Comparación de la eficacia y toxicidad del estibogluconato de sodio y antimoniato de meglumina en el tratamiento de leishmaniasis cutánea en Perú / Efficacy and safety of sodium stibogluconate compared to meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru

Objetivos : Comparar la eficacia y toxicidad del antimoniato de meglumina (AM) y estibogluconato sódico (EGS) en el tratamiento de leishmaniasis cutánea (LC) en un hospital general. Material y métodos : Serie de casos comparativa de 193 pacientes con LC tratados en tres ensayos clínicos con AM (n=69) y EGS (n=124) durante 2001-2010. La administración de ambas drogas fue vía endovenosa lenta de 20 mg Sb5+/kg/día por 20 días consecutivos siguiendo las normativas de la OPS y OMS. La información clínica, toxicidad y eficacia fue obtenida de las historias clínicas almacenadas en el centro de investigación según la normativa local e internacional. Resultados : Las características demográficas fueron similares entre grupos, pero el tamaño y número de lesiones fueron mayores en el grupo AM. La eficacia del tratamiento con AM fue 76,0% versus 68,4% con EGS (p=0,340) y 55,1% versus 50,8% (p=0,570) en el análisis por protocolo y de intención de tratar, respectivamente. No se observaron efectos adversos inmediatos. Los síntomas más frecuentemente reportados fueron disgeusia (37,0%), mareos (32,0%), cefalea (36,0%), artralgias (31,0%) y linfangitis (21,0%). Los tres primeros síntomas, así como elevación de transaminasas, leucopenia, trombocitopenia y QTc prolongado fueron frecuentes en el grupo EGS, pero clínica y estadísticamente no significativos. El tratamiento fue suspendido definitivamente por toxicidad severa únicamente con EGS por emesis refractaria (2 participantes) y QTc prolongado con extrasístoles (1 participante). Conclusiones : La eficacia del tratamiento con AM y EGS fue comparable. La administración endovenosa de ambos no produjo efectos adversos inmediatos, aunque sí alteraciones clínicas y laboratoriales usuales.

SUMMARY Objectives : To compare the efficacy and safety of sodium stibogluconate (SS) and meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in a general hospital. Methods: Case-series of 193 patients with CL treated in three clinical trials with MA (n=69) and SS (n=124) during 2001-2010. Both study drugs were administered intravenously at a slow speed at 20 mg Sb5+/kg/day for 20 consecutive days following WHO-PAHO recommendations. Clinical and safety data were gathered from clinical files. Results: Demographic characteristics were similar between the study groups, but the size and number of lesions were higher in the MA group. Efficacy was 76.0% in the MA vs. 68.4% in the SS group (p=0.340) and 55.1% vs. 50.8% (p=0.570) in the per protocol and intention to treat analysis. respectively. Side effects more frequently reported were dysgeusia (37.0%). dizziness (32.0%). headache (36.0%). arthralgia (31.0%) and lymphangitis (21.0%). These first three symptoms as well as elevation of transaminases, leukopenia, thrombocytopenia and prolonged QTc were numerically more frequent in the SS group but without reaching statistical significance. Treatment was stopped definitively for severe toxicity in the SS group due to refractory emesis (two patients) and prolonged QTc (one patient). Conclusions: The efficacy of MA and SS is comparable. The intravenous administration of these compounds did not produce immediate reactions, but it was associated with unusual clinical and laboratory abnormalities.

Leishmaniasis cutánea simuladora de pericondritis

Resumen La leishmaniasis cutánea presenta una clínica muy característica de pápula eritemato-amarillenta con costra central, en regiones expuestas, que los profesionales de la salud podemos identificar y tratar sin necesidad de biopsia. En ocasiones, se presenta con una clínica atípica que puede conducir a un error diagnóstico, con su perpetuación y malestar en el paciente. Presentamos el caso de una mujer de 53 con una placa eritema-to-exudativa por toda la extensión del pabellón auricular izquierdo de varios meses de evolución. Había sido tratada desde el inicio con antibioterapia y corticoides, sin conseguir mejoría y con un claro empeoramiento, al haberse extendido por toda la oreja. Tras la realización de la biopsia, se llegó al diagnóstico de leishmaniasis cutánea erisipeloide. Se procedió a realizar tratamiento dirigido con fluconazol y posteriores infiltraciones de antimoniato de meglumina consiguiendo su completa resolución.

