Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report / Tiosulfato de sodio y pamidronato para el tratamiento de calcifilaxis: reporte de caso

Abstract Introduction: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. Clinical Case: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. Treatment and Outcome: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. Conclusion: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

Resumen: Introducción: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. Caso Clínico: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. Tratamiento y resultado: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. Conclusión: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

Exercise Training Attenuates Sympathetic Activity and Improves Morphometry of Splenic Arterioles in Spontaneously Hipertensive Rats / Treinamento Físico Atenua a Atividade Simpática e Melhora a Morfometria das Arteríolas Esplênicas em Ratos Espontaneamente Hipertensos

Abstract Background: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. Objective: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Methods: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. Results: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). Conclusions: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Resumo Fundamento: Alterações na estrutura dos vasos de resistência contribuem para elevar a resistência vascular sistêmica na hipertensão, estando ligadas à hiperatividade simpática e lesões em órgãos-alvo. Objetivo: Avaliar os efeitos do treinamento físico nos parâmetros hemodinâmicos e autônomos, assim como as lesões arteriolares esplênica em ratos machos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Métodos: Ratos normotensos sedentários (WKYS) e treinados (WKYT), e ratos hipertensos sedentários (SHRS) e treinados (SHRT) foram incluídos neste estudo. Após nove semanas de aplicação do protocolo experimental (treinamento de natação ou controle sedentário), registraram-se a pressão arterial (PA) e a frequência cardíaca (FC) dos ratos em movimento livre. Avaliamos o controle autônomo do coração através de bloqueio autônomo simpático e vagal. Análises morfométricas das arteríolas esplênicas foram realizadas. Adotou-se o nível de significado estatístico de p < 0,05. Resultados: Observou-se bradicardia de repouso nos dois grupos treinados (WKYT: 328,0 ± 7,3 bpm; SHRT: 337,0 ± 5,2 bpm) em comparação aos seus respectivos grupos sedentários (WKYS: 353,2 ± 8,5 bpm; SHRS: 412,1 ± 10,4 bpm; p < 0,001). O treinamento físico atenuou a PA média apenas no grupo SHRT (125,9 ± 6,2 mmHg vs. 182,5 ± 4,2 mmHg no SHRS; p < 0,001). O grupo WKYT mostrou maior efeito vagal (∆FC: 79,0 ± 2,3 bpm) em comparação ao grupo WKYS (∆FC: 67,4 ± 1,7 bpm; p < 0,05). Exercício crônico diminuiu os efeitos simpáticos em SHRT (∆FC: -62.8 ± 2.8 bpm) em comparação a SHRS (∆FC: -99,8 ± 9,2 bpm; p = 0,005). A espessura da parede das arteríolas esplênicas nos SHR foi reduzida pelo treinamento (332,1 ± 16,0 µm2 nos SHRT vs. 502,7 ± 36,3 µm2 nos SHRS; p < 0,05). Conclusões: O treinamento físico atenua a atividade simpática e a PA em SHR, o que pode contribuir para melhorar a morfologia das arteríolas esplênicas.

Endothelin-1 expression in pulmonary hypertensive chickens by hypoxia / Expresión de Endotelina-1 en pollos con hipertensión arterial pulmonar por hipoxia hipobárica

ABSTRACT Objective. To determine the effect of hypobaric hypoxia exposition in pulmonary arterioles expression of endothelin-1 (ET-1). Materials and methods. Two groups of commercial broiler chickens were used: one of them were raised at 2638 (hypobaric hypoxia) and the other one at 300 m (relative normoxia) above sea level. Incidence of pulmonary hypertension (PH) was evaluated by calculating the cardiac mass index values and ET-1 protein expression was established in pulmonary arterioles by immunohistochemistry and morphometry. Results . ET-1 expression was higher in arterioles of animals exposed to hypoxia as compared to the low altitude exposed broilers (p<0.01). Arterioles from pulmonary hypertensive chickens (PHC) showed ET-1 higher expression than arterioles from healthy chickens (non-hypertensive, NHC) at low altitude, those exposed to hypobaric hypoxia (p<0.01). 53% of chickens subjected to altitude conditions developed pulmonary hypertension. Under normoxia, no chickens developed that pathology. Conclusions. Quantitative characteristics and sites of ET-1 expression in the lungs are important in the understanding of PH pathogenesis in broilers and the adapting mechanisms to hypobaric hypoxia, as to design new pharmacological approaches. This is a first approach which accounts for the abovementioned features in broilers subjected to natural conditions of normoxia and hypobaric hypoxia.

RESUMEN Objetivo. Determinar el efecto de la exposición a hipoxia hipobárica sobre la expresión de Endotelina-1 en arteriolash pulmonares. Material y métodos. Se utilizaron 2 grupos de pollos de engorde de una estirpe comercial: uno de ellos criados a 2638 y el otro, a 300 m de altitud. La incidencia de HAP se evaluó según los valores del índice de masa cardiaca y se compararon los niveles de expresión de la proteína ET-1 en arteriolas pulmonares de pollos de engorde sanos y enfermos por HAP mediante inmunohistoquímica y morfometría. Resultados. La expresión de la proteína ET-1 fue mayor en las arteriolas de los pollos expuestos a hipoxia hipobárica que en los criados bajo condiciones de normoxia relativa (p<0.01). Los animales enfermos por HAP presentaron mayor expresión de la proteína ET-1 en las arteriolas pulmonares que los animales sanos ubicados en las dos altitudes (p<0.01). 53% de los animales desarrollaron hipertensión pulmonar y ninguno de los mantenidos en normoxia lo hicieron. Conclusiones. El conocimiento de las características cuantitativas y lo sitios de expresión de la ET-1 son elementos importantes para entender aún más la patogenia de la HAP y el diseño de fármacos para su control. Este estudio constituye la primera aproximación cuantitativa relacionada con la expresión de ET-1 en pollos de engorde con HAP de origen hipóxico no inducida.

