Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lung is particularly exposed to various inhaled toxic products whose toxicity can be at least partly mediated by the generation of free radicals. Oxidants burden can also result from lung metabolism of xenobiotics or from activation of phagocytes. Free radicals are mainly derived from an univalent sequential reduction of molecular oxygen. Mitochondria is the main location of intracellular production which may also result from auto-oxidation of small molecules or function of some enzymes. To prevent the deleterious effects of free radicals produced by normal metabolism, cells are equipped with an antioxidant system composed of enzymes (superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic substances such as glutathione, iron chelators, vitamin E and C, ceruleoplsamin). Targets of free radicals toxicity are phospholipids by initiation of lipid peroxidation, proteins which may be activated or inactivated via oxidation of sulfhydryl residues. Another target is DNA with possible strand breaks or mutation. Transcription activities can be also altered and it has been recently reported that some transcription factors such as NF-kB can be activated by oxidants. Under these circumstances free radicals may be considered as second messengers. Lung oxygen toxicity has been largely studied. Oxygen-induced lung lesions are non specific. It is possible to induce a resistance to 100% O2 by the pre-exposure of animals to 85% O2. This tolerance phenomenon is associated with an increased lung content in antioxidant substances. The mechanisms of gene regulation of antioxidant enzymes are still poorly understood in eukaryotes. Overproduction of free radicals in the lung is also involved in various clinical settings such as ischemia-reperfusion, exposure to ozone or NO2, acute respiratory distress syndrome, drug induced lung toxicity, pathogenesis of COPD, asthma, cancer and ageing. The precise role of free radicals among other mechanisms of lung injury is still unclear. A better knowledge of free radicals mechanisms of toxicity and of antioxidant regulation is needed to develop antioxidant therapeutic strategies.
 ...
PMID:[Free radicals and respiratory pathology]. 773 56

In an effort to identify preoperative and perioperative factors impacting outcome in repair of juxtarenal abdominal aortic aneurysm (JRAAA), hospital records and CT scans (for calcification, intraluminal thrombus, and aortic diameter) of all patients undergoing JRAAA repair over the past 10 years were reviewed. The 87 men and 25 women had a mean age of 72, and a mean maximal aortic diameter of 6.2 cm. Renal artery stenosis (RAS) and iliac disease were present in 13 (11%) and 40 patients (35%), respectively. Comorbidities included coronary artery disease (n = 49, 44%), COPD (n = 28, 25%), diabetes mellitus (n = 10, 9%), and preoperative renal insufficiency (PRI; Cr >1.4 mg/dL; n = 14, 12%). A midline incision was used in most of the patients (n = 98, 88%). The proximal aortic clamp was placed in the supraceliac (SC) position in 92 (82%) patients, and directly above one or both renal arteries in 20 (18%) patients. The overall mortality was 6% (n = 7). Cardiac complications occurred in 26 patients (23%); pulmonary, in 22 (20%); renal, in 14 (12%); and gastrointestinal, in 10 (9%). No patient experienced mesenteric ischemia. Mean elevation in creatinine was greater in patients with PRI (1.8 mg/dL vs. 0.13 mg/dL, p = 0.04). Mean blood loss (EBL) was 2701 +/- 189 cc, and mean LOS was 16.1 +/- 1.7 days. Age >70 was associated with increased length of stay (LOS) (12.1 days vs. 18.6 days, p = 0.05) and higher mortality (0 vs. 10%, p = 0.02); otherwise there were no significant relationships between pre- and perioperative parameters and any of the measured outcomes including death, postoperative RI, and LOS. Preferential SC clamping may substantially reduce complications of JRAAA repair (such as mesenteric and renal ischemia) related to proximal cuff disease, but cannot overcome the deleterious affects of advanced age and PRI.
 ...
PMID:Optimal operative strategies in repair of juxtarenal abdominal aortic aneurysms. 1252

Based on data reported to the United Network for Organ Sharing through December 2001: 1. The number of heart transplant procedures performed in the United States increased slightly (< 1%) during each of the last 2 complete years from 2,187 transplants during 1999 to 2,197 transplants during 2000, followed by an additional increase in 2001 to 2,202 transplants. A more substantial increase was seen in the number of lung transplants performed: from 890 transplants in 1999 to 956 in 2000 (+7%) and an additional increase to 1,053 transplants in 2001 (+10%). Fewer than 30 heart-lung transplants were performed in 2001. Living-donor lung transplants comprised 2-3% of lung transplants performed between 1995-2001. 2. Pediatric recipients were more frequently on life support in the ICU; more likely to have an ischemia time of at least 4 hours; more often gender mismatched; and more often ABO-compatible rather than ABO-identical with the donor than adult recipients for all thoracic organ types. 3. The most common indication for transplant since 1996 in adult heart recipients was coronary artery disease (50%), followed closely by cardiomyopathy (42%). Among pediatric heart recipients, the 2 most common indications: cardiomyopathy (46%) and congenital heart disease (43%) accounted for approximately 90% of the transplants. The indications for lung transplants were more disparate. In adult lung recipients, the 4 most common diagnoses (COPD - 42%, IPF - 17%, CF - 15% and A1A - 9%) encompassed more than 80% of the transplants. More than half of the pediatric lung transplants were performed in recipients with CF. The 3 most frequently cited indications for adult heart-lung transplant recipients (Eisenmenger's Syndrome, other congenital heart diagnoses and PPH) accounted for greater than 75% of the transplants. 4. Approximately 30-35% of adult heart transplants since 1999 have been performed in patients who were Status 1A. For pediatric transplant recipients, Status 1A comprised 60-70% of the transplants. 5. The one-year survival rate for transplants performed during the first three-quarters of 2001 was 85% for both adult and pediatric heart transplant recipients and 77% for both adult and pediatric recipients of lung transplants. For adult heart-lung transplants performed during 2000, the one-year survival rate was 69%. 6. The long-term patient survival rates were: 39% for adult heart recipients and 50% for pediatric heart recipients at 12 years; 18% at 11 years for adult lung recipients and 31% at 9 years for pediatric lung recipients; and 24% at 11 years for adult heart-lung recipients and 21% at 8 years for pediatric heart-lung recipients. 7. Drug-treated rejection and drug-treated infection were reported to occur before discharge in approximately 20-40% of transplant recipients, with the exception of pediatric lung and heart-lung recipients, with rates varying by organ and age group. Drug-treated infections were reported before discharge in more than 60% of pediatric lung recipients and approximately half of pediatric heart-lung recipients. 8. Approximately 60% of adult heart recipients and 70% of pediatric heart recipients were hospitalized at least once during the first 3 years following their transplant.
 ...
PMID:Thoracic organ transplantation in the US. 1297 35

The definition of proper patient selection criteria remains a prominent item in constant need of attention. While the concept of gathering evidence in order to determine practice continues to be hopelessly ambiguous, it can never be emphasized too much that these univariate results are just a first foray into analysing predictors of survival; all following results should be regarded and interpreted in this perspective. HEART TRANSPLANT SURVIVAL: The 3-year survival rate for heart transplant recipients under age 16 was 83% versus 72% for adult recipients. Acutely retransplanted adult heart recipients had a 3-year survival rate of 36% compared with 72% for recipients of a first heart allograft. Patients suffering from DCM had the best survival rates at 3 years (74%) compared with patients suffering from CAD (70%) or from another end-stage heart disease (67%). With advancing age of the adult recipient, the mortality risk increased. Patients aged 16-40 had a 3-year survival rate of 77%, compared with 74%, 70% and 61% for transplant recipients aged 41-55, 56-65 and over age 65, respectively. The 3-year survival rates for adult recipients transplanted with an heart allograft from a donor aged under 16 or between 16-44 were 78% and 74%, compared with 66% and 63% for donors aged 45-55 and over 55, respectively. The 3-year survival rates for recipients of hearts with cold ischemic times under 2 hours, 2-3, 3-4, 4-5, 5-6 and more than 6 hours were 74%, 75%, 70%, 65%, 54% and 40%, respectively. Transplanting a female donor heart into a male recipient was associated with the worst prognosis: the 3-year survival rates were 73%, 71%, 66% and 76%, respectively, for the donor/recipient groups male/male, male/female, female/male and female/female, respectively. When the donor-to-recipient body weight ratio was below 0.8, the 3-year survival rate was 64%, compared to 72% for weight-matched pairs and 74% for patients who received a heart from an oversized donor (p=0.004). Better survival rates were obtained for better HLA-matched transplants. The 3-year survival rates were 75%, 89%, 78%, 78%, 69%, 72%, and 71% for HLA-A,-B,-DR zero, 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.04). Survival was significantly associated with the CMV serologic status of the donor and recipient; the 3-year survival rates were: D+/R+, 71%; D+/R-, 69%; D- R-, 76%; and D-/R+, 76% (p=0.04). Patients in an ICU had a 3-year survival rate of 62%, compared to 72% for patients in a general ward and 74% for outpatients (p<0.0001). Patients that were on a VAD and there-upon transplanted had a 3-year survival rate of 65%, compared to 73% for patients without a VAD (p=0.004). Being on a ventilator was a major risk factor for death after transplantation; patients on ventilator support at the time of the transplant had a 3-year survival rate of 52% compared to 73% for the other patients (p<0.0001). LUNG TRANSPLANT SURVIVAL: The 3-year survival rate for children (73%) appeared to be better than the adult rate (61%; p=0.8). Adult lung transplant survival was significantly worse in the case of a repeat lung transplant; a 3-year retransplant survival rate of 42% was obtained compared with 61% for first transplants (p=0.049). With respect to the underlying end-stage lung disease, no statistically significant difference in long-term survival could be detected in this cohort. The 3-year survival rates were: 62% for COPD/Emphysema, 70% for CF, 58% for IPF, 64% for Alpha-1 ATD and 56% for PPH (p=0.2). Our data demonstrated no effect of the recipient's age on long-term lung transplant survival, except for 2 senior patients in this cohort. At 3-years the survival rates for recipients aged 16-40, 41-55 and 56-65 were 65%, 60% and 62%, respectively (p=0.05). The 3-year survival rates for transplants performed with lungs from donors aged under 16, 16-44, 45-55 and over 55 was 57%, 64%, 55% and 62%, respectively (p=0.1) No association between the duration of cold ischemic time and 3-year survival was observed; under 3 hours, 3-4, 4-5, 5-6 and over 6 hours of ischemia resulted in 3-year survival rates of 53%, 59%, 64%, 68% and 57%, respectively (p=0.2). Early posttransplant outcome tended to be better for gender-matched transplants, while transplanting a female donor lung into a male recipient was associated with the worst prognosis. The 3-year survival rates were 65% for male/male, 63% for male/female, 48% for female/male and 61% for female/female (p=0.009). No effect of donor-to-recipient weight match was observed in this Eurotransplant cohort; when the donor-to-recipient weight ratio was below 0.8, the 3-year survival rate was 57%, compared with 59% for weight-matched pairs and 64% for patients who received a lung from an oversized donor (p=0.5). Long-term survival after lung transplantation was influenced by HLA matching. The 3-year survival rates were 100%, 68%, 70%, 65%, 54% and 55% for the HLA-A,-B,-DR 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.06). A donor CMV+ and recipient CMV- match was a risk factor for long-term mortality, with 3-year survival rates of 56% for D+/R+, 55% for D+/R-, 71% for D-/R- and 62% for D-/R+ transplants (p=0.046). En-bloc transplantation of both lungs yielded worse early results, but the 3-year survival rates for patients who underwent single (60%), bilateral sequential double lung (63%) and en-bloc double lung transplantation (56%) were not different (p=0.2). Ventilator dependency was associated with a significantly reduced survival at 3 years. Patients on a ventilator support at the time of the transplant had a 3-year survival rate of 48% compared with 63% for other patients (p=0.006).
 ...
PMID:Three-year survival rates for all consecutive heart-only and lung-only transplants performed in Eurotransplant, 1997-1999. 1538