Abstract Cutaneous leishmaniasis presents a very characteristic clinic of erythematous-yellowish papule with central crust, in exposed regions, that we health professionals can identify and treat without the need for a biopsy. Sometimes, it presents with an atypical clinic that can lead to a diagnostic error, with its perpetuation and discomfort in the patient. We present the case of a 53-year-old woman with an erythematous-exudative plaque throughout the extension of the left atrial pavilion of several months of evolution. It had been treated from the start with antiobiotherapy and corticosteroids, without achieving improvement and with a clear worsening, as it had spread throughout the ear. After the biopsy was performed, the diagnosis of erysipeloid cutaneous leishmaniasis was reached. Directed treatment with fluconazole and subsequent infiltrations of meglumine antimoniate were made, achieving its complete resolution.

Alterações eletrocardiográficas em pacientes com Leishmaniose Tegumentar Americana tratados com antimoniato de meglumina: revisão integrativa / Electrocardiographic changes in patients with American tegumentary leishmaniasis treated with meglumine antimoniate: integrative review

Introdução: a Leishmaniose Tegumentar Americana (LTA) é uma infecção zoonótica cujo tratamento é realizado com a droga antimoniato de meglumina (AM). Objetivo: Relatar as alterações eletrocardiográficas decorrentes do uso de AM em pacientes com LTA. Metodologia: foi realizada uma revisão integrativa da literatura por meio das bases de dados BIREME, PUBMED, COCHRANE, SCIELO e literatura cinzenta, usando como estratégia de busca o cruzamento dos seguintes descritores, nos idiomas português e inglês: leishmaniose cutânea, eletrocardiografia, meglumina e toxicidade. Não foi estipulado um intervalo temporal para que um maior número de publicações fosse obtido. Resultados: foram encontrados 134 artigos, desses apenas 09 atenderam aos critérios de inclusão. As principais alterações eletrocardiográficas encontradas durante a terapêutica foram as alterações de repolarização ventricular, com destaque para o prolongamento do intervalo QT corrigido pela frequência cardíaca. Já entre as alterações mais graves em termos de morbimortalidade, destacam-se as arritmias ventriculares complexas, principalmente a Torsade de pointes. Discussão: em todos os artigos selecionados foram encontradas alterações ao eletrocardiograma (ECG) durante o tratamento com AM, sendo recomendado em todos os pacientes, o acompanhamento eletrocardiográfico. Apenas um estudo excluiu as alterações do ECG basal, presença de comorbidades e uso de drogas cardiotóxicas sendo esses possíveis vieses para avaliação da toxicidade cardíaca diretamente provocada pelo antimonial. Conclusão: considerando as alterações na repolarização ventricular e as possíveis arritmias ventriculares em pacientes em tratamento para LTA em uso de AM, o acompanhamento eletrocardiográfico é recomendado durante a terapêutica de todos esses pacientes, sendo útil para prevenção de complicações cardiovasculares importantes.

Introduction: American Tegumentary Leishmaniasis (ATL) is a zoonotic infection whose treatment is carried out with the meglumine antimoniate drug (AM). Objective: To report the electrocardiographic changes resulting from the use of AM in patients with ATL. Methodology: an integrative literature review was carried out using the BIREME, PUBMED, COCHRANE, SCIELO and gray literature databases, using as a search strategy the crossing of the following descriptors, in Portuguese and English: cutaneous leishmaniasis, electrocardiography, meglumine and toxicity. A time interval was not stipulated in order to obtain a greater number of publications. Results: we found 134 articles, of which only 9 met the inclusion criteria. The main electrocardiographic changes found during therapy were changes in ventricular repolarization, with emphasis on the prolongation of the QT interval corrected by heart rate. Already the most serious changes in terms of morbidity and mortality, complex ventricular arrhythmias, especially Torsade de pointes, stand out. Discussion: changes in the electrocardiogram (ECG) were found in all selected articles during treatment with AM, with electrocardiographic monitoring being recommended in all patients. Only one study excluded: changes in the baseline ECG, the presence of comorbidities and / or use of cardiotoxic drugs, these being possible biases to assess cardiac toxicity directly caused by the antimonial. Conclusion: considering the changes in ventricular repolarization and possible ventricular arrhythmias in patients undergoing treatment for ATL using AM, electrocardiographic monitoring is recommended during the therapy of all these patients, being useful for the prevention of important cardiovascular complications.

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration

ABSTRACT: Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p 0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and 1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.

