Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling / 生理学报

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.

Classification of Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides, that are characterized by inflammation in the small vessels, ranging from capillaries to arterioles or venules. AAV is divided into three variants based on the clinical manifestations and histological findings such as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). MPA often induces rapid progressive necrotising glomerulonephritis, and occasionally induces diffuse alveolar hemorrhage. In contrast, GPA preferentially affects the respiratory tracts from the bronchus to the nasal cavity. GPA can also involve the kidneys, but the frequency of renal involvement is less than MPA. EGPA is based on allergic components such as asthma, peripheral eosinophilia, migratory eosinophilic pneumonia and eosinophil infiltration. Since 1982, when the association between ANCA and systemic vasculitis was first reported, several classification criteria for AAV have been proposed. This review describes the classification criteria for and nomenclature of AAV from the 1990 American College of Rheumatology (ACR) classification criteria to the 2012 revised Chapel Hill consensus conference (CHCC) nomenclature of Vasculitides. New classification trials for AAV such as AAV based on the ANCA-types (myeloperoxidase-ANCA vasculitis, proteinase 3-ANCA vasculitis and ANCA negative vasculitis) and the ACR/European League Against Rheumatism (EULAR) 2017 provisional classification criteria for GPA were also introduced. In addition, the histopathological classification of ANCA-associated glomerulonephritis and the revised 2017 international consensus on testing of ANCAs in GPA and MPA are also discussed.

Involvement of immune responses in pulmonary arterial hypertension; lessons from rodent models / 한국실험동물학회지

Pulmonary hypertension (PH) is a pathological state with sustained elevation of pulmonary artery (PA) pressure. Since the pathogenesis of PH is mostly irreversible, the disease often comes up with poor prognosis. Pulmonary arterioles are affected by deteriorative changes, such as development of occlusive lesions of thickening of arterial walls. Such processes increase the pulmonary arterial pressure thus lead to consequent injuries such as right ventricle failure. Proliferation, or resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) and fibroblasts, are characteristic changes observed in the PA in pulmonary arterial hypertension (PAH) patients. PAH can either occur idiopathically or come with other diseases. Emerging evidences suggest that pro-inflammatory processes are closely related to the development of PAH. Therefore, it is inferred that immune cells could be the key factors in PAH development. In this review, we summarize the way how each types of immune cells participate in PAH. We would also like to list the current rodent models used for PAH study.

Cerebrovascular reactivity to hypercapnia during sevoflurane or desflurane anesthesia in rats / 대한마취과학회지

BACKGROUND: Hypercapnia causes dilation of cerebral vessels and increases cerebral blood flow, resulting in increased intracranial pressure. Sevoflurane is reported to preserve cerebrovascular carbon dioxide reactivity. However, the contribution of inhaled anesthetics to vasodilatory responses to hypercapnia has not been clarified. Moreover, the cerebrovascular response to desflurane under hypercapnia has not been reported. We examined the effects of sevoflurane and desflurane on vasodilatory responses to hypercapnia in rats. METHODS: A closed cranial window preparation was used to measure the changes in pial vessel diameters. To evaluate the cerebrovascular response to hypercapnia and/or inhaled anesthetics, the pial vessel diameters were measured in the following states: without inhaled anesthetics at normocapnia (control values) and hypercapnia, with inhaled end-tidal minimal alveolar concentration (MAC) of 0.5 or 1.0 of either sevoflurane or desflurane at normocapnia, and an MAC of 1.0 of sevoflurane or desflurane at hypercapnia. RESULTS: Under normocapnia, 1.0 MAC, but not 0.5 MAC, of sevoflurane or desflurane dilated the pial arterioles and venules. In addition, under both 1.0 MAC of sevoflurane and 1.0 MAC of desflurane, hypercapnia significantly dilated the pial arterioles and venules in comparison to their diameters without inhaled anesthetics. The degrees of vasodilation were similar for desflurane and sevoflurane under both normocapnia and hypercapnia. CONCLUSIONS: Desflurane induces cerebrovascular responses similar to those of sevoflurane. Desflurane can be used as safely as sevoflurane in neurosurgical anesthesia.

