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1.
Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep
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Flavio Torres Alejandro González‐Candia Camilo Montt Germán Ebensperger Magdalena Chubretovic María Serón‐Ferré Roberto V. Reyes Aníbal J. Llanos Emilio A. Herrera 《Journal of pineal research》2015,58(3):362-373
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. 相似文献
2.
Tsuneharu Miki Yoichi Mizutani Hideyuki Akaza Seiichiro Ozono Taiji Tsukamoto Toshiro Terachi Katsusuke Naito Norio Nonomura Isao Hara Osamu Yoshida The Japan Blood Cell Transplantation Study Group for Testicular Germ Cell Tumor 《International journal of urology》2007,14(1):54-59
OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT. 相似文献
3.
Añez G 《Investigación clínica》2005,46(1):1-3
In November 2004, sponsored by the World Bank, the Venezuelan Foundation of Science, Technology and Innovation (Fonacit) and the Venezuelan Institute of Scientific Research (IVIC), delegates from the different virology research groups of the country, met in Caracas-Venezuela, with the aim to establish the "Venezuelan Virology Network". The symposium entitled "Molecular biology applied to virus of health importance in Venezuela", was divided into three areas, including human and animals viruses related to public health: 1) Dengue, others arboviruses and Hemorrhagic Fevers; 2) diarrhea-related and others veterinary viruses and 3) Hepatitis, HIV and others sexually transmitted viruses. This symposium allowed the delegates to evaluate the current strengths, weaknesses and needs of the different laboratories, becoming evident the necessity of developing collaborative work between the groups that share the same interests or lines of research; and also their need to exchange technical resources, human and bibliographical material and consequently, avoiding the duplication of efforts and the unnecessary cost of resources. One of the main strengths of Venezuelan virology is the presence, in most laboratories, of researchers with studies of fourth level and multidisciplinary teams of work. We aspire to achieve the raised objectives in the event, to the benefit of our virology and even more important, of our people. 相似文献
4.
Diestra JE Scheffer GL Català I Maliepaard M Schellens JH Scheper RJ Germà-Lluch JR Izquierdo MA 《The Journal of pathology》2002,196(2):213-219
The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH. 相似文献
5.
Daniel H Berrocal Germán E González Alejandro Fernández Susana Perez Luciana Wilensky Celina Morales Liliana Grinfeld Ricardo J Gelpi 《Cardiovascular pathology》2008,17(5):289-296
BACKGROUND: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. OBJECTIVES: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. METHODS: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. RESULTS: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28+/-0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10+/-0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. CONCLUSIONS: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion. 相似文献
6.
Escalante-Mañe Ana M. Hernández-Nuñez Emanuel Méndez-Novelo Roger I. Giácoman-Vallejos Germán González-Sánchez Avel A. Quintanilla-Mena Mercedes A. Romellón-Orozco Mariana E. Puch-Hau Carlos 《Bulletin of environmental contamination and toxicology》2022,108(3):526-531
Bulletin of Environmental Contamination and Toxicology - We report the chemical characterisation and toxic effects of municipal solid waste landfill leachates on the embryonic development of Danio... 相似文献
7.
8.
M. Majem M. Galán F. J. Pérez M. Muñoz S. Chicote G. Soler M. Navarro M. Martínez-Villacampa X. García del Muro E. Dotor B. Laquente J. R. Germà 《Clinical & translational oncology》2007,9(12):784-788
Objective To provide an outpatient facility to improve the management of chemotherapy toxicity in cancer patients.
Patients and methods We set up an oncology acute toxicity unit (OATU) to improve toxicity management. A telephone helpline was the initial contact
which filters out inappropriate non-toxicity-related events. Patients were provided an information booklet describing the
possible side effects of the chemotherapy and the helpline telephone number. A specialist nurse received the calls and consulted
the doctor if necessary. Depending on requirements, the patient’s problem was resolved by telephone, or a consultation visit
at the OATU was arranged.
Results Between February 1999 and August 2001, 1126 patients made 2007 contacts with the OATU. The most common tumours were breast
(26%), colorectal (20%) and lung (20%). The telephone helpline was used in 87% of contacts and 37% were considered inappropriate.
Of the 1263 appropriate contacts, the most frequent chemotherapy schedules that had been administered were 5FU-leucovorin
(11.2%) and CMF (10.4%). The most frequent side effects were fever (35.5%), diarrhoea (18.5%), mucositis (16.2%) and emesis
(13%). The problem was resolved by telephone in 48% of cases and 52% required attendance in the OATU, of which 40% required
hospital admission, i.e., 21.1% of the initial appropriate helpline contacts. The most frequent reason was Grade 3–4 neutropenic
fever (56.5%).
Conclusions The OATU enables prompt and efficient access of patients to medical oncology facilities in the event of toxicity due to chemotherapy.
Unnecessary emergency room use is avoided while oncology outpatient and hospitalisation facilities are optimised. 相似文献
9.