Acid-base balance is altered in a variety of common pathologies, including COPD, ischemia, renal failure, and cancer. Because of robust cellular pH homeostatic mechanisms, most of the pathological alterations in pH are expressed as changes in the extracellular, systemic pH. There are data to indicate that altered pH is not simply an epiphenomenon of metabolic or physiologic imbalance but that chronic pH alterations can have important sequelae. MRSI and MRI measurements indicate that pH gradients of up to 1.0 pH unit can exit within 1-cm distance. Although measurement of blood pH can indicate systemic problems, it cannot pinpoint the lesion or quantitatively assess the magnitude of excursion from normal pHe. Hence, there is a need to develop pHe measurement methods with high spatiotemporal resolution. The two major approaches being investigated include magnetization transfer methods and relaxation methods. pH-dependent MT effects can observed with endogenous signals or exogenously applied CEST agents. While endogenous signals have the advantage of being fully noninvasive and relatively straightforward to apply, they lack a full biophysical characterization and dynamic range that might be afforded by future CEST agents. pH-dependent relaxivity also requires the injection or infusion of exogenous contrast reagents. In both MT and relaxographic approaches, the magnitude of the effect, and, thus, the ability to quantify pHe, depends on a spatially and temporally varying concentration of the CR. A number of approaches have been proposed to solve this problem and, once it is solved, pH imaging methods will be applicable to human clinical pathologies.
 ...
PMID:pH imaging. A review of pH measurement methods and applications in cancers. 1556

