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Organ Damage (organ + damage)
Kinds of Organ Damage Selected AbstractsLaboratory Models Available to Study Alcohol-Induced Organ Damage and Immune Variations: Choosing the Appropriate ModelALCOHOLISM, Issue 9 2010Nympha B. D'Souza El-Guindy The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium "Methods of Ethanol Application in Alcohol Model,How Long is Long Enough" at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. [source] An updated view of hemostasis: mechanisms of hemostatic dysfuntion associated with sepsisJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2005DACVECC, Kate Hopper BVSc Abstract Objective: To review the current understanding of mechanisms involved in normal hemostasis and to describe the changes associated with pro-inflammatory disease processes such as sepsis. Data sources: Original research articles and scientific reviews. Human data synthesis: Organ damage caused by sepsis is created in part by the interdependent relationship between hemostasis and inflammation. Markers of coagulation have been found to have prognostic value in human patients with sepsis and there are both experimental and clinical investigations of the therapeutic potential of modulating the hemostatic system in sepsis. Improvement of 28-day all-cause mortality in severe sepsis by treatment with recombinant human activated Protein C strongly supports the interdependence of hemostasis and inflammation in the pathophysiology of sepsis. Veterinary data synthesis: Publications reporting clinical evaluation of the hemostatic changes occurring in septic dogs or cats are minimal. Experimental animal models of sepsis reveal significant similarity between human and animal sepsis and may provide relevance to clinical veterinary medicine until prospective clinical evaluations are published. Conclusions: It is now apparent that inflammation and the coagulation system are intimately connected. Understanding this relationship provides some insight into the pathogenesis of the hemostatic changes associated with sepsis. This new updated view of hemostasis may lead to the development of novel therapeutic approaches to sepsis and disseminated intravascular coagulation in veterinary medicine. [source] Linear and nonlinear measures of blood pressure variability: Increased chaos of blood pressure time series in patients with panic disorderDEPRESSION AND ANXIETY, Issue 2 2004Vikram K. Yeragani M.B.B.S. Abstract Arterial blood pressure (BP) variability increases progressively with the development of hypertension and an increase in BP variability is associated with end organ damage and cardiovascular morbidity. On the other hand, a decrease in heart rate (HR) variability is associated with significant cardiovascular mortality. There is a strong association between cardiovascular mortality and anxiety. Several previous studies have shown decreased HR variability in patients with anxiety. In this study, we investigated beat-to-beat variability of systolic and diastolic BP (SBP and DBP) in normal controls and patients with panic disorder during normal breathing and controlled breathing at 12, and 20 breaths per minute using linear as well as nonlinear techniques. Finger BP signal was obtained noninvasively using Finapres. Standing SBPvi and DBP BPvi (log value of BP variance corrected for mean BP divided by HR variance corrected for mean HR) were significantly higher in patients compared to controls. Largest Lyapunov exponent (LLE) of SBP and DBP, a measure of chaos, was significantly higher in patients in supine as well as standing postures. The ratios of LLE (SBP/HR) and LLE (DBP/HR) were also significantly higher (P < .001) in patients compared to controls. These findings further suggest dissociation between HR and BP variability and a possible relative increase in sympathetic function in anxiety. This increase in BP variability may partly explain the increase in cardiovascular mortality in this group of patients. Depression and Anxiety 19:85-95, 2004. © 2004 Wiley-Liss, Inc. [source] Echocardiographic Left Ventricular Mass in African-AmericansECHOCARDIOGRAPHY, Issue 2 2003The Jackson Cohort of the Atherosclerosis Risk in Communities Study Characterization of target organ damage from hypertension is of particular interest in African-Americans, and evidence from electrocardiographic studies suggests that left ventricular hypertrophy is a frequent clinical finding of considerable prognostic importance. Echocardiographic studies may permit more precise characterization of the pathologic impact of hypertension on cardiac structure and function. The objective of this study is to characterize left ventricular (LV) structure including measures of wall thickness, septal thickness, internal dimension, and mass in a middle-aged sample of African-Americans using echocardiography. This study is a cohort (cross-sectional) study in which 2445 middle-aged African-American study participants from a population-based sample initially enrolled by the Atherosclerosis Risk in Communities, Jackson, Mississippi Examination Center in 1987,1989 underwent an M-mode echocardiograpic examination at their third or fourth clinic visit in 1993,1996. Measures of LV mass, even where indexed by size were conspicuously greater in men compared to women, and men exhibited a demonstrably steeper gradient of LV mass across the rather restricted age range of the study. However, when gender specific thresholds for LV hypertrophy were utilized, African-American men appear to have lower prevalence of LV hypertrophy than women. The lowest prevalence of LV hypertrophy was observed in African-American men who did not have hypertension (28.4%). The findings confirm previous suggestions from electrocardiographic investigations that cardiac hypertrophy is common, if not epidemic in middle-aged African-American men and women, whether or not they have hypertension. (ECHOCARDIOGRAPHY, Volume 20, February 2003) [source] Iron homeostasis: new players, newer insightsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008Eunice S. Edison Abstract Although iron is a relatively abundant element in the universe, it is estimated that more than 2 billion people worldwide suffer from iron deficiency anemia. Iron deficiency results in impaired production of iron-containing proteins, the most prominent of which is hemoglobin. Cellular iron deficiency inhibits cell growth and subsequently leads to cell death. Hemochromatosis, an inherited disorder results in disproportionate absorption of iron and the extra iron builds up in tissues resulting in organ damage. As both iron deficiency and iron overload have adverse effects, cellular and systemic iron homeostasis is critically important. Recent advances in the field of iron metabolism have led to newer understanding of the pathways involved in iron homeostasis and the diseases which arise from alteration in the regulators. Although insight into this complex regulation of the proteins involved in iron homeostasis has been obtained mainly through animal studies, it is most likely that this knowledge can be directly extrapolated to humans. [source] Systemic IFN-, drives kidney nephritis in B6.Sle123 miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Anna-Marie Fairhurst Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source] Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: a potential relationship to sudden infant death syndromeFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2004Jane Blood-Siegfried Abstract Data increasingly implicate a possible role of immune and inflammatory responses to infection in sudden infant death syndrome (SIDS). We have previously described a dual challenge model that results in pathology, organ damage, vascular collapse and unexplained death similar to that seen in SIDS. In this study, we examined changes in inflammatory cytokine mRNA in the lung and liver and regulation of pathways associated with nitric oxide production. Our data suggest that priming of the immune system by mild viral infection disturbs normal inflammatory response to endotoxin. This results in an increased nitric oxide synthase production, most likely the cause of liver pathology and clotting abnormalities. [source] Evaluating the physiological and physical consequences of capture on post-release survivorship in large pelagic fishesFISHERIES MANAGEMENT & ECOLOGY, Issue 2 2007G. B. SKOMAL Abstract, Sharks, tunas and billfishes are fished extensively throughout the world. Domestic and international management measures (quotas, minimum sizes, bag limits) mandate release of a large, yet poorly quantified, number of these fishes annually. Post-release survivorship is difficult to evaluate, because standard methods are not applicable to large oceanic fishes. This paper presents information on the current approaches to characterising capture stress and survivorship in sharks, tunas and marlins. To assess mortality associated with capture stress, researchers must examine the cumulative impacts of physical trauma and physiological stress. Physical trauma, manifested as external and internal tissue and organ damage, is caused by fishing gear and handling. Gross examination and histopathological sampling have been used to assess physical trauma and to infer post-release survivorship. Exhaustive anaerobic muscular activity and time out of water cause physiological stress, which has been quantified in these fishes through the analyses of blood chemistry. Conventional, acoustