa con menos o ningún efecto secundario, el presente estudio tuvo como objetivo evaluar la acción antibacteriana de Curcuma longa L. sobre algunos microorganismos que causan esta enfermedad. El extracto seco de Curcuma longa L. y el digluconato de clorhexidina fueron adquiridos comercialmente en una farmacia de compuestos, donde posteriormente se obtuvieron los extractos acuosos a concentraciones del 1%; 2,5%; 5%; al 10% y al 20% Solución de clorhexidina y al 2%. El inóculo se preparó, en una escala de MacFarland de 0,5, para las cepas de Escherichia coli y Staphylococcus aureus. Todas las concentraciones se ensayaron por triplicado. Se utilizó digluconato de clorhexidina al 2% como control positivo y como control negativo una solución de agua destilada con polisorbato 20. Staphylococcus aureus fue sensible al extracto acuoso de Curcuma longa, mientras que Escherichia coli mostró resistencia. Debido a que este estudio tiene como objetivo prevenir las enfermedades periodontales, no se puede descartar la efectividad del extracto acuoso de Curcuma longa sobre la bacteria Gram positiva que está presente en la fase inicial de esta enfermedad en perros y gatos, ya que demostró sensibilidad, lo que hace que se realicen más investigaciones necesario para corroborar este estúdio.

Carcinoma de células escamosas corneal em um cão - uso da Mitomicina C 0, 02% como adjuvante no tratamento / Corneal squamous cell carcinoma in a dog - use of Mitomycin C 0. 02% as an adjuvant therapy

Background: Although Squamous Cell Carcinoma (SCC) is most commonly seen in the epidermis, this malignant neoplasm can manifest in various other tissues. A wide range of factors may be related to the development of SCC in the cornea, with continuous exposure to ultraviolet radiation and chronic friction to the ocular surface being the most accepted theories. In addition to surgical procedures, the use of mitomycin C in the topical treatment of corneal SCC has shown good results in therapeutic management. Thus, the objective of the current work is to report the satisfactory response observed in the use of mitomycin C in a case of SCC in the cornea of a dog. Case: A 9-year-old male Pug dog was attended by the Veterinary Ophthalmology and Microsurgery Sector (SOMVET) of the University Veterinary Hospital (HVU) of the Federal University of Santa Maria (UFSM) with Squamous Cell Carcinoma (SCC) in the cornea of the left eye, which had recurred after a previous surgical intervention. Secretion and discomfort in the left eye were noted during clinical examination. In addition, both eyes presented pigmentary keratitis in the medial corner. Surgical excision of the neoplasm was performed using the surgical technique of anterior lamellar keratectomy. In the immediate postoperative period, topical therapy was started with eye drops based on mitomycin C at 0.02%, for a period of 28 consecutive days. The use of this chemotherapy drug in the topical form was intended to minimize the chances of recurrence of the clinical condition, since the patient is predisposed to this alteration. In addition, supportive therapy was implemented to improve patient comfort, consisting of the use of tobramycin-based eye drops (6 times a day, for 14 days), atropine 1% eye drops (BID, for 3 days), lubricating eye drops based on sodium hyaluronate (3 times a day, for continuous use), and immunomodulatory eye drops based on tacrolimus 0.02% (twice a day, for continuous use). The patient was evaluated 7, 14, 21, and 28 days after surgery, when good results were observed. One year after treatment, the dog was still showing no signs of recurrence of the treated clinical condition. Discussion: It is known that chronic friction on the surface of the cornea predisposes to the diagnosis of corneal SCC. Accordingly, in the clinical examination of the patient in this report, the presence of bilateral pigmentary keratitis was observed, an alteration that leads to a framework of chronic aggression to the cornea. Surgical treatment is recommended to remove the tumor mass in the ocular region. However, in cases of corneal SCC, the literature highlights that recurrence after surgical excision is a common factor. As the patient in this study arrived at the clinic with a history of recurrence, topical therapy with mitomycin C associated with surgical treatment was instituted. This chemotherapy drug has shown encouraging results in the treatment of some neoplasms, especially SCC. Its use in this case supported previous findings, pointing to a satisfactory result in which the patient had no recurrences after one year of follow-up. In addition, the concentration and frequency used of the active ingredient did not lead to adverse effects in the short or medium term.

