Tratamento da hepatite C em pacientes com doença renal crônica e pós-tranplante renal: eficácia e segurança dos esquemas de antivirais de ação direta contendo sofosbuvir / Hepatitis c treatment of renal transplant and chronic kidney disease patients: efficacy and safety of direct-acting antiviral regimens containing sofosbuvir

ABSTRACT BACKGROUND: Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients with glomerular filtration rate (GFR) <30 mL/min. OBJECTIVE: To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients. METHODS: All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification. RESULTS: A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively. CONCLUSION: The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.

RESUMO CONTEXTO: Os antivirais de ação direta revolucionaram o tratamento da hepatite C, inclusive para os pacientes com doença renal crônica (DRC), porém ainda há divergências no emprego do sofosbuvir (SOF) quando taxa de filtração glomerular (TFG) <30 mL/min. OBJETIVO: Avaliar a eficácia e segurança desses esquemas no tratamento da hepatite C em pacientes com DRC e pós-transplante renal, além de avaliar o impacto do SOF sobre a função renal dos não-dialíticos. MÉTODOS: Todos os pacientes com hepatite C e DRC ou transplante renal que realizaram tratamento com antivirais de ação direta em centro referenciado do Brasil no período de janeiro/2016 a agosto/2017 foram incluídos. A eficácia foi avaliada por meio da carga viral (HCV-RNA), considerando-se cura uma resposta virológica sustentada (RVS) com resultado indetectável após 12 e/ou 24 semanas do término do tratamento (RVS12 e RVS24). A segurança foi determinada pelos eventos adversos e a ribavirina, quando associada, foi introduzida de forma escalonada em todos os pacientes com TFG <60 mL/min. Para determinação do impacto do SOF sobre a função renal, foram observadas as dosagens de creatinina basal, durante e após término do tratamento com seu incremento avaliado por meio da classificação de AKIN (acute kidney injury network). RESULTADOS: Foram incluídos 241 pacientes, sendo 52,7% do sexo feminino, com média de idade de 60,72±10,47 anos. A associação de SOF+daclatasvir predominou em 75,6% dos casos e anemia esteve presente em 28% dos pacientes que utilizaram ribavirina (P=0,040). As taxas de RVS12 e RVS24 foram de 99,3% e 97,1%. O tratamento foi bem tolerado, com eventos adversos pouco relevantes, sendo os mais prevalentes: astenia (57,7%), prurido (41,1%), cefaleia (40,7%) e irritabilidade (40,2%). Entre os pacientes em tratamento conservador e transplantados renais, os valores de creatinina sofreram oscilações AKIN I em 12,5% dos casos, durante o tratamento, persistindo em apenas 8,5% da amostra após o término, dos quais 2,0% apresentavam TFG <30 mL/min inicialmente, com queda para 1,1% após uso do SOF. Apenas 0,5% e 1,6% evoluíram com elevação AKIN II e AKIN III. CONCLUSÃO: Os antivirais de ação direta foram seguros e eficazes em pacientes com DRC tratados com esquemas contendo SOF, apresentando altas taxas de RVS, boa tolerabilidade e poucos eventos adversos graves. A associação com ribavirina aumentou o risco de anemia, portanto sua introdução de forma escalonada parece ser útil nos pacientes com TFG <60 mL/min. Em pacientes com TFG <30 mL/min o SOF não apresentou impacto renal significativo, com creatinina sérica retornando a valores próximos ao basal após o tratamento.

Combined ns5a & ns5b nucleotide inhibitor therapy for patients with chronic hepatitis c with stage 5 chronic kidney disease on hemodialysis / Terapia inibidora de nucleotídeo NS5A& NS5B combinada para pacientes com hepatite C crônica com doença renal crônica em estágio 5, em hemodiálise