RESUMO: Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p 0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida 1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration / Efeitos do flunixin meglumine, meloxicam e firocoxib na concentração de proteínas da fase aguda após em equinos após castração

Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p<0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and α1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.(AU)

Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p<0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida α1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.(AU)

Estimating direct costs of the treatment for mucosal leishmaniasis in Brazil

Abstract INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.

Pregnancy rates and luteal phase characteristics of bovine embryo recipients treated with flunixin meglumine / Taxas de prenhez e características da fase lútea de receptoras de embriões tratadas com flunixina meglumina em bovinos

The aim of this study was to evaluate the effects of flunixin meglumine administration on pregnancy rates and luteal phase characteristics in bovine embryo recipients at the moment of embryo transfer. In experiment 1, in vitro produced embryos were transferred to 184 females divided as control and treated group (recipients treated with 1.1mg/kg flunixin meglumine). In experiment 2, 22 females were divided as control group; group 2 (animals submitted to a reproductive tract manipulation similar to an embryo transfer on the 7th day after estrous); and group 3 (females submitted to a manipulation and treatment with 1.1mg/kg flunixin meglumine). In experiment 1 no difference was observed between control and treated groups (40.2% and 44.6%, respectively) for pregnancy rates. In experiment 2 no difference was observed on the length of luteal phase between groups, however, animals in group 2 presented lower plasma progesterone concentrations than the control group and group 3. Therefore, we concluded that although the administration of flunixin meglumine at the moment of embryo transfer inhibited the reduction plasma progesterone concentrations, it was not effective in increasing pregnancy rates of bovine recipients.(AU)

O objetivo deste estudo foi avaliar os efeitos da administração de flunixina meglumina sobre as taxas de prenhez e características da fase lútea da receptora no momento da transferência de embriões em bovinos. No experimento 1, embriões produzidos in vitro foram transferidos para 184 fêmeas, divididas em grupos controle e tratado (tratados com 1,1mg/kg de flunixina meglumina). No experimento 2, 22 fêmeas foram divididas em grupo controle (n=7); grupo 2 (n=8; animais submetidos à manipulação do trato reprodutivo semelhante à transferência de embriões no sétimo dia pós-cio); e grupo 3 (n=7; fêmeas submetidas à manipulação e ao tratamento com 1,1mg/kg de flunixina meglumina). No experimento 1, não foi observada diferença nos grupos controle e tratado (40,2% e 44,6%, respectivamente) para as taxas de prenhez. No experimento 2, não houve diferença na extensão da fase lútea entre os grupos, entretanto os animais do grupo 2 apresentaram concentrações plasmáticas de progesterona mais baixas que o grupo controle e o grupo 3. Portanto, conclui-se que a administração de flunixina meglumina no momento da transferência de embriões inibiu a redução das concentrações plasmáticas de progesterona, no entanto não foi eficaz para aumentar as taxas de prenhez de receptoras em bovinos.(AU)

Determination of the content of Gd3+ in gadoteric acid meglumine salt injection by ICP-MS method / 药学实践杂志

Objective To establish a method for determining the content of Gd3+ in gadoteric acid meglumine salt injection. Methods ICP-MS was used. The separation column was a metal chelate column (1-ml Chelating Sepharose column), column temperature was normal temperature. Flow rate was 1 ml/min. Injection volume was 500 μl. Atoms were measured by ICP-MS with a molecular weight of 157 (The molecular weight of Gd was 157). The carrier gas was argon. Results The linear range of Gd3+ mass concentration was 0-500 ng/ml (r=1.000); The precision, stability and repeatability of the sample recovery test were all in accordance with the requirements. Conclusion The method was simple in operation, accurate in results and good in repeatability, which could be used to determine the content of Gd3+ in gadoteric acid meglumine salt injection.

The Improvement Of Betulin-3, 28-Diphosphate Water-Solubility By Complexation With Amines–Meglumine And Xymedon

