Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics / 中国中药杂志

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

Role of ACE and ACE-2 in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart

Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff's apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.

A case of intramural coronary amyloidosis associated with hemodialysis

Dialysis-related amyloidosis predominantly occurs in osteo-articular structures and dialysis-related amyloid (DRA) substances also deposit in extra-articular tissues. Clinical manifestations of DRA include odynophagia, gastrointestinal hemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction, and subcutaneous tumors. The pathological characteristics of DRA in the heart of hemodialysis patients have rarely been reported. We report the case of a 73-year-old female with a history of cerebral palsy and end-stage renal disease status post two failed renal transplants who had been on hemodialysis for 30 years. The patient was admitted with the working diagnosis of pneumonia. An echocardiography showed markedly reduced biventricular function manifested by low blood pressure with systolic in the 70s and elevated pulmonary artery pressure of 45 mmHg, which did not respond to therapy. Following her demise, the autopsy revealed bilateral pulmonary edema and pleural effusions. There was cardiac amyloid deposition exclusively in the coronary arteries but not in the perimyocytic interstitium. Amyloids were also found in pulmonary and intrarenal arteries and the colon wall. Previous case reports showed that beta 2-microglobulin amyloid deposits in various visceral organs but less frequently in the atrial and/or the ventricular myocardium. In the present case, amyloids in the heart were present in the intramural coronary arteries causing myocardial ischemia and infarction, which was the immediate cause of death.

Severe Mesenteric Hemorrhagic Infarction by Superior Mesenteric Arterial Occlusion in a Patient with Buerger's Disease / 대한소화기학회지

No abstract available.

Alterações histopatológicas em placentas humanas relacionadas às síndromes hipertensivas / Histopathological changes in human placentas related to hypertensive disorders

OBJETIVO: determinar a prevalência de alterações histopatológicas em placentas humanas, relacionadas às síndromes hipertensivas. MÉTODOS: estudo de corte transversal, que comparou as alterações histopatológicas identificadas em 43 placentas oriundas de gestantes do grupo de hipertensas (GrHip) com as de 33 placentas de gestantes do grupo de normotensas (GrNor). Foram analisados o peso, volume e ocorrência macro e microscópica de infartos, coágulos, hematomas, aterose (obliteração parcial, espessamento de camadas e presença de vasos hialinizados) e alterações de Tenney-Parker (ausentes, discretas e proeminentes), bem como a localização de infartos e coágulos (central, periférico ou associação de ambos). Para a análise estatística foram usados os testes do χ2 e t de Student, bem como médias, desvios padrões e percentuais. Considerou-se como significante um p<0,05. RESULTADOS: o estudo macroscópico revelou que as placentas do GrHip, se comparadas às do GrNor, apresentaram menor peso (461,1 versus 572,1 g) e volume (437,4 versus 542,0 cm³) e percentuais aumentados de infartos (51,2 versus 45,5 por cento; p<0,05; OR=1,15) e de coágulos (51,2 versus 15,1 por cento; p<0,05; OR=5,4). Nos GrHip e GrNor, os infartos microscópicos ocorreram em 83,7 e 45,5 por cento; p<0,05; OR=4,3, respectivamente. A aterose e as alterações de Tenney-Parker associaram-se estatisticamente às síndromes hipertensivas (p<0,05). CONCLUSÕES: os dados obtidos permitem associar menor peso e volume placentário, maior percentual de infartos macro e microscópicos, coágulos, aterose e alterações de Tenney-Parker às placentas relacionadas com gestações que cursaram com síndromes hipertensivas.

PURPOSE: to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. METHODS: a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr), with the ones from 33 placentae from normotensive pregnant women (NorPr). The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization) and Tenney-Parker changes (absent, discreet and prominent), as well as the locating of infarctions and clots (central, peripheral or the association of both) have been analyzed. The χ2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. RESULTS: the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g) and volume (437.4 versus 542.0 cm³), higher infarction (51.2 versus 45.5 percent; p<0.05: OR=1.15) and clots (51.2 versus 15.1 percent; p<0.05; OR=5.4) ratios, as compared to the NorPr's. In the HypPr and NorPr, microscopic clots have occurred in 83.7 versus 45.5 percent (p<0.05; OR=4.3), respectively. Atherosis and Tenney-Parker changes have been statistically associated to the hypertensive syndromes (p<0.05). CONCLUSIONS: the obtained data allow us to associate lower placentary weight and volume, higher ratio of macro and microscopic infarction, clots, atherosis and Tenney-Parker changes to placentae of gestations occurring with hypertensive syndromes.

Study of placenta in sickle cell disorders.