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é a infecção viral hepática mais comum que afeta pacientes em hemodiálise de manutenção. O tratamento da infecção crônica por HCV no estágio 4 e 5 da doença renal crônica inclui uma combinação de elbasvir/grazoprevir e glecaprevir/pibrentasvir, que não estão disponíveis em muitos países. OBJETIVO: Portanto, realizamos este estudo para procurar a segurança e eficácia da terapia combinada de sofosbuvir nesta população de difícil tratamento. MÉTODOS: Realizamos um estudo de centro único, prospectivo e aberto, no qual pacientes com doença renal crônica em estágio 5 em hemodiálise de manutenção com infecção por HCV. Um total de 18 pacientes foi incluído. Sofosbuvir com daclatasvir ou ledipasvir foi usado de acordo com o genótipo por 12 semanas. O HCV RNA, genótipo, elastografia transitória foi considerado para cada paciente. O HCV RNA foi quantificado na 4ª semana, 12ª semana e 12 semanas após o tratamento para procurar uma resposta virológica sustentada. RESULTADOS: A infecção por genótipo 1 foi observada em 12 (66,7%) pacientes, seguido pelo genótipo 3 em 4 (22,3%), em um paciente do genótipo 2 e em outro, 5. O valor mediano do HCV RNA foi de 2.35.000 IU/mL. Na elastografia transitória, todos tinham rigidez hepática de <9.4 KPa. Todos os pacientes tinham RNA HCV <15 IU/mL na 4ª e 12ª semana de tratamento e 12 semanas após o tratamento. Não foi observada nenhuma alteração significativa na hemoglobina, eGFR e rigidez hepática. CONCLUSÃO: A dose completa sofosbuvir ou seja, 400 mg, em combinação com inibidores NS5A daclatasvir ou ledipasvir foi considerada segura e eficaz em pacientes com doença renal em estágio final, que estão em manutenção hemodiálise.

Paniculitis secundaria a terapia target en paciente con melanoma, lo que el dermatólogo debe saber: reporte de un caso / Panniculitis in association with target therapy in melanoma patient, what the dermatologist should know: a case report

Las terapias target constituyen hoy en día una alternativa terapéutica cada vez más utilizada para el manejo de pacientes con melanoma metastásico. Sin embargo, se han descrito múltiples efectos farmacológicos adversos asociados a su uso, siendo los cutáneos los de mayor prevalencia. Se presenta el caso de un hombre de 55 años con diagnóstico de melanoma cutáneo metastásico etapa IV, BRAFV600E mutado, en tratamiento con dabrafenib/trametinib que consultó por desarrollo de lesiones nodulares eritematosas sensibles en extremidades superiores e inferiores, asociadas a sensación febril durante el curso del tratamiento. Se descartó alguna infección sobreagregada. Se realizó una biopsia de las lesiones cutáneas, con confirmación diagnóstica histopatológica de una paniculitis mixta de predominio septal, granulomatosa y con vasculitis leucocitoclástica. La paniculitis asociada a esta terapia ha sido descrita en la literatura y se ha considerado un efecto farmacológico inmunomediado adverso, relacionándose a un mejor pronóstico para el melanoma metastásico en tratamiento. Por lo tanto, así como en el caso presentado, se evita la suspensión del fármaco y se asocia terapia sintomática en caso de mayores molestias del paciente. Es de alta relevancia para el dermatólogo conocer e interpretar adecuadamente este efecto adverso farmacológico, y así indicar el manejo más adecuado para el paciente.

Target therapies are currently a therapeutic option increasingly used for the management of patients with metastatic melanoma. However, there are multiple adverse pharmacological effects associated with their use that have been described. Cutaneous adverse reactions are the most frequent. We report the case of a 55-year-old man with a diagnosis of stage IV BRAFV600E-mutated metastatic cutaneous melanoma undergoing treatment with dabrafenib/trametinib, who consulted due to the development of erythematous nodular lesions in the upper and lower limbs associated with febrile sensation during the course of treatment. Infection was ruled out and a biopsy of the skin lesions was done, which provided the histopathological confirmation of a predominantly septal, granulomatous with leukocytoclastic vasculitis, mixed panniculitis. Panniculitis associated with this therapy has been described in the literature and has been considered an immune-mediated pharmacological adverse effect. It is considered to be related to a better prognosis in the treatment of metastatic melanoma. Consequently, as shown in this case report, target therapy should not be discontinued and symptomatic medication should be given to alleviate patient discomfort. The dermatologist should know and properly interpret this adverse effect and prescribe the most appropriate management for the patient.