Objective: To study betulin-3,28-diphosphate (BDP) water solubility improved by forming salt complexes with hydrophilic amino alcohols: meglumine as acidosis corrector and xymedon as the water-soluble antioxidant. Methods: We used 13C-, 31P-NMR, UV-spectroscopy and potentiometric titration to study the BDP-amine salt complexes formation and their solubility using HPLC-analysis. Results: The participation of xymedon in the proton transfer reaction with BDP in aqueous solutions was confirmed by the bathochromic shift of the carbonyl band from 299.1 nm to 304.2 nm, and by a hyperchromic effect (molar extinction ε from 8508 to 10 441 l·mol-1·cm-1) in UV-spectra. BDP complexation with meglumine was estimated by UV-spectral molar ratio method at 256 nm. Molar ratio of BDP-amine complexes (1:4) was proved by 31P-NMR. The chemical shift of phosphorus at C-3 atom of BDP (δ =-0.58 ppm) changed to+3.39 ppm, and at C-28 atom (δ =+0.28 ppm)–to+4.60 ppm. BDP solubility increased 100-600 fold according to HPLC-analysis. Conclusion: BDP interaction with amine in an aqueous solution was shown to proceed via a proton transfer due to relatively weak forces such as London forces, hydrogen bonding, electrostatic and hydrophobic interactions. In general, the formation of BDP salt complexes with amines in solution determines BDP water solubility. Water-soluble BDP enables to develop hydrophilic dosage forms.

American tegumentary leishmaniasis: severe side effects of pentavalent antimonial in a patient with chronic renal failure

Abstract: Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

Lesiones verrucosas en la cara de una niña preescolar / Verrucous lesions on the face of a preschool girl

La leishmaniasis cutánea es una enfermedad parasitaria granulomatosa crónica que se transmite por la picadura de flebótomos infectados, esta patología afecta a todos los grupos etarios y los menores de 12 años constituyen únicamente el 10%, las manifestaciones clínicas dependerán de factores como el estado inmune y la especie de Leishmania, la forma clínica de leishmaniasis cutánea representa el 99% en los pacientes pediátricos siendo así la más frecuente, el diagnóstico se basa en criterios clínicos, epidemiológicos y de laboratorio. El tratamiento en la edad pediátrica puede hacerse con antimoniato de meglumina con buena respuesta como en los casos que presentamos a continuación

Cutaneous leishmaniasis is a chronic granulomatous parasitic disease that is transmitted by the bite of infected sandflies, this pathology affects all age groups and those under 12 years constitute only 10%, the clinical manifestations depend on factors such as the immune status and the species of leishmania, the clinical form of cutaneous leishmaniasis represents 99% in pediatric patients being the most frequent, the diagnosis is based on clinical, epidemiological and laboratory criteria. Treatment in the pediatric age can be done with meglumineantimonate with good response as in the cases presented below.

The efficacy and safety of diterpene ginkgolides meglumine injection in stroke:a Meta-analysis / 药学实践杂志

Objective Diterpene ginkgolides meglumine injection (DGMI) is widely used in patients with stroke, but its efficacy and safety are not consistent.We performed a Meta-analysis to comprehensively evaluate the efficacy and safety of DG-MI in acute ischemic stroke and recovered stroke.Methods The wanfang, VIP, CNKI and PubMed were searched, the randomized controlled trials (RCTs) were enrolled.Data collection and quality evaluation of the included RCTs were performed according to Cochrane systematic evaluation method.Meta-analysis was performed by using Stata software.Results 9RCTs involving 1 129subjects were included with 706subjects in DGMI treatment group and 423subjects in control group. (1) For acute ischemic stroke, DGMI group had superior effective rate compared to conventional therapy group (RR=1.19, 95％CI:1.09, 1.31, P＜0.000 1), improvement of neurologic impairments (SMD=3.23, 95％CI:2.87, 3.60, P＜0.000 1) and improvement of living quality (SMD=3.23, 95％CI:2.87, 3.60, P＜0.000 1). (2) For recovered stroke, DGMI group had better effective rate than Shuxuening injection group (RR=1.17, 95％CI:1.05, 1.30, P＜0.05) and improvement of neurologic impairments (SMD=-0.69, 95％CI:-0.88, -0.49, P＜0.000 1).There was no significant difference in adverse events between DGMI and control groups (P＞0.05).Conclusion DGMI had superior efficacy over control group for both acute ischemic stroke and recovered stroke.There was no significant difference in adverse events between these two groups.However, we still need better quality RCTs to confirm these results.