Effect of Ambrisentan Therapy on the Expression of Endothelin Receptor, Endothelial Nitric Oxide Synthase and NADPH Oxidase 4 in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model

BACKGROUND AND OBJECTIVES: Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model. METHODS: Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis. RESULTS: Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4. CONCLUSIONS: Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.

Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study

ABSTRACT BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

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.

CD57 (Leu-7, HNK-1) immunoreactivity seen in thin arteries in the human fetal lung / 대한해부학회지

CD57 (synonyms: Leu-7, HNK-1) is a well-known marker of nerve elements including the conductive system of the heart, as well as natural killer cells. In lung specimens from 12 human fetuses at 10–34 weeks of gestation, we have found incidentally that segmental, subsegmental, and more peripheral arteries strongly expressed CD57. Capillaries near developing alveoli were often or sometimes positive. The CD57-positive tissue elements within intrapulmonary arteries seemed to be the endothelium, internal elastic lamina, and smooth muscle layer, which corresponded to tissue positive for a DAKO antibody reactive with smooth muscle actin we used. However, the lobar artery and pulmonary arterial trunk as well as bronchial arteries were negative. Likewise, arteries in and along any abdominal viscera, as well as the heart, thymus, and thyroid, did not express CD57. Thus, the lung-specific CD57 reactivity was not connected with either of an endodermal- or a branchial arch-origin. CD57 antigen is a sugar chain characterized by a sulfated glucuronic acid residue that is likely to exist in some glycosphingolipids. Therefore, a chemical affinity or an interaction might exist between CD57-positive arterioles and glycosphingolipids originating from alveoli, resulting in acceleration of capillary budding to make contact with the alveolar wall. CD57 might therefore be a functional marker of the developing air-blood interface that characterizes the fetal lung at the canalicular stage.

Ventilation-induced changes correlate to pulmonary vascular response and VEGF, VEGFR-1/2, and eNOS expression in the rat model of postnatal hypoxia

Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P<0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P<0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia.

Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension

BACKGROUND AND OBJECTIVES: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). METHODS: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. RESULTS: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. CONCLUSIONS: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.

Pars Plana Vitrectomy for Cystoid Macular Edema in a Retinitis Pigmentosa Patient

PURPOSE: To report the first case of cystoid macular edema in a retinitis pigmentosa patient with pars plana vitrectomy. CASE SUMMARY: A 43-year-old female visited our hospital with visual disturbances of both eyes. Corrected visual acuity was 20/22 in the right eye and 20/25 in the left eye. Peripheral depigmentation and atrophy of the retinal pigment epithelium, pigmentary retinal degeneration, and attenuated arterioles were observed in both eyes. Cystoid macular edema was observed on optical coherence tomography which showed that the central macular thickness was 308 µm in the right eye and 422 µm in left eye. Intravitreal aflibercept was injected into the left eye. One month after injection, the central macular thickness showed no response with a thickness of 449 µm. An intravitreal dexamethasone implant was then injected, 1 month after injection, the central macular thickness was 367 µm. Six months after injection, the patient again complained of visual disturbance of the left eye with a corrected visual acuity of 20/70. Vitreous opacity was observed and the central macular thickness was 501 µm. The patient underwent pars plana vitrectomy. Three days after surgery, the central macular thickness was 320 µm. One year after surgery, the corrected visual acuity was 20/33 and the central macular thickness was 311 µm. CONCLUSIONS: Pars plana vitrectomy due to cystoid macular edema in a retinitis pigmentosa patient has not been previously reported in the Republic of Korea. Pars plana vitrectomy can therefore be an effective treatment for cystoid macular edema in retinitis pigmentosa patients.

Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT₂R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT₂R.

