Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.
 ...
PMID:Sodium 4-phenylbutyrate protects against cerebral ischemic injury. 1522 15

Lung transplantation is currently the most effective means of improving survival and quality of life in patients with end-stage cystic fibrosis. In reviewing our 6-year experience we sought to evaluate complications and survival after sequential bilateral lung transplantation. Between October 1996 and October 2002, 114 patients with cystic fibrosis were referred to us from 15 Italian regional centers and 2 support centers for cystic fibrosis as possible candidates for lung transplantation. Of these 114 patients, 99 were included in the waiting list and 15 were refused. The mean time spent on the waiting list was 6.8+/-5.2 months (range 1 day-21 months) for those patients receiving lung transplantation, and 5.4+/-4.5 months (range 10 days-18 months) for those 35 patients who died while on the waiting list. A total 55 patients (6 children and 49 adults), mean age 25.6+/-6.6 years (range 9-52 years), 29 males, underwent bilateral sequential lung transplantation. One patient had a second transplantation 14 months after the first. The most frequent medical non-infective complications after transplantation were chronic renal failure (n=27 patients), diabetes (n=31), osteoporosis (n=17), arterial hypertension (n=14), seizures (n=4), transient cerebral ischaemia (n=1), and transient bilateral blindness (n=1). Bacterial lower airways respiratory infections with the organisms that colonized patients' airways before lung transplantation developed in 42 patients; cytomegalovirus (CMV) infection in 41; and opportunistic infections of the lung with Pneumocystis carinii in 3 patients. Cultures of sputum or bronchoalveolar lavage fluid grew Aspergillus fumigatus in nine patients; aspergillosis of right bronchial anastomosis developed in one patient and a lung infection in another. Another patient had a pulmonary infection secondary to Aspergillus niger. An average of 1.3 episodes of acute rejection developed per patient in the first 6 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome was 95% at 1 year, 82.5% at 2 years, 70% at 3 years, and 65% at 4, 5 and 6 years. Actuarial survival rates were 80% at 1 month, 79% at 1 year, 74% at 2 years, 70% at 3 years and 58% at 4, 5 and 6 years. Ten patients (17.8%) died in the early postoperative period (1-30 days) for the following reasons: primary graft failure (n=4), multiorgan failure (n=3), Burkholderia cepacia sepsis (n=1), myocardial infarction (n=1), and pulmonary embolism (n=1). Mortality was accounted for by 9 patients (16%) who died from 9 to 43 months after lung transplantation, for the following reasons: P. carinii infection (n=2), bronchiolitis obliterans syndrome (n=4), A. fumigatus pulmonary infection (n=1), unknown cause (n=1) and suicide (n=1). In conclusion, the leading causes of morbidity after lung transplantation for cystic fibrosis are pulmonary bacterial infection and opportunistic infections. Bronchiolitis obliterans develops in more than half of lung transplant recipients who survive for more than 3 years and is an important cause of death in the late post transplantation period.
 ...
PMID:Lung transplantation for cystic fibrosis: 6-year follow-up. 1591 93