Primer reporte de caso autóctono de tinea nigra en Chile / First autochthonous case report of tinea nigra in Chile

Resumen La tinea nigra es una infrecuente micosis superficial causada por el hongo dematiáceo Hortaea werneckii. Se presenta habitualmente en zonas costeras tropicales, siendo muy escasos los reportes en países sudamericanos con climas más templados. Habitualmente corresponde a infecciones importadas por viajeros. Se presenta el caso de una paciente adulta chilena, sin historia previa de viajes recientes, cursando con cuadro clínico y microbiológico compatible con tinea nigra palmar, tratado con itraconazol oral y sertaconazol tópico con respuesta favorable. Esta paciente corresponde al primer caso reportado en Chile de origen autóctono.

Abstract Tinea nigra is an infrequent superficial mycosis caused by the dematiaceous fungus Hortaea werneckii. It usually occurs in tropical coastal areas, with very few reports in South American countries with temperate climates, generally corresponding to infections imported by travelers. We present the case of a Chilean adult patient, with no previous history of recent trips, with clinical and microbiological background consistent with palmar tinea nigra, treated with oral itraconazole and topical sertaconazole with a favorable response. This article is the first case reported in Chile, of autochthonous origin.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Efeito da terapia de longa duração com ácido zoledrônico no osso esponjoso da mandíbula e fêmur de ratos Wistar / Effect of long-term zoledronic acid treatment on cancellous bone in the mandible and femur of Wistar rats

Os bisfosfonatos (BF) são amplamente utilizados no tratamento de doenças osteolíticas como metástases ósseas e osteoporose. A osteonecrose dos maxilares associada ao uso de BF (OMAB) é caracterizada pela presença de osso exposto ou que pode ser sondado através de uma fístula que persiste por mais de oito semanas em pacientes com história de terapia de BF e sem história de radioterapia na região de cabeça e pescoço e/ou sem doença metastática nos maxilares. A incidência de OMAB aumenta com a potência, duração do tratamento e dose de BF recebida. Até o presente momento, a fisiopatologia da OMAB não está clara, dificultando a prevenção e o tratamento. O objetivo deste estudo foi avaliar o efeito da administração de altas doses Ácido Zoledrônico (AZ) por período prolongado no osso esponjoso da mandíbula e da metáfise proximal do fêmur de ratos Wistar. Para relacionar as descobertas à fisiopatologia da OMAB, o regime de administração de BF de um modelo animal relevante desta lesão foi reproduzido. Seis animais receberam AZ (0,6 mg / kg) e seis receberam solução salina no mesmo volume (Controles). Os compostos foram administrados por via intraperitoneal em cinco doses a cada 28 dias. A eutanásia dos animais ocorreu após 150 dias de início da terapia. As hemimandíbulas e fêmures direitos foram escaneados usando Micro-tomografia computadorizada (Micro-CT) de alta resolução (14 m). Para a primeira análise realizada neste estudo, os dados morfométricos do osso esponjoso foram calculados na região do segundo e primeiro molar na mandíbula e na metáfise do fêmur usando CTAnalyzer (Bruker, Bélgica). Para a segunda análise, cinco amostras de hemimandíbulas de cada grupo foram cortadas em lâminas histológicas (5 m) e coradas com Hematoxilina e Eosina. Para comparar os parâmetros morfométricos na Micro-CT e histologia, as imagens de Micro-CT foram espacialmente alinhadas à histologia. Os dados morfométricos do osso alveolar foram calculados usando o software CTAnalyzer (Bruker, Bélgica) na região entre as raízes mesial e distal do primeiro molar. A densidade da área vascular (área vascular/área total; VA/TA) e os dados histomorfométricos ósseos foram estimados usando Axiovision na mesma região (entre as raízes mesial e distal do primeiro molar). Foi adotada significância estatística de 5% ( = 0,05). Os animais tratados com AZ apresentaram aumento significativo na porcentagem de volume ósseo (p <0,05) com trabéculas mais espessas, osso mais compacto com menor separação trabecular na mandíbula e no fêmur. Na mandíbula, o aumento da densidade óssea e diminuição da separação trabecular foram fortemente correlacionados com a diminuição da área vascular observada no grupo AZ (p <0,05). Em conclusão, o tratamento de longa duração com altas doses de AZ foi significativamente associado ao aumento na densidade óssea e à diminuição dos espaços medulares, canais nutritivos e vasculatura do osso alveolar. A análise com Micro-CT revelou alterações semelhantes na estrutura óssea tanto na mandíbula quanto no fêmur do grupo AZ.(AU)