Remarkable changes are seen on gross and microscopic examination of placenta of patients with sickle cell disorders, hence the present study was undertaken to find out the pathological changes seen in the placenta of sickle cell disorder patients, as compared to control and to study the effect of maternal sickling on the fetus. It includes total 73 cases, of which 10 were of control group and 63 were from patients with sickle cell disorders, which included 47 sickle cell trait (AS) and 16 sickle cell disease (SS) patients. In group II, 9 (14.28%) patients with SS pattern developed complications during pregnancy, in the form of vaso-occlusive and hemolytic crises. Pregnancy induced hypertension was seen in 4 (25%) out of 16 SS and 11 (23.40%) of the 47 AS patients. Urinary tract infection (UTI) was seen in 6 (37.5%) out of 16 SS and 8 (17.02%) out of 47 AS patients. Placentae in sickle cell disorders showed pathological changes in the form of infarction, calcification, sickled red blood cells and hemorrhage in intervillous spaces, increased syncytial knots, fibrinoid necrosis, stromal fibrosis, hyalinised villi and compensatory proliferation of trophoblastic cells.

Síndromes dolorosas em diabéticos por comprometimento de musculatura esquelética / Painful syndromes in diabetic patients due to skeletal muscle injuries / Painful syndromes in diabetic patients due to skeletal muscle injuries

Em diabéticos, síndromes dolorosas devidas o comprometimento do músculo esquelético sem neuropatia são complicações raras. Neste relato são apresentados dois casos: Caso 1 (piomiosite em panturrilhas) e Caso 2 (infarto muscular em coxa), sendo comentadas as características clínicas e os procedimentos diagnósticos. É necessário um alto índice de suspeita, uma vez que o tratamento de ambas difere significativamente. Além disso, o diagnóstico pode ser inicialmente confundido com tromboflebite, rabdomiólise ou neoplasia, retardando o tratamento correto. O atraso no tratamento da piomiosite com antibiótico e em alguns casos com cirurgia, pode evoluir para infecção sistêmica e até óbito, enquanto o infarto muscular requer apenas repouso e analgesia. Exames de imagem e de laboratório são úteis no diagnóstico diferencial, porém pode haver superposição dos achados. É enfatizada a importância de incluir estas doenças no diagnóstico diferencial de síndromes dolorosas do membro inferior em diabéticos.

Progressive painful syndromes due to skeletal muscle injuries rather than diabetic neuropathy are unusual complications of diabetes mellitus (DM). Two clinical cases are presented: Case 1 (pyomyositis: leg location) and Case 2 (muscle infarction: thigh location). Discussion on how to proceed the diagnosis based on clinical features are included as it is critical for early and proper treatment since approaches highly differ in the two situations. These complications can mimic thrombophlebitis, rabdomyolises or a neoplasm, therefore the diagnosis of a diabetes-related disorder may be overlooked. If pyomyositis is not correctly treated with antibiotics and in some cases with surgery, systemic infection and even death may occur, whereas muscle infarction only requires rest and analgesia. Image and laboratorial investigations can be of help to differentiate these syndromes, although some findings can overlap. Thus, the present report emphasizes the importance to include these diseases when limb painful syndromes are to be investigated in a diabetic patient.

Histopathological evaluation of placentas in IUGR pregnancies.

Gross and microscopic examination was conducted on one hundred placentas. These included twenty five normal controls and seventy five from intrauterine growth retardation (IUGR) pregnancies. Weight of the placentas from IUGR pregnancies were less than those of normal placentas. The incidence of infarction, intervillous fibrin deposition were much higher in IUGR placentas on gross examination. Highly significant increase in the incidence of infarction, intervillous fibrin deposition, stromal fibrosis and syncytial knotting were found in IUGR placentas compared to full term normal placentas on microscopic examination. The incidence of basement membrane thickening and cytotrophoblastic hyperplasis were also higher in IUGR placentas. All the major histologic findings pointed towards reduced blood flow to the placentas resulting in the restriction of blood flow to fetus. The information obtained from their examination can be a useful adjunct in planning and management of future pregnancies.

Distribución de acuerdo al sexo, grupo etáreo, tasa de mortalidad, tiempo y causa de hospitalización de los pacientes ingresados a la Unidad de Cuidados Intensivos del Hospital Pérez de León de Petare, Caracas durante los años 1992-1997 / Distribution by sex, age group, time, cause of hospitaliza, and mortality rate of the patients admitted in the Intensive Care Unit (ICU)

Se realizó un estudio retrospectivo, de corte transversal entre los años 1992-1997, con la finalidad de investigar las distribución de acuerdo al sexo, grupo etáreo, tiempo (en horas), motivo de ingreso y tasa de mortalidad, de los pacientes hospitalizados en la Unidad de Cuidados Intensivos (UCI) del Hopital Pérez de León de Petare, Caracas. Se obtuvo que las primeras causas de ingreso, en orden decreciente, a la Unidad de Cuidados Intensivos fueron las siguientes: Infarto Agudo del Miocardio, Heridas por arma de Fuego, Traumatismo Craneoencefálico, Laparotomías Exploratorias, Craneotomías, Politraumatismos, Sepsis abdominales, Accidente Cerebrovascular de tipo Hemorrágico, Cetoacidosis Diabética y las Quemaduras. El sexo masculino predominó sobre el sexo femenino en una relación aproximada de 2,5:1. La distribución de acuerdo a la edad fue muy homogénea en todos los grupos etáreos, predominando ligeramente el grupo entre los 20 y 30 años de edad con un 21,4 por ciento y el de menos de 20 años de edad con un 18,33 por ciento. La tasa de mortalidad promedio de las 10 principales patologías ingresadas en la UCI entre 1992 y 1997 fue 35,56 por ciento, mientras que la tasa de mortalidad promedio asociada a todas las patologías fue 41,80 por ciento