The histological analysis of the glenohumeral "critical zone" / Análisis histológico de la "zona crítica" glenohumeral

The arterial integrity of the "critical zone" of the rotator cuff has led to much uncertainty regarding rotator cuff tendinopathy. As the region of the supraspinatus tendon is the most common area affected by impingement, its central aspect is situated approximately 10 mm from the insertion at the greater humeral tubercle. Although many studies have investigated the vascularity of the "critical zone", there still appears to be lack of consensus regarding its extent. Through the employment of gross dissection and standard histology analysis of twenty-five adult bilateral cadaveric scapulo-humeral regions (n = 50), this study aimed to quantify the degree of vascularity, or lack thereof, within the "critical zone" by evaluating its relative morphometric features. The demographic representation of the sample was also considered. Results: i) Mean diameter of arteriole lumen: 91.6±75.2 µm; ii) Mean diameter of entire arteriole: 119.8±87.1 µm; iii) Mean arteriole wall thickness: 15.1±9.5 µm; iv) Mean area occupied by an arteriole: 20644.4±3358.0 µm2; v) Mean number of arterioles within "critical zone": 14.6±8.7. All tissue samples displayed a scarce distribution of arterioles along the musculo-tendinous junction relative to the "critical zone". A directly proportional relationship between the morphometric parameters was indicated by positive strong correlations and accompanying statistically significant P values. As 66 % of the number of arterioles within the "critical zone" were distributed between the minimum value and the upper quartile, it was postulated to be hypovascular, therefore confirming the findings of previous studies.

La integridad arterial de la "zona crítica" del manguito rotador ha dado lugar a una gran incertidumbre con respecto a la tendinitis del mismo. A medida que la región del tendón del músculo supraespinoso sea el área más común afectada por el impacto, su aspecto central estará situado aproximadamente a 10 mm desde la inserción en el tubérculo mayor del húmero. Aunque muchos estudios han investigado la vascularización de la "zona crítica", aún parece existir falta de consenso en cuanto a su extensión. A través de la disección macroscópica y análisis de la histología normal de ambas regiones escápulo-humerales, se realizó en 25 cadáveres adultos (n = 50), este estudio que tuvo como objetivo cuantificar el grado de vascularización, o su ausencia, dentro de la "zona crítica" mediante la evaluación de su características morfométricas. También se consideró la representación demográfica de la muestra. Resultados: i) La media de diámetro de lumen de las arteriolas: 91,6 ± 75.2 µm; ii) El diámetro medio de la totalidad de las arteriolas: 119,8 ± 87.1 µm; iii) la media del espesor de la pared de las arteriolas: 15,1 ± 9.5µm; iv) La media de la zona ocupada por una arteriola: 20.644,4 ± 3358.0 µm2; v) La media de las arteriolas dentro de la "zona crítica": 14,6 ± 8,7. Todas las muestras de tejidos tenían una escasa distribución de las arteriolas a lo largo de la unión músculo-tendinosa con relación a la "zona crítica". Una relación directamente proporcional entre los parámetros morfométricos indica fuertes correlaciones positivas y junto a valores de P estadísticamente significativos. Como el 66 % de las arteriolas dentro de la "zona crítica" se distribuyeron entre el valor de cuartil mínimo y superior, se postuló como hipovascular, por lo tanto confirma los resultados de estudios anteriores.

Efeito da poluição atmosférica urbana da cidade de São Paulo nas células sangüíneas e no sistema cardiopulmonar: estudo morfo-funcional em camundongos in vivo / Effect of urbain air pollution of Sao Paulo city in the blood and cardiopulmonary system: a morpho-functional study in mice in vivo

Objetivo: checar se poluentes do ar urbano de São Paulo induzem alterações sangüíneas e cardiopulmonares. MM: camundongos Balb/c foram expostos por 7, 14, 21, 30 e 45 dias em 3 câmaras: Limpa (controle), Intermediária (seletiva ao PM) e Suja (ar externo). Após exposição, os animais foram ventilados (FlexiVent) e coletados dados de mecânica pulmonar, sangue, coração e pulmão. Foram registrados PM, CO, SO2 e NO2 diários. Resultados: aos 21 e 45 dias coincidentes com picos de poluição houve aumento da resistência de via aérea (45d p=0,012), leucocitose (21d p < 0,001 e 45d p=0,039) e vasoconstricção pulmonar (21d p=0,034) nos animais da Câmara Suja, sem alteração de coronárias. Nenhum poluente excedeu limites de qualidade de ar.

Objective: verify if air pollution of São Paulo city induces alterations in blood and cardiopulmonary systems. MM: Balb/c mice were exposed during 7, 14, 21, 30 and 45 days to 3 chambers: Clean (control), Intermediate (PM only) and Dirty (external air). After exposure, animals were ventilated (FlexiVent) and collected lung mechanics data and blood, heart and lung. PM, CO, SO2 e NO2 were measured daily. Results: on day 21 and 45, coincidently to peak of pollutions, there was proximal airway resistance increase (45d p=0.012), leukocytosis (21d p < 0.001 and 45d p=0.039) and vasoconstriction of peribronchiolar arterioles (21d p=0.034) in animals of Dirty Chamber with no alterations of coronaries. Neither pollutants exceeded the standard limits.