Bisphosphonates (BFs) are widely used in the treatment of osteolytic diseases such as bone metastases and osteoporosis. The osteonecrosis of the jaws related to BF (ONB) is characterized by the presence of exposed bone or bone that can be probed through a fistula that persists for more than eight weeks in patients with a history of BF therapy and without history of head and neck radiotherapy and / or without metastatic disease in the jaws. The incidence of ONB increases with potency, duration of treatment and dose of BF received. Thus far, the pathophysiology of ONB is unclear, hampering prevention and treatment. The aim of this study was to objectively assess the effect of long-term high-dose Zoledronic Acid (ZA) on cancellous bone in the jaw and femur of Wistar rats. In order to link our findings to the physiopathology of ONB, the therapeutic regiment of a relevant ONB animal model was reproduced. Twelve Wistar rats were randomly divided in two groups: six received Zoledronic acid (ZA; 0.6 mg / kg) and six (Controls) received saline solution in the same volume. The compounds were administrated intraperitoneally in five doses each 28 days. The rats were killed after 150 days of the therapy onset. Mandibles and femurs were scanned using a high-resolution (14m) micro-computerized tomography (Micro-CT). For the first analysis carried in this study, cancellous bone morphometric data were calculates in the region of the second and first molar in the mandible and in the proximal femur using CTAnalyzer (Bruker, Belgium). For the second analysis five samples were cut into histological slices (5m) and stained with Hematoxylin and Eosin. In order to compare the same morphological structures in Micro-CT and histology, the Micro-CT images were aligned to histology. Alveolar bone morphometric data (Micro-CT) was calculated using CTAnalyzer (Bruker, Belgium) in the region between the mesial and distal roots of the first molar. Blood vessels density and bone histomorphometric data were calculated using Axiovision (Carl Zeiss, Germany) in the same region used for Micro-CT evaluation. Statistical significance of 5% (=0.05) was adopted. ZA treated rats presented significant increase in the percentage of bone volume (p<0.05) with thicker trabeculae and more compact bone with smaller marrow spaces in the mandible and femur. In the mandible, the increase in bone density and decrease of marrow spaces size was strongly correlated with the decrease in the vascular area noticed in the ZA group (p<0.05). In conclusion, long-term high-dose ZA treatment was significant associated with the increase of bone density and the diminution of medullary spaces and nutritive canals size as well as decrease in vascularity of the alveolar bone. Micro-CT investigation showed similar changes in bone structure in the mandible and femur in the ZA group.(AU)

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

ABSTRACT PURPOSE : To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS: Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS: Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS: The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Dimensoes internas nasais de adultos com obstrucao nasal / Internal nasal dimensions of adults with nasal obstruction