Effects of ginkgo diterpene lactone meglumine on learning and memory in old mice and its mecha-nisms / 中华行为医学与脑科学杂志

Objective To study the effects of diterpene ginkgolides meglumine injection ( DGMI) on memory impairment, activation of microglia and astrocytes and inflammatory cytokines in aged mice. Methods Twenty aged mice (22 months old) were randomly divided into two groups:aged mouse group(n=10) and DGMI group(n=10). Another 10 mice (2 months old) were selected as young mouse control group. The mice in DGMI group were received 5 mg/kg DGMI per day by tail vain injection for 4 weeks. The mice in the other two groups were received the same amount normal saline for 4 weeks. The Morris water maze was used to evaluate the function of spacial learning and memory after administration of drugs. The ex-pression of CD11b,GFAP,IL-1β,IL-6,TNF-α and NFκB in mice brain hippocampus were detected by West-ern blot. Results (1) The escape latency time of aged mouse group was significantly longer than that of young mouse control group from the 2nd day to the 7th day(P<0. 01). The times of platform crossing,time and distance in target quadrant of aged mouse group were significantly shorter than those of young mouse group (all P<0. 01). Compared with aged mouse group,DGMI significantly reduced the escape latency time of DGMI group (P<0. 01). DGMI increased the times of platform crossing,time and distance in target quad-rant of aged mouse group (P<0. 01). (2) The expressions of CD11b,GFAP in young mouse control group, aged mouse group and DGMI group were as follows respectively:CD11b:(1. 036±0. 023),(1. 757±0. 046), (1. 214±0. 024);GFAP:(1. 022±0. 071),(1. 344±0. 021),(1. 086±0. 073). DGMI reduced the expres-sion of CD11b and GFAP in hippocampus compared with aged mouse group ( t=5. 556,P<0. 01;t=5. 484, P<0. 01). (3) The expressions of IL-1β,IL-6,TNF-α and NFκB in young mouse control group,aged mouse group and DGMI group were as follows respectively:IL-1β:( 1. 003 ± 0. 057),( 2. 062± 0. 105),( 1. 182± 0. 084);IL-6:(1. 018±0. 024),(1. 583± 0. 052),( 1. 152± 0. 031); TNF-α:( 1. 021± 0. 054),(1. 449± 0. 053),(1. 211±0. 036);p-NFκB:(1. 052±0. 034),(1. 782± 0. 113),( 1. 158± 0. 066). DGMI reduced the expression of p-NFκB(t=6. 547,P<0. 01) and pro-inflammatory cytokines including IL-1β(t=8. 513,P<0. 01),IL-6(t=3. 421,P<0. 01) and TNF-α( t=5. 562,P<0. 01) in hippocampus compared with aged mouse group. Conclusion DGMI can improve the ability of learning and memory in aged mice. The mecha-nism may be related with inhibiting activity of microgliosis,astrocytosis,NFκB and neuroinflammaton.

Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)

Successful treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate: A case series

Abstract Cutaneous leishmaniasis (CL) is a high-morbidity, vector-borne disease endemic to Colombia. Unlike conventional systemic antileishmanial therapy, intralesional meglumine antimoniate administration has fewer adverse effects and can be as effective and safe. We describe 12 patients treated with intralesional meglumine antimoniate: seven with primary and five with recurrent lesions. The majority (11/12) met all cure criteria after 1-7 sessions of meglumine antimoniate administration (1-5 mL). Adverse effects comprised mainly of local pain and edema. Intralesional meglumine antimoniate administration could be an excellent alternative treatment for uncomplicated CL; however, controlled clinical trials are needed to test the efficacy and safety thereof.

Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary leishmaniasis acquired in different Brazilian regions

Abstract INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.

Mucosal leishmaniasis: the experience of a Brazilian referral center

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.

Towards a standard protocol for antimony intralesional infiltration technique for cutaneous leishmaniasis treatment

BACKGROUND Despite its recognised toxicity, antimonial therapy continues to be the first-line drug for cutaneous leishmaniasis (CL) treatment. Intralesional administration of meglumine antimoniate (MA) represents an alternative that could reduce the systemic absorption of the drug and its side effects. OBJECTIVES This study aims to validate the standard operational procedure (SOP) for the intralesional infiltration of MA for CL therapy as the first step before the assessment of efficacy and safety related to the procedure. METHODS The SOP was created based on 21 trials retrieved from the literature, direct monitoring of the procedure and consultation with experts. This script was submitted to a formal computer-aided inspection to identify readability, clarity, omission, redundancy and unnecessary information (content validation). For criterion and construct validations, the influence of critical condition changes (compliance with the instructions and professional experience) on outcome conformity (saturation status achievement), tolerability (pain referred) and safety (bleeding) were assessed. FINDINGS The median procedure length was 12 minutes and in 72% of them, patients classified the pain as mild. The bleeding was also classified as mild in 96.6% of the procedures. Full compliance with the SOP was observed in 66% of infiltrations. Despite this, in 100% of the inspected procedures, lesion saturation was observed at the end of infiltration, which means that it tolerates some degree of modification in its execution (robustness) without prejudice to the result. CONCLUSIONS The procedure is reproducible and can be used by professionals without previous training with high success and safety rates.