Change of voltage-gated potassium channel 1.7 expressions in monocrotaline-induced pulmonary arterial hypertension rat model / 소아과

PURPOSE: Abnormal potassium channels expression affects vessel function, including vascular tone and proliferation rate. Diverse potassium channels, including voltage-gated potassium (Kv) channels, are involved in pathological changes of pulmonary arterial hypertension (PAH). Since the role of the Kv1.7 channel in PAH has not been previously studied, we investigated whether Kv1.7 channel expression changes in the lung tissue of a monocrotaline (MCT)-induced PAH rat model and whether this change is influenced by the endothelin (ET)-1 and reactive oxygen species (ROS) pathways. METHODS: Rats were separated into 2 groups: the control (C) group and the MCT (M) group (60 mg/kg MCT). A hemodynamic study was performed by catheterization into the external jugular vein to estimate the right ventricular pressure (RVP), and pathological changes in the lung tissue were investigated. Changes in protein and mRNA levels were confirmed by western blot and polymerase chain reaction analysis, respectively. RESULTS: MCT caused increased RVP, medial wall thickening of the pulmonary arterioles, and increased expression level of ET-1, ET receptor A, and NADPH oxidase (NOX) 4 proteins. Decreased Kv1.7 channel expression was detected in the lung tissue. Inward-rectifier channel 6.1 expression in the lung tissue also increased. We confirmed that ET-1 increased NOX4 level and decreased glutathione peroxidase-1 level in pulmonary artery smooth muscle cells (PASMCs). ET-1 increased ROS level in PASMCs. CONCLUSION: Decreased Kv1.7 channel expression might be caused by the ET-1 and ROS pathways and contributes to MCT-induced PAH.

Papel da Apoptose em Obstetrícia / Role of Apoptosis in Obstetrics

Apoptose, ou morte celular programada, é um mecanismo fisiológico universal entre mamíferos que regula o equilíbrio entre proliferação e morte celular a fim de manter a homeostase tecidual. Nesse processo, a apoptose poderá ser iniciada intrinsicamente por via mitocondrial ou, extrinsecamente, mediada por sinalização via receptor de morte ou em resposta a elementos exógenos como citocinas e processos não excludentes, complementares e com ativação cruzada. As moléculas envolvidas no controle das vias de ativação da apoptose são as proteínas anti, pró-apoptóticas e caspases. Esse fenômeno biológico, além de desempenhar um papel importante no controle de diversos processos vitais, está associado a inúmeras complicações da gravidez como toxemia, crescimento intrauterino restrito, parto pré-termo, diabetes gestacional, abortamento, gravidez ectópica e a transformação maligna da mola hidatiforme. No denominador comum dessas doenças está o desconhecimento de sua etiopatogenia e o desenvolvimento/funcionamento placentário anormal. Compreender todas essas alterações deverá interessar não apenas ao pesquisador dessas moléstias, mas também aos clínicos que tratam essas doenças no intuito de se incorporar novas tecnologias na rotina médica e na melhoria das perspectivas prognósticas e terapêuticas dentro da obstetrícia.(AU)

Apoptosis, or programmed cell death, is a universal physiological mechanism in mammals, which regulates the balance between cell proliferation and death in order to maintain tissue homeostasis. In this process, apoptosis can be initiated intrinsically or extrinsically by mitochondrial pathway, mediated by death receptor signaling or in response to exogenous factors such as cytokines and processes not mutually exclusive, complementary and cross-activation. The molecules involved in the control of apoptosis activation pathways are anti and pro-apoptotic proteins as well as caspases. This biological phenomenon, besides play an important role in the control of many vital processes, is associated with many complications of pregnancy such as toxemia, intrauterine growth, preterm birth, gestational diabetes, miscarriage, ectopic pregnancy and malignant in transformation hydatiform mole. The common denominator of these diseases is the lack of knowledge about its pathogenesis and development/abnormal placental function. Understand all these changes should interest not only to the researchers, but also for clinicians who treat these diseases in order to incorporate new technologies in the medical routine and in improving prognostic and therapeutic perspectives in obstetrics.(AU)