O desvio septal (DS) e a hipertrofia de conchas (HC) aumentam a resistência ao fluxo aéreo respiratório, podendo prejudicar a patência nasal. OBJETIVO: Caracterizar a geometria nasal de indivíduos com obstrução nasal (ON) por DS e/ou HC usando rinometria acústica. Forma de estudo: Clínico prospectivo. MÉTODO: Foram avaliados 30 adultos com queixa de ON e DS+HC (n = 24), DS (n = 5) ou HC (n = 1) ao exame clínico e determinadas as áreas seccionais transversas em três principais deflexões do rinograma (AST1, AST2, AST3), suas distâncias relativamente às narinas (dAST1, dAST2, dAST3) e os volumes dos segmentos 1,0-3,2 cm (V1), 3,3-6,4 cm (V2) e 7,0-12,0 cm (V3), pré e pós-descongestão nasal (DN). Foram consideradas, para análise, as somas de AST e V das cavidades direita e esquerda e a média de dAST. RESULTADOS: Os valores médios (± DP) pré-DN corresponderam a 0,83 ± 0,23 (AST1), 1,66 ± 0,52 (AST2) e 2,36 ± 0,77 (AST3) cm2, 2,19 ± 0,20 (dAST1), 4,01 ± 0,33 (dAST2) e 5,85 ± 0,37 (dAST3) cm, 2,77 ± 0,51 (V1), 6,52 ± 1,99 (V2), 26,00 ± 9,62 (V3) cm3, todos menores (p < 0,05) que valores de referência do laboratório. A DN causou aumentos proporcionalmente maiores neste grupo ON, sugerindo componente funcional associado. A análise individual mostrou 12 casos com resultados normais, apesar da ON. CONCLUSÃO: A maioria dos pacientes com ON estrutural apresentou resultados sugestivos de comprometimento da patência nasal ao exame rinométrico. .

Nasal septum deviation (SD) and turbinate hypertrophy (TH) increase the resistance to respiratory airflow and may impair nasal patency. OBJECTIVE: To characterize the nasal geometry of individuals with nasal obstruction secondary to SD and/or TH by means of acoustic rhinometry. METHOD: This prospective study included 30 adults with complaints of nasal obstruction (NO) and SD + TH (n = 24), SD (n = 5) or TH (n = 1) seen by clinical examination. The cross-sectional areas of the three main dips of the rhinogram (CSA1, CSA2, CSA3), the distance between them and the nostrils (dCSA1, dCSA2, dCSA3), and the volumes of segments 1.0-3.2 cm (V1), 3.3-6.4 cm (V2), and 7.0-12.0 cm (V3) were measured before and after nasal decongestion (DN). For analysis, right and left cross-sectional areas and volumes were added and mean dCSA was calculated. RESULTS: Mean values (standard deviation) before ND were: 0.83 ± 0.23 (CSA1), 1.66 ± 0.52 (CSA2), and 2.36 ± 0.77 (CSA3) cm2; 2.19 ± 0.20 (dCSA1), 4.01 ± 0.33 (dCSA2), and 5.85 ± 0.37 (dCSA3) cm; 2.77 ± 0.51 (V1), 6.52 ± 1.99 (V2), and 26.00 ± 9.62 (V3) cm3; all values were lower than laboratory reference values (p < 0.05). ND led to proportionally greater increases of sectional areas and volumes in the NO group, suggesting an associated functional component. Individual analysis revealed 12 cases with normal results despite nasal obstruction. CONCLUSION: Most patients with structural nasal obstruction had results suggestive of nasal patency impairment in acoustic rhinometry. .

First Feline Case of Otodectosis in the Republic of Korea and Successful Treatment with Imidacloprid/Moxidectin Topical Solution

In April 2010, pruritic symptoms were recognized in 3 privately-owned Siamese cats raised in Gwangju, Korea. Examination of ear canals revealed dark brown, ceruminous otic exudates that contain numerous live mites at various developmental stages. Based on morphological characteristics of adult mites in which caruncles were present on legs 1 and 2 in adult females and on legs 1, 2, 3, and 4 in adult males while the tarsus of leg 3 in both sexes was equipped with 2 long setae, the mite was identified as Otodectes cynotis. Ten ear mite-free domestic shorthaired cats were experimentally infected with O. cynotis to evaluate the efficacy of 10% imidacloprid/1% moxidectin spot-on. Live mites were recovered from 1 of 10 treated cats on day 9 post-treatment (PT) while no live mites were observed from the ear canals of treated cats on days 16 and 30 PT. The efficacy of 10% imidacloprid/1% moxidectin spot-on on O. cynotis in cats was, therefore, 90% on day 9 and 100% on days 16 and 30 PT. This is the first report of otodectosis in 3 cats naturally infested with O. cynotis in Gwang-ju, Korea. Both natural and experimental infestations were successfully treated with 10% imidacloprid/1% moxidectin spot-on.