Electronic cleaning of intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning / 重庆医学

Objective To study the feasibility of applying electronic cleaning to intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning.Methods Twenty-four volunteers had fine effect of intestinal contents tagging by diatrizoate meglumine,good colorectal distension effect,fine image quality of dual-energy fusion colorectal images,and with informed consents were enrolled in this study.The single-source dual-energy CT colonography with sequential acquisitions and volume scanning was performed with an Acquilion ONE 320 row CT scanner,tube voltage 135 kVp/80 kVp.The intestinal contents conducted the dual-energy electronic cleaned based on decomposition of intestinal contents tagging by diatrizoate meglumine,soft tissue and air.The intestinal contents in one segment of intestinal lumen being 100％ electronically cleaned served as the basic standard,the electronic cleaning effects were divided into the 5 grades:excellent,good,moderate,fair and poor;and grade 1-3 were effective fecal electronic cleaning.Results The grade 1,2,3,4,5 of electronic cleaning effect for solid as the main intestinal contents were 22.2％,53.3％,17.8％,6.7％ and 0％ respectively;and which of electronic cleaning effect for liquid as the main intestinal contents were 47.5％,47.5％,5.0％,0％ and 0％ respectively.The together total effective electronic cleaning of intestinal contents was 97.9％ and the electronic cleaning effect was good.Conclusion Electronic cleaning could be used in the intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning.

Pedometria e acompanhamento bioquímico no pós-operatório de bovinos Nelore com onfalopatias / Pedometer and biochemistry monitoring on postoperative from Nelore cattle with umbilical diseases

A analgesia pós-operatória em bovinos, por vezes, é negligenciada, frequentemente por falta de métodos quantitativos para seu diagnóstico e dimensionamento. Os objetivos deste trabalho foram: avaliar a pedometria e o acompanhamento bioquímico no pós-operatório de bovinos Nelore com onfalopatias e comparar a eficiência anti-inflamatória e analgésica entre diferentes doses de flunixin meglumine e meloxicam nesses animais. Foram utilizados 24 bovinos; deste total, 18 animais foram submetidos a laparotomia para tratamento das onfalopatias e, posteriormente, divididos em três grupos de animais: G1, que recebeu 1,1mg/kg flunixin; G2, 2,2mg/kg flunixin; G3, 0,5mg/kg meloxicam. A via de eleição para os tratamentos foi a IM, uma vez ao dia, totalizando seis aplicações. Outros seis bovinos saudáveis compuseram o grupo controle (GC). As coletas do sangue total para mensuração do cortisol plasmático foram realizadas antes e depois da cirurgia, assim como a leitura do pedômetro e o exame clínico. As concentrações plasmáticas de cortisol diferiram apenas no M0, entre o GC e os grupos tratados. O flunixin meglumine em diferentes doses e o meloxicam foram equivalentes no tratamento da dor pós-operatória e no efeito anti-inflamatório em bovinos submetidos à laparotomia para tratamento das onfalopatias.(AU)

Postoperative analgesia in cattle is sometimes overlooked, frequently due to the lack of quantitative methods for diagnosis and measurement. The objectives of this study were: to analyze the pedometric and biochemistry alterations of postoperative period in Nelore bovines with umbilical diseases; compare the anti-inflammatory and analgesic efficiency between different doses of flunixin meglumine and meloxicam in the postoperative of umbilical diseases in these animals. Twenty four bovines were used. From this total, 18 animals were submitted to laparotomy for treatment of umbilical diseases and subsequently divided into three groups of animals: G1, which received 1.1mg/kg flunixin, G2 2.2mg/kg flunixin, G3 0.5mg/kg meloxicam. Six other healthy cattle were allocated to the control group (CG). Total blood samples for plasma cortisol clinical examination was performed on standardizer times. Plasma cortisol concentrations differed only in the M0 between GC and treated groups. Flunixin meglumine in different doses and meloxicam were equivalent in the treatment of postoperative pain and anti-inflammatory effect in cattle submitted to laparotomy for the treatment of umbilical diseases.(AU)