Lesão de Dieulafoy do fundo gástrico / Dieulafoys lesion of the gastric fundus

Hemorragia digestiva alta (HDA) é uma emergência clínica exteriorizada através de melena, hematêmese, além de alterações hemodinâmicas decorrentes de perda volêmica. Existem vários diagnósticos etiológicos causadores de hemorragias digestivas altas; dentre eles, uma causa rara é lesão de Dieulafoy, sendo relacionada acerca de 2% dos casos de HDA. Neste relato, descreveremos um caso de lesão de Dieulafoy, evidenciando a relevância desta lesão como um importante diagnóstico diferencial nas causas de hemorragia digestiva alta. O procedimento diagnóstico e o manejo atual são fundamentados pela endoscopia digestiva alta. A hemostasia endoscópica é realizada, utilizando técnicas como eletrocoagulação, injeções com adrenalina e hemoclips.

Upper gastrointestinal bleeding (UGBI) is a clinical emergency externalized through melena, hematemesis and hemodynamic changes due to volume loss. There are a lot of etiological diagnosis of gastroduodenal hemorrhages, including Dieulafoy which is a rare cause related about 2% of the UGBI cases. In this report we describe a case of Dieulafoy lesion highlighting the importance of this lesion as a rare and important differential diagnosis in cases of upper gastrointestinal bleeding. The current diagnostic and management is justified by endoscopy. Endoscopic hemostasis is performed using techniques such as electrocoagulation, injections of adrenaline and hemo-clips.

Therapeutic effect of prostaglandin E1 in monocrotaline-induced pulmonary arterial hypertension rats / 대한해부학회지

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration. However, many of the currently available anti-PAH drugs suffer from a number of limitations, including short biological half-life, and poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with selectivity toward pulmonary circulation when it is administered via the pulmonary route. However, PGE1 has a very short half-life of 5–10 minutes. Therefore, we hypothesized that long-term effect of PGE1 could reduce mal-adaptive structural remodeling of the lung and heart and prevent ventricular arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and endothelin receptor A, and the expression of fibrosis. These results support the notion that PGE1 can improve the functional properties of RV, highlighting its potential benefits for heart and lung impairment.

Malignant Hypertension with Pulmonary Alveolar Hemorrhage Needing Dialysis / 이화의대지

A 35-year-old man presented with progressive dyspnea and hemoptysis. His blood pressure was 230/140 mmHg and serum creatinine level was 20.13 mg/dL. Chest radiography and computed tomography revealed pulmonary hemorrhage. His renal function was low, thus emergent renal replacement therapy was required. Malignant hypertension and acute kidney injury were diagnosed, and antihypertensive therapy and hemodialysis started immediately. Renal biopsy was performed to examine the underlying disease. Typical pathological changes of malignant hypertension, fibrinoid necrosis of the afferent arterioles, and proliferative endoarteritis at the interlobular arteries were observed. His renal function improved gradually and pulmonary hemorrhage completely disappeared with administration of antihypertensive agents. Here, we report this rare case of malignant hypertension with pulmonary alveolar hemorrhage and speculate that the hemorrhage may be related to vascular injuries at the alveolar capillary level caused by malignant hypertension.

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.

The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure / 소아과

PURPOSE: Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. METHODS: The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. RESULTS: The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. CONCLUSION: Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function.

Window to Heart; Ocular Manifestations of Hypertension / 한양의대학술지

Systemic hypertension affects not only the heart, kidneys, brain, and large arteries but also the eyes. High blood pressure (BP) causes a series of pathophysiological changes in the retinal vasculature, including focal and diffuse narrowing of the retinal arteriole, opacification of the arteriolar wall, and compression of the venules by arterioles. In severe cases, hemorrhage, nerve fiber layer infraction, and disc swelling can occur. Systemic hypertension results in various retinal vascular diseases, such as hypertensive retinopathy, retinal vein or artery occlusion, retinal arterial macroaneurysm, and nonarteritic ischemic optic neuropathy. High BP also increases the risk of development and progression of diabetic retinopathy. Signs of hypertensive retinopathy are predictive of target-organ damages, including cardiovascular and cerebrovascular diseases. While managing patients with hypertensive retinopathy, physicians should be aware of the management of cardiovascular and cerebrovascular risk factors.