Efecto de una sola dosis de ácido zoledrónico en un caso de enfermedad de Paget ósea / Effect of a single dose of zoledronic acid in a case of Paget bone disease

La enfermedad de Paget es un trastorno crónico del remodelado óseo, caracterizado por un aumento de la resorción ósea producido por osteoclastos atípicos, seguido por un incremento acelerado de la formación ósea, lo que resulta en la formación de hueso en mosaico desorganizado. Un excelente marcador bioquímico para orientar el diagnóstico y seguimiento es la fosfatasa alcalina (FAL). Se presenta el caso de un paciente de 90 años, de sexo masculino, con diagnóstico de enfermedad de Paget. Se inicia tratamiento con pamidronato vía oral con respuesta parcial, por lo que se rota a pamidronato endovenoso. Disminuyen el dolor y la concentración plasmática de FAL, persistiendo con centellograma óseo patológico. Luego de varios años de tratamiento, con adecuado aporte de calcio y vitamina D, comienza nuevamente con dolor y valores elevados de FAL. Se decide iniciar tratamiento con ácido zoledrónico endovenoso 4 mg, única aplicación, obteniéndose remisión clínica y bioquímica desde hace cuatro años y mejoría de la imagen centellográfica. Este informe refiere la buena respuesta, sostenida en el tiempo, al tratamiento con única dosis de ácido zoledrónico en un paciente que presentó resistencia al pamidronato.

Paget's disease is a chronic disorder of bone remodeling characterized by increase of bone resorption by atypical osteoclasts, followed by rapid increase in bone formation resulting in a disorganized mosaic bone. The biochemical marker for early diagnosis and monitoring is serum alkaline phosphatase (ALP). We report the case of a 90 year old male, with diagnose of Paget's disease. Pamidronate treatment was started orally with partial response, so it was switched to intravenous pamidronate. Pain intensity and FAL levels diminished. The scyntigraphic scan, however, though improved, persisted abnormal. After several years of treatment, with adequate calcium and vitamin D support, the patient presents pain and increase of FAL. We administered intravenous zoledronic acid (4 mg) in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget´s disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.

Central serous chorioretinopathy after dacryocystorhinostomy operation on the same side.

A 43-year-old man developed central serous choroidoretinopathy in his left eye following dacryocystorhinostomy operation on the same side. He was using xylometazoline nasal drops in his left nostril. Action of xylometazoline or the stress related to the operation or the effect of both factors played the role in the causation of this ocular condition. Omission of nasal drops or relief from stress resulted in full recovery of vision and complete resolution of symptoms within one month.

Atividade in vitro de antifungicos frente a isolados de Malassezia spp. de animais atendidos no Hospital Veterinário da Unipar / Actividad in vitro de antifúngicos frente a aislados de Malassezia spp. de animales atendidos en el Hospital Veterinario de la UNIPAR / In vitro activity of antifungals against malassezia spp. isolates from animals assisted in the Unipar Veterinary Hospital

A otite externa em cães, na grande maioria das vezes, tem participação de espécies de Malassezia ssp. Fatores predisponentes e perpetuantes tornam esta levedura bastante importante, pois normalmente ocasiona uma otite recidivante. Drogas antifúngicas são amplamente utilizadas, porém a sua eficácia muitas vezes fica aquém do desejado. Considerando estes fatos, este estudo teve como objetivo estudar as concentrações inibitórias mínimas in vitro de cetoconazol e clorexidine, frente a isolados de Malassezia spp. Testes in vitro foram realizados e verificou-se que o cetoconazol necessita de uma menor concentração para inibir o crescimento de Malassezia spp., quando comparado ao clorexidine, mostrando-se mais eficiente.

External otitis in dogs usually present the occurance of species of Malassezia ssp. Predisponent and perpetuating factors make this yeast very important as it usually results in recurrent otitis. Antifungal drugs are largely used, however, their efficacy is usually above the expected. By considering these factors, the minimum inhibitory in vitro concentrations of cetoconazol against Malassezia spp. isolates were studied. In vitro tests were conducted and cetoconazol presented to be more efficient as it demands a lower concentration to inhibit the growth of Malassezia spp. when compared to clorexidine.