Poliartrite em cão por Leishmaniose - tratamento com miltefosina / Polyarthritis in a dog due to leishmaniasis - treatment with miltefosine

Background: Canine visceral leishmaniasis causes several clinical signs, such as lymphadenomegaly, exfoliative dermatitis, ulcerative skin lesions, and lameness. The most commonly reported locomotor changes are claudication, edema, arthralgia, joint stiffness, and muscle atrophy. Radiographic exam revealed cortical and medullary destruction, increase, or decrease in medullary opacity, proliferative periosteal reaction, osteolysis, collapse of joint spaces and soft tissue edema are observed. The aim of this report is to describe the clinical and radiographic evolution of a case of erosive polyarthritis associated with leishmaniasis in a dog before, during and after treatment with miltefosine. Case: A 7-month-old mixed-breed dog was attended due pain and limited mobility. In the orthopedic evaluation, joint swelling, stiffness, and increased pain sensitivity of the four limbs, as well as neck stiffness, were noted. Radiographic examination showed joint changes compatible with edema, with increased volume and radiopacity of the soft tissues adjacent to the joints. The segments of the patient's spine showed more severe bone alterations, the cervical spine being one of the most affected regions, with multiple bone proliferations throughout the vertebral body, especially in the ventral portion (spondylosis), compatible with polyarthritis due to leishmaniasis. Due to the suspicion, lymph node and spleen cytology was performed, confirming the diagnosis. Hematological examination revealed anemia, leukopenia due to lymphopenia and thrombocytopenia in addition to increased AST (79,4 U/L; reference: 6,2 - 13 U/L), creatine kinase (517,6 U/L; reference: 1,5 - 28,4 U/L), lactate dehydrogenase (688,4 IU/L; reference: 45 - 233 IU/L) and hyperproteinemia (7,34 g/dL; reference: 5,4 - 7,1 g/dL). Treatment with miltefosine, allopurinol, domperidone, prednisone, gabapentin and dipyrone was started. Reassessments were performed monthly for 3 consecutive months. Hematological examinations showed improvement, with resolution of anemia and thrombocytopenia, and a marked decrease in creatine kinase values. Thus, it is evident that the dog did not develop liver or kidney changes during treatment. During the treatment and monitoring in this period, the dog had a clinical improvement, which started to walk without pain. In addition, joint swellings were no longer present, however, there was no improvement in the radiographic evaluation of the joints. Discussion: Clinical signs of the locomotor system are compatible with those described in animals that had osteoarticular manifestations associated with leishmaniasis, such as arthralgia, edema, and joint stiffness. In the present report, treatment with miltefosine associated with allopurinol resulted in an improvement in the clinical picture, and this therapy is therefore promising in dogs with polyarthritis due to leishmaniasis. A case published in human medicine demonstrated the intra-articular absorption capacity of this drug. There is only one study to date that describes the radiographic evolution of a dog with arthritis due to leishmaniasis after treatment with miltefosine and allopurinol. In this case described, the dog reported remained with the osteoarticular lesions after treatment, although clinical improvement was observed, as in our report. The use of miltefosine and allopurinol are in accordance with stage II staging for leishmaniasis. In this study, although there was no improvement in the radiographic examinations, the treatment was effective in the remission of the animal's clinical condition.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Evaluation of the antinociceptive effect generated by citronellal monoterpene isomers / Avaliação do efeito antinociceptivo gerado por isômeros do monoterpeno citronelal

Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.

Devido à natureza complexa da dor e a sua participação de aspectos físicos, cognitivos, psicológicos e comportamentais, o manejo da dor possui diversas abordagens. O uso de plantas medicinais em países em desenvolvimento é bastante expressivo. Buscando novas opções para o tratamento de denças emergentes ou debilitantes. Portanto, o presente estudo busca elucidar os efeitos do monoterpeno, citronelal, diferenciando sua atividade pelos isômeros (R)-(+) e (S)-(-) citronelal. O estudo utilizou diversos métodos para avaliar os efeitos dos isômeros de citronelal na coordenação motora, resposta nociceptiva e o envolvimento de vias opioides, glutamatérgicas e de receptores transitórios. Os métodos incluíram testes de rota-rod, placa quente e formalina, além do uso de inibidores e agonistas específicos. Os dados foram analisados estatisticamente com um intervalo de confiança de 95%. Ambos os isomeros não afetaram significativamente a coordenação motora dos animais em estudo. O isômero (S)-(-) citronelal apresentou melhores resultados em relação ao seu homólogo estrutural, conseguindo ter um efeito antinociceptivo nos testes de formalina e placa quente com menor concentração (100 mg/kg) e apresentando menos efeitos colaterais, entretanto, o presente estudo não foi capaz de elucidar o mecanismo de ação deste isomero apesar de ter atividadade em estudos com substancias que agem em alvos específicos como glutamato e capsaicina, sua atividade não foi revertida com a utilização de antagonistas para as vias relacionadas à nocicepção. Enquanto o isômero (R)-(+) citronelal, apesar de apresentar de apresentar total atividade somente na concentração de 150 mg/kg, foi capaz de determinar seu mecanismo de ação relacionado à via opióide pela reversão da sua atividade pelo antagonista naloxona, sendo esta uma via já correlacionada com os tratamentos de controle da a nocicepção, no entanto, também está relacionada a alguns efeitos colaterais indesejados. Desta forma busca-se novos estudos para elucidação do mecanismo relacionados ao isomero (S)-(-) citronellal e uma possibilidade de utilização em outras areas relacionadas ao tratamento da dor ou inflamação.

Cell therapy with adipose tissue-derived human stem cells in the urinary bladder improves detrusor contractility and reduces voiding residue / A terapia celular com células-tronco humanas derivadas do tecido adiposo na bexiga urinária melhora a contratilidade do detrusor e reduz o resíduo miccional

Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.

A Hipocontratilidade Detrusora (HD) é uma doença sem um tratamento padrão-ouro na medicina tradicional. Logo, há a necessidade de desenvolvimento de terapias inovadoras. O presente relato apresenta um caso de paciente com HD transplantado duas vezes com 2 x 106 células-tronco mesenquimais derivadas do tecido adiposo que obteve melhoras significativas em sua qualidade de vida. Os resultados demonstraram que a terapia celular reduziu o resíduo miccional de 1.800mL para 800mL; a Capacidade Cistométrica Máxima de 800 para 550mL; a complacência de 77 para 36,6mL/cmH2O. A terapia celular também aumentou o fluxo máximo de 3 para 11mL/s; a pressão detrusora de 08 para 35cmH2O; o volume urinado de 267 para 524mL e o índice de contratilidade vesical (BCI) de 23 para 90. O score do International Continence on Incontinence Questionare - Short Form passou de 17 para 8. Diante do exposto, infere-se que o transplante de células-tronco mesenquimais derivadas do tecido adiposo é uma estratégia terapêutica inovadora e eficiente para o tratamento da HD e para melhoria da qualidade de vida de pacientes acometidos por essa doença.

Molecular docking, ADMET and molecular dynamics simulation revealed metralindole as a multitargeted inhibitor for division kinases / Ancoragem molecular, ADMET e simulação de dinâmica molecular revelaram o metralindol como inibidor multialvo para divisão quinases

Lung cancer is the most common type of cancer in the world, and alone, in 2020, almost 2.21 million new cases were diagnosed, with 1.80 million deaths, and are increasing daily. Non-small cell lung (NSCLC) is the primary type of lung cancer, predominantly forms around 80% of cases compared to small cell carcinoma, and about 75% of patients are already in an advanced state when diagnosed. Despite notable advances in early diagnosis and treatment, the five-year survival rate for NSCLC is not encouraging. Therefore, it is crucial to investigate the molecular causes of non-small cell lung cancer to create more efficient therapeutic approaches. Lung cancer showed a more significant and persistent binding affinity and energy landscape with the target CDK2 staurosporine and FGF receptor-1. In this study, we have picked two essential target proteins, human cyclin-dependent kinase-2 and Human Protein Kinase CK2 Holoenzyme and screened the entire prepared DrugBank prepared library of 1,55,888 compounds and identified 2-(2-methyl-5-nitroimidazole-1-yl) ethanol (Metralindole) as a major inhibitor. Metralindole has displayed high docking scores of -5.159 Kcal/mol and -5.99 Kcal/mol with good hydrogen bonding and other bonding topologies such as van der Waals force, and ADMET results shown excellent bioavailability, outstanding solubility, no side effects, and toxicity. The molecular dynamics simulation for 100ns in a water medium confirmed the compound's stability and interaction pattern with the lowest deviation and fluctuations. Our in-silico study suggests Metralindole, an experimental compound, can effectively cure lung cancer. Further, the experimental validation of the compound is a must before any prescription.

O câncer de pulmão é o tipo de câncer mais comum no mundo, e, apenas em 2020, foram diagnosticados quase 2,21 milhões de novos casos, com 1,8 milhão de óbitos, e isso vem aumentando diariamente. O câncer de pulmão de células não pequenas (CPCNP) é o tipo primário de câncer de pulmão, forma que predomina em cerca de 80% dos casos em comparação com o carcinoma de pequenas células, e cerca de 75% dos pacientes já estão em estado avançado quando diagnosticados. Apesar dos avanços notáveis no diagnóstico e tratamento precoces, a taxa de sobrevida em cinco anos para CPCNP não é animadora. Portanto, é crucial investigar as causas moleculares do CPCNP para criar abordagens terapêuticas mais eficientes. O câncer de pulmão mostrou uma afinidade de ligação e perfil energético mais significativos e persistentes com a estaurosporina CDK2 alvo e o receptor-1 de FGF. Neste estudo, escolhemos duas proteínas-alvo essenciais, a quinase dependente de ciclina humana-2 e a holoenzima CK2 da proteína quinase humana, examinamos toda a biblioteca preparada pelo DrugBank de 1,55,888 compostos e identificamos 2-(2-metil-5-nitroimidazol-1-il) etanol (metralindol) como inibidor principal. O metralindol apresentou altas pontuações de ancoragem de -5,159 Kcal/mol e -5,99 Kcal/mol, com boas ligações de hidrogênio e outras topologias de ligação, como a força de Van der Waals, e os resultados do ADMET mostraram excelente biodisponibilidade e solubilidade, sem efeitos colaterais e toxicidade. A simulação de dinâmica molecular para 100ns em meio aquoso confirmou a estabilidade e o padrão de interação do composto com os menores desvios e flutuações. Nosso estudo in silico sugere que o metralindol, um composto experimental, pode efetivamente curar o câncer de pulmão. Além disso, a validação experimental do composto é obrigatória antes de qualquer prescrição.

Uso de soro autólogo no tratamento de úlcera ocular em cães: uma revisão bibliográfica / Use of autologus serum in the treatment of ocular ulcers in dogs: a bibliographic review / Uso de suero autólogo em el tratamiento de úlceras oculares em perro: una revisión bibliográfica