Prevalência de infartos renais em necropsias de chagásicos crônicos / Prevalence of renal infarction in necropsies of chronic chagasic patients

Renal infarction (RI) is usually secondary to arterial obstruction due to emboli originating from the heart. Chronic chagasic patients may present cardiac alterations originating from intracavitary thrombi, even without congestive heart failure (CHF). In this study RI incidence was comparatively evaluated in chronic chagasic individuals, in different anatomoclinic forms and in non chagasic individuals. There has been a review on necropsy reports of individuals aged 20 or over. In 259 necropsies, 78 (30.1 per cent) were chagasics, and 19 of them (24.4 per cent) developed RI, while 27 (15.0 per cent) of the non chagasic individuals presented RI. The ages of chagasics with RI were similar to those of non chagasic individuals. A significant prevalence of RI and thrombosis among chronic chagasic individuals has been found. A significantly higher prevalence of RI among chronic chagasics having CHF (52.6 per cent) was observed when they were compared to other forms of chronic Chagas disease and when compared to non chagasic individuals. It was concluded that RI was more frequent in chronic chagasic individuals, specially those who developed CHF, which probably played a role in the renal manifestations and systemic hemodynamic changes in those patients.

Manifestaçöes cardiovasculares do tabagismo passivo / Cardiovascular effects of passive smoking

A doença aterosclerótica coronariana (DAC) é a principal causa de mortalidade nos países desenvolvidos e em desenvolvimento. Os fatores envolvidos na sua gênese säo multifatoriais e de interaçäo complexa. O tabagismo tem sido imputado como um dos principais fatores de risco de DAC. Contudo, o risco atribuído à exposiçäo da fumaça ambiental do cigarro (FAT), na condiçäo de tabagista passivo (TP), ainda está envolvido em grande controvérsia. Após a implementaçäo de novos métodos epidemiológicos sofisticados e a introduçäo de exames bioquímicos sensíveis permitiram uma melhor compreençäo do impacto ambiental da FAT na saúde do indivíduo TP. Evidências epidemiológicas apontam para um risco de cerca de 20 'por cento' de que o TP possa desenvolver DAC.

La falciformación de los hematies como causa de infarto esplénico en la altura

Presentamos los casos de 8 pacientes varones catalogados como portadores de hemoglobina S,2 del Ex-Hospital Base de Juliaca y 6 pacientes del Hospital Regional "Manuel Núñez Butrón" de Puno, que presentaron infarto esplénico por falciformación de hematíes al ascender a regiones de gran altura, contando 4 de ellos con demostración electroforética de Hb As y los 4 restantes con positividad del test de falciformación realizada con Bisulfito de Sodio al 2 por ciento. 6 pacientes tenían ancestro negroide (2 mestizos, 2 mulatos y 2 negros), un mestizo de ascendencia blanca y finalmente el último de raza blanca. Clínicamente se observa dolor en abdomen superior izquierdo con predominancia en hipocondrio izquierdo, aunque en 2 casos este dolor estaba localizado al principio en abdomen inferior izquierdo; la esplenomegalia, fiebre y leucocitosis con desviación izquierda son hallazgos frecuentes; compromiso pleural izquierdo, ileo paralítico,irritación peritoneal franca o signos de anemia nos indican complicación del infarto de bazo. Tres pacientes fueron intervenidos quirúrgicamente y se les realizó esplenectomía, en dos casos porque presentaban signos compatibles con hemorragia interna, y en el otro caso por infarto masivo de bazo. El bazo infartado en los tres casos estuvo aumentado de tamaño, en más de 5 veces su peso en un caso, y hasta 2 veces su tamaño, lográndose observar necrosis masiva de bazo con compromiso de hasta el 85 por ciento del parénquima. Todos los pacientes, incluídos los intervenidos quirúrgicamente, evolucionaron satisfactoriamente sin presentar complicaciones; las medidas como reposo absoluto, oxigenación contínua y evacuación a regiones de menor altitud, fueron las realizadas.

Lymphnode infarction and lymphoma.

Lymphnode infarction is seen in two sets of situations viz. spontaneous banal infarction of non-neoplastic nodes, and in association with lymphoma. It needs to be differentiated from other causes of lymphnode as a phenomenon occurring synchronous with and occasionally preceding diagnosis of lymphoma is significant.