La otitis externa en perros, la mayoría de las veces, tiene participación de especies de Malassezia spp. Factores que predisponen y perpetúan esta levadura muy importante, pues normalmente ocasiona una otitis recidivante. Drogas antifúngicas son ampliamente utilizadas, sin embargo su eficacia muchas veces se queda aquende del deseado. Considerando estos hechos, este estudio tuvo como objetivo estudiar las concentraciones inhibitorias mínimas in Vitro de cetoconazol y clorhexidina, frente a aislados de Malassezia spp. Testes in Vitro fueron realizados y se verificó que el cetoconazol necesita de una menor concentración para inhibir el crecimiento de Malassezia spp., cuando comparado al clorhexidina, presentándose más eficiente.

Effectiveness of intravenous bisphosphonate in treatment of giant cell tumor: a case report and review of the literature.

Giant cell tumor is a benign locally aggressive tumor. The standard treatment is en bloc resection followed by major reconstructive surgery, or extended curettage conjunction with bone grafting or the use of bone cement implantations. Surgical treatment of giant cell tumor at the sacrum is associated with high morbidity, and local recurrence. The authors present a case of giant cell tumor at the sacrum treated with intravenous 4 mg zoledronate every 4 weeks for seven courses followed with curettage and cement implantation. At two years follow-up, the patient had no pain, no neurological deficit, and no local recurrence. The patient's gait was normal. From the present study, the authors demonstrate the effectiveness of zoledronate for treatment of giant cell tumor at the sacrum. It can reduce the morbidity from major surgery.

Bone metastasis in hepatocellular carcinoma: need for reappraisal of treatment.

Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.

Tratamento da doença de Paget óssea: importância do ácido zoledrônico / Treatment of Paget's disease of bone: importance of the zoledronic acid / Treatment of Paget's disease of bone: importance of the zoledronic acid

A doença de Paget é uma doença esquelética, de distribuição monostótica ou poliostótica, podendo ser causada por uma infecção viral e/ou fatores genéticos. É caracterizada por um aumento da remodelação óssea, resultando em anormalidade da arquitetura óssea. A excessiva reabsorção óssea osteoclástica, seguida secundariamente de aumento da atividade osteoblástica, leva à substituição do osso normal por osso desorganizado, aumentado, e com estrutura enfraquecida, propensa a deformidades e fraturas. A doença de Paget pode ser diagnosticada através de exames radiológicos, cintilografia e exames bioquímicos. O objetivo primário do tratamento é reduzir a dor e o risco do aparecimento das complicações a longo prazo. Atualmente dispõe-se de drogas anti-reabsortivas potentes, as quais controlam a reabsorção óssea e proporcionam uma grande melhora no tratamento. O ácido zoledrônico, um bisfosfonato de última geração, tem a vantagem de maior potência e remissão mais prolongada, além de um tempo de infusão curto.

Paget's disease is a localised monostotic or polyostotic bone disease of unknown origin. It may be caused by a slow viral infection and/or genetic factors. It is characterised by increased bone remodelling and an initially excessive osteoclastic bone resorption, followed by a secondary increase in osteoblastic activity, leading to replacement of the normal bone by a disorganized, enlarged, and weakened osseous structure prone to deformities and fractures. The disease may be diagnosed by radiography, scintigraphy and biochemical tests. The primary aim of treatment is to reduce pain and risk of developing long-term complications. Potent antiresorptive drugs are now available, which control the increased bone remodelling and have led to a dramatic improvement in treatment. Zoledronic acid, a new generation of bisphosphonates, has the advantage of great potency and long duration of remission and a short infusion time.

Histoplamose cutânea em gato: relato de caso / Cutaneous Histoplamose in cat: case story

Descreve-se um caso de histoplasmose cutânea em um gato, da raça Siamesa, com três anos de idade. O animal apresentava crescimento de aspecto esponjoso, sanguinolento, com secreção purulenta na região nasal, cuja evolução ocorreu em cerca de dois meses. O exame citológico revelou presença de Histoplasma capsulatum. O animal foi tratado com cetoconazol durante 20 dias, ocorrendo remissão completa dos sintomas.