Pulmonary oxidant stress plays an important pathogenetic role in disease conditions including acute lung injury/adult respiratory distress syndrome (ALI/ARDS), hyperoxia, ischemia-reperfusion, sepsis, radiation injury, lung transplantation, COPD, and inflammation. Reactive oxygen species (ROS), released from activated macrophages and leukocytes or formed in the pulmonary epithelial and endothelial cells, damage the lungs and initiate cascades of pro-inflammatory reactions propagating pulmonary and systemic stress. Diverse molecules including small organic compounds (e.g. gluthatione, tocopherol (vitamin E), flavonoids) serve as natural antioxidants that reduce oxidized cellular components, decompose ROS and detoxify toxic oxidation products. Antioxidant enzymes can either facilitate these antioxidant reactions (e.g. peroxidases using glutathione as a reducing agent) or directly decompose ROS (e.g. superoxide dismutases [SOD] and catalase). Many antioxidant agents are being tested for treatment of pulmonary oxidant stress. The administration of small antioxidants via the oral, intratracheal and vascular routes for the treatment of short- and long-term oxidant stress showed rather modest protective effects in animal and human studies. Intratracheal and intravascular administration of antioxidant enzymes are being currently tested for the treatment of acute oxidant stress. For example, intratracheal administration of recombinant human SOD is protective in premature infants exposed to hyperoxia. However, animal and human studies show that more effective delivery of drugs to cells experiencing oxidant stress is needed to improve protection. Diverse delivery systems for antioxidants including liposomes, chemical modifications (e.g. attachment of masking pegylated [PEG]-groups) and coupling to affinity carriers (e.g. antibodies against cellular adhesion molecules) are being employed and currently tested, mostly in animal and, to a limited extent, in humans, for the treatment of oxidant stress. Further studies are needed, however, in order to develop and establish effective applications of pulmonary antioxidant interventions useful in clinical practice. Although beyond the scope of this review, antioxidant gene therapies may eventually provide a strategy for the management of subacute and chronic pulmonary oxidant stress.
 ...
PMID:Antioxidant strategies in respiratory medicine. 1640 15

Inflammatory eicosanoids generated by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism are now known to have at least 6 receptors: OXE, which recognizes 5-HETE and 5-oxo-ETE; a putative receptor recognizing a potent 5-oxo-ETE metabolite, FOG(7); the LTB(4) receptors, BLT1 and BLT2; the cysteinyl leukotriene receptors, CysLT(1) and CysLT(2), which recognize leukotrienes LTC(4), LTD(4), LTE(4) and LTF(4). The 5-LO pathway is activated in many diseases and invokes inflammatory responses not affected by glucocorticoids, but therapy with selective BLT1 or CysLT(1) antagonists in asthma has met with variable success. Studies show that 5-LO pathway eicosanoids are not primary mediators in all cases of asthma, but may be especially important in severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, COPD, idiopathic pulmonary fibrosis, atherosclerosis, atopic dermatitis, acne and ischemia-related organ injury. These disorders appear to involve multiple 5-LO pathway eicosanoids and receptor subtypes, suggesting that inhibition of the pathway at the level of 5-LO may be necessary for maximal efficacy.
 ...
PMID:Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. 1748 54

Lung transplantation is one of the most difficult fields of contemporary transplantology. The operation was performed on a 53-year-old female who had been suffering from terminal stage COPD. The period of cold ischemia for the right and left lung was 1 hour 30 minutes and 2 hours 25 minutes respectively. The total operation time was 4 hours and 40 minutes. There were no surgical complications. There were no signs of transplant rejection 6 weeks after the operation. The considerable decrease in dispnea and increase in quality of life were registered during the follow-up. FEV1 was increased by 80% and 6 minute walk test distance was increased by 200 meters.
 ...
PMID:[The first successful bilateral lung transplantation in Russia]. 1767 17

We compared exercise capacity (peak O2 uptake; VO(2peak)) and lower limb vasodilatory capacity in 9 patients with moderate COPD (FEV1 52.7 +/- 7.6% predicted) and 9 age-matched healthy control subjects. VO(2peak) was measured via open circuit spirometry during incremental cycling. Calf blood flow (CBF) measurements were obtained at rest and after 5 minutes of ischemia using venous occlusion plethysmography. While VO(2peak) was significantly lower in the COPD patients (15.8 +/- 3.5 mL x kg(-1) x min(-1)) compared with the control group (25.2 +/- 3.5 mL x kg(-1) x min(-1)), there were no significant differences between groups in peak CBF or peak calf conductance measured 7 seconds post-ischemia. VO(2peak) was significantly correlated with peak CBF and peak conductance in the control group, whereas no significant relationship was found between these variables in the COPD group. However, the rate of decay in blood flow following ischemia was significantly slower (p < 0.05) for the COPD group (-0.036 +/- 0.005 mL x 100 mL(-1) x min(-1) x S(-1)) when compared with controls (-0.048 +/- 0.015 mL x 100 mL(-1) x min(-1) x S(-1)). The results suggest that the lower peak exercise capacity in patients with moderate COPD is not related to a loss in leg vasodilatory capacity.
 ...
PMID:Lower limb vasodilatory capacity is not reduced in patients with moderate COPD. 1804 5

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA and COPD, which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1beta secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1beta targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.
 ...
PMID:Interleukin-1beta targeted therapy in severe persistent asthma (SPA) and chronic obstructive pulmonary disease (COPD): proposed similarities between biphasic pathobiology of SPA/COPD and ischemia-reperfusion injury. 1916 Sep 37


1 2 3 Next >>