Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, HSL and HMG-CoA reductase in hyperlipidemia rabbits / 针灸推拿医学（英文版）

Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Importância da biópsia hepática no diagnóstico da deficiência de lipase ácida lisossomal: relato de caso / Importance of liver biopsy in the diagnosis of lysosomal acid lipase deficiency: a case report

RESUMO Objetivo: Descrever a doença de depósito de ésteres de colesterol (DDEC) e a importância da biópsia hepática na realização do diagnóstico. Descrição do caso: Paciente feminina, dois anos e dez meses de idade, com queixa de aumento do volume abdominal secundário à hepatomegalia há quatro meses. Ultrassonografia abdominal demonstrou hepatomegalia e esteatose hepática. Exames laboratoriais mostraram aumento de enzimas hepáticas e dislipidemia. A biópsia hepática foi compatível com DDEC. Comentários: Embora a medida da atividade enzimática seja o padrão-ouro para o diagnóstico de DDEC, a biópsia hepática é muito útil na investigação de casos suspeitos, particularmente quando há outros diagnósticos diferenciais a serem considerados.

ABSTRACT Objective: To describe a case of cholesteryl ester storage disease (CESD) and discuss the importance of liver biopsy for diagnosis. Case description: A female patient, aged two years and ten months, presented with an increased abdominal volume following hepatomegaly for four months. Abdominal ultrasound demonstrated hepatomegaly and hepatic steatosis. Laboratory tests showed elevated liver serum enzymes and dyslipidemia. Liver biopsy was consistent with CESD. Comments: Although measuring enzyme activity is the gold standard for CESD diagnosis, liver biopsy is very helpful when investigating suspected cases of CESD, particularly upon other differential diagnoses to be considered.

Detección de la mutación E8SJM en el gen LIPA, por PCR en tiempo real, para la investigación de la enfermedad por almacenamiento de ésteres de colesterol / Detection of the E8SJM mutation in the LIPA gene, by real-time PCR, for the investigation of cholesteryl ester storage disease

Introducción: La enfermedad por Almacenamiento de Ésteres de Colesterol (CESD; Cholesteryl Ester Storage Disease) es una enfermedad de depósito lisosomal, su presentación es bastante variable y su diagnóstico constituye un desafío. Además, existe un número de anomalías observadas en los pacientes con CESD que se sobreponen a diagnósticos más comunes, siendo probable que sea subdiagnosticada. La mayoría de pacientes relatados hasta el momento son portadores de la mutación E8SJM en el gen LIPA. En este sentido, el auxilio en el diagnóstico es fundamental pues existen opciones de terapia en desarrollo. Diseño: Estudio observacional. Objetivo: Estandarizar la técnica de PCR en tiempo real para la detección de la mutación más frecuente, E8SJM, en muestras de sangre periférica y de biopsia hepática para el auxilio diagnóstico de CESD y futuros estudios de prevalencia de la mutación. Institución: Centro de Terapia Génica del Hospital de Clínicas de Porto Alegre (HCPA), Brasil. Material biológico: Muestras de ADN extraídas de sangre periférica y tejido hepático parafinado. Principales medidas de resultados: Presencia/Ausencia de la mutación E8SJM. Resultados: Se estandarizó la reacción de PCR en tiempo real, la mutación fue detectada correctamente y posteriormente validada por secuenciación de Sanger. La mutación fue analizada en 137 muestras y encontrada en apenas una paciente que ingresó al Servicio de Genética Médica del HCPA con diagnóstico clínico y bioquímico de CESD/Wolman. Conclusiones: La técnica de PCR en tiempo real es ideal para la detección rápida y en gran escala de la mutación frecuente asociada a CESD.

Introduction: Cholesteryl Ester Storage Disease (CESD) is a lysosomal storage disorder, its presentation is highly variable and its diagnosis challenging. In addition, there are several abnormalities observed in patients with CESD who overlap with more common diagnoses and are likely to be underdiagnosed. Most patients reported to date are carriers of the E8SJM mutation in the LIPA gene. In this sense, diagnostic assistance is essential because there are options for therapy in development, as well as mutation prevalence studies. Design: Observational research. Objective: To standardize the real-time PCR technique for the detection of the most frequent mutation, E8SJM, in peripheral blood and liver biopsy specimens for the diagnosis of CESD and future mutation prevalence studies. Institution: Center of Gene Therapy of the Hospital de Clinicas de Porto Alegre (HCPA), Brazil. Biological material: DNA samples extracted from peripheral blood and paraffinembedded liver tissue. Main outcome measures: Presence / Absence of E8SJM mutation. Results: The PCR reaction was standardized in real time; the mutation was correctly detected and validated by Sanger sequencing. The mutation was analyzed in 137 samples and found in only one patient who entered the Medical Genetics Service of the HCPA with clinical and biochemical diagnosis of CESD/Wolman. Conclusions: The real-time PCR technique is ideal for rapid and large-scale detection of the frequent CESD-associated mutation.