Sendo considerada uma doença de alto acometimento na oftalmologia veterinária de cães, a úlcera de córnea é um distúrbio caracterizado por uma ferida exposta na região corneal do olho. Os sinais são variados conforme o grau de agressividade da lesão, acarretando em perda da visão caso a intervenção não seja iniciada imediatamente. Devido a estes fatores e ao elevado nível de importância da doença, torna-se necessário o uso de terapêuticas que auxiliem o processo de reparo ocular, como a utilização do soro autólogo. Essa substância realiza uma função de evitar degradação da córnea e diminuir os sinais inflamatórios, o que torna essa prática um apoio eficaz para a finalização do tratamento, além de ser barato e de fácil acesso. Levando essas informações em consideração, o presente artigo realiza uma revisão com base em publicações apresentando o soro autólogo como um elemento adicional para o paciente poder concluir o tratamento de úlcera de córnea em menor tempo e com maior qualidade, retomando-o ao seu estado saudável.(AU)

Being considered a disease of high involvement in the veterinary ophthalmology of dogs, the corneal ulcer is a disorder characterized by an exposed wound in the corneal region of the eye. The signs vary according to the degree of aggressiveness of the lesion, leading to loss of vision if intervention is not started immediately. Due to these factors and the high level of importance of the disease, it becomes necessary to use therapies that help in the process of ocular repair, such as the use of autologous serum. This substance performs a function of preventing corneal degradation and reducing inflammatory signs, which makes this practice an effective support for the completion of treatment, besides being cheap and easily accessible. Taking this information into consideration, the present article performs a review based on publications presenting the autologous serum as an additional element for the patient to finish the corneal ulcer treatment in less time and with higher quality, returning him to his healthy state.(AU)

Siendo considerada una enfermedad de alto ataque en la oftalmología veterinaria de perros, la úlcera de córnea es una alteración caracterizada por una herida expuesta en la región corneal del ojo. Los signos son variados según el grado de agresividad de la lesión, acarreando en pérdida de la visión en caso de que la intervención no sea iniciada inmediatamente. Debido a estos factores y al alto nivel de importancia de la enfermedad, es necesario utilizar terapias que ayuden al proceso de reparación ocular, como el uso de suero autólogo. Esta sustancia cumple una función de evitar la degradación corneal y disminuir los signos inflamatorios, lo que hace de esta práctica un apoyo eficaz para el final del tratamiento, además de ser barata y de fácil acceso. Teniendo en cuenta esta información, el presente artículo realiza una revisión basada en publicaciones que presentan el suero autólogo como un elemento adicional para que el paciente finalice el tratamiento de la úlcera corneal en menor tiempo y con mayor calidad, devolviéndolo a su estado saludable.(AU)

Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved

Background: Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite. Methods: We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart. Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression. Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.

Potential of marine compounds in the treatment of neurodegenerative diseases: a review / Potencial de compostos marinhos no tratamento de doenças neurodegenerativas: uma revisão

Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.

As doenças neurodegenerativas (ND) são caracterizadas, especialmente, pela perda progressiva de neurônios, resultando em disfunções neuropsicomotoras. Mesmo apresentando uma alta prevalência, as DN são tratadas com medicamentos que aliviam os sintomas dos pacientes, mas que desenvolvem eventos adversos e ainda não inibem a progressão da doença. Assim, dentro de uma nova perspectiva farmacológica, esta revisão teve como objetivo verificar o potencial terapêutico de compostos naturais de origem marinha frente às DN. Para tal, foi realizada uma revisão integrativa, segundo a metodologia PRISMA que compreendeu etapas como: busca, pré-seleção e inclusão dos artigos. Os resultados descritos revelaram espécies como, Acaudina malpodioides, Holothuria scabra e Xylaria sp., que apresentaram importantes evidências em relação ao Alzheimer, reduzindo a geração de ROS, apresentando efeitos neuroprotetores e reduzindo a concentração de peptídeo Aß. Sobre a doença de Parkinson (PD), outro exemplo de ND, os compostos bioativos da Holothuria scabra e da Xylaria sp., mostraram ser capazes de diminuir a degeneração de neurônios dopaminérgicos, reduzir a deposição de alfa sinucleína e reduzir a formação de agregados da proteína Huntingtina mutante (Mhtt). Os outros compostos marinhos e substâncias bioativas também são descritos nesta revisão. Em conclusão, os estudos avaliados indicam que os compostos de origem marinha despontam como uma promissora fonte de compostos bioativos, revelando um importante potencial terapêutico para o tratamento das ND.

Lomustine for treatment of canine transmissible venereal tumor / Eficácia da lomustina no tratamento do tumor venéreo transmissível canino

Canine transmissible venereal tumor (TVTC) is a highly casuistic transmissible neoplasm in Brazil. Chemotherapy with vincristine sulfate is considered the treatment of choice, but the need for weekly applications and hematological monitoring, in addition to costs, are obstacles to owners' adhesion to the treatment. Lomustine is an alkylating class antineoplastic agent, and because it is administered orally, it is a more practical and less costly treatment option for the owners of animals with neoplasms sensitive to the drug. This study evaluated the therapeutic efficacy of lomustine in dogs affected by TVTC. Twelve dogs with cytopathological diagnosis of natural genital TVTC were selected. The dogs were submitted to the experimental protocol with lomustine administration at doses of 70 to 85 mg/m2 orally every 21 days, totaling a maximum of two administration cycles. The animals were reevaluated every 7 days until a maximum of +49 days after the first dose of lomustine, to monitor the regression of neoplastic lesions through measurements. Among the 12 dogs submitted to the lomustine protocol, 8/12 achieved complete remission of the neoplasm and were considered cured (66.6%), 1/12 had partial response to treatment (8.33%) and 3/12 had stable disease (25%). Important adverse effects such as severe neutrophilic leukopenia were detected in 3/12 dogs (25%). The clinical study indicated that lomustine may be a treatment option for TVTC.

O tumor venéreo transmissível canino (TVTC) é uma neoplasia transmissível de elevada casuística no Brasil. A quimioterapia com sulfato de vincristina é considerada o tratamento de escolha, mas a necessidade de aplicações semanais e acompanhamento hematológico, além dos custos, são obstáculos à adesão dos proprietários ao tratamento. A lomustina é um antineoplásico da classe dos agentes alquilantes e, por ser administrado por via oral, representa um opção de tratamento mais prática e menos onerosa para os proprietários de animais com neoplasias. O objetivo deste estudo foi avaliar a eficácia terapêutica da lomustina em cães acometidos por TVTC. Foram selecionados 12 cães com diagnóstico citopatológico de TVTC genital de ocorrência natural. Os cães foram submetidos ao protocolo experimental com administração de lomustina nas doses de 70 a 85 mg/m2 por via oral a cada 21 dias, totalizando no máximo dois ciclos de administração. Os animais foram reavaliados a cada sete dias até um máximo de +49 dias após a primeira dose de lomustina, para monitorar a regressão das lesões neoplásicas por meio de mensuração das lesões. Entre os 12 cães submetidos ao protocolo, 8/12 obtiveram remissão completa da neoplasia e foram considerados curados (66,6%), 1/12 tiveram resposta parcial ao tratamento (8,33%) e 3/12 tiveram doença estável (25%). Efeitos adversos importantes, como leucopenia neutrofílica grave, foram detectados em 3/12 cães (25%). O estudo clínico indicou que a lomustina pode ser uma opção de tratamento para TVTC.

Glaucoma in dogs and cats - management with cyclocryotherapy

Background: The treatment of glaucoma often requires numerous therapeutic modalities to achieve the desired reduction in intraocular pressure (IOP). Cyclodestructive procedures or ciliary body destruction have been performed using techniques with considerable differences in efficacy and complication rates. Among these methods, cyclocryotherapy is non-invasive and simple for the management of uncontrolled glaucoma in dogs and cats. The objective of this case report is to describe the technique of carbon dioxide cyclocryotherapy to reduce intraocular pressure in dogs and cats with glaucoma. Cases: Nine canine patients and one cat with glaucoma were treated with cyclocryotherapy performed under general anaesthesia. Clinical signs patients included blepharospasm, ocular pain, episcleral congestion and ocular hypertension. The patients showed higher levels of IOP, higher than 30 mmHg. Surgical treatment with general anaesthesia was applied. The pre-anaesthesia protocol included acepromazine 0.05 mg/kg with methadone 0.2 mg/kg, followed by intravenous propofol and maintenance with isoflurane and oxygen. An ophthalmological cryocautery unit was used with carbon dioxide as the cryogenic agent and a retinal cryoprobe of 3.2 mm diameter tip for the procedure. The method used was a double cycle of freezing and thawing for 60 s in each site. The cryoprobe was centred approximately 5 mm posterior to the corneoscleral limbus over the ciliary body. The temperature of each cyclocryotherapy spot was between -60°C and -80°C and each site was maintained in place for 60 s; 4 to 6 spots of the double freeze-thaw cycle were made. This technique did not have any serious complications during or after the application of cryotherapy, but chemosis and hyperaemia of the bulbar conjunctiva developed. Subconjunctival anti-inflammatory steroids were injected to minimise swelling and patient discomfort. Satisfactory results were observed; in all cases, the intraocular pressure decreased, with the usual result being a cosmetic and painless eye. Discussion: Even with recent surgical and medical advances, pain and blindness are still common occurrences in glaucoma in human and veterinary practice. The cyclodestructive procedures included cyclodialysis, cyclodiathermy, cyclocryotherapy, and cyclophotocoagulation. The cryosurgery in veterinary ophthalmology has many indications for the treatment of ocular diseases and is effective at decreasing intraocular pressure in patients with persistent uncontrolled glaucoma. Cyclocryotherapy has been shown to reduce intraocular pressure in dogs, cats, rabbits and humans with normotensive and glaucomatous eyes. The application of a cryoprobe over the ciliary processes results in ablating ciliary tissue so that aqueous humour inflow is reduced to acceptable levels. In the clinical cases evaluated, there was a reduction in intraocular pressure reaching acceptable levels, with the usual result being cosmetic and painless eye. Medical therapy remains the predominant method for treating glaucoma in veterinary patients; therefore, cyclocryotherapy is an effective, simple way to lower IOP and is a reasonable treatment option for glaucoma management. Cyclocryotherapy has shown good results, with a low learning curve and it can also be repeated if necessary.

Use of convalescent plasma to treat COVID-19: case studies / Uso de plasma convalescente para tratar COVID-19: estudos de caso

There have been several efforts to minimize the effects caused by the COVID-19 virus around the world. Vaccines were developed in record time and alternative therapies were studied and applied in several countries, such as the use of plasma from recovered patients. Identifying, systematically evaluating and summarizing the best available scientific evidence on the efficacy and safety of using plasma from recovered COVID-19 patients remains the objective of this study. The studies carried out showed that the application of convalescent plasma contributes to the reduction of mortality, viral load and length of hospital stay. However, the effectiveness of the therapy still raises doubts due to the number of patients evaluated in clinical studies, in addition to its high cost and limitations in terms of availability and implementation, with the drug being authorized only for hospital use.

Houve vários esforços para minimizar os efeitos causados pelo vírus COVID-19 em todo o mundo. As vacinas foram desenvolvidas em tempo recorde e terapias alternativas foram estudadas e aplicadas em vários países, como o uso de plasma de pacientes recuperados. Identificar, avaliar sistematicamente e resumir as melhores evidências científicas disponíveis sobre a eficácia e segurança do uso de plasma de pacientes recuperados com COVID-19 continua sendo o objetivo deste estudo. Os estudos realizados mostraram que a aplicação de plasma convalescente contribui para a redução da mortalidade, carga viral e tempo de internação hospitalar. No entanto, a eficácia da terapia ainda gera dúvidas devido ao número de pacientes avaliados em estudos clínicos, além de seu alto custo e limitações em termos de disponibilidade e implementação, sendo o medicamento autorizado apenas para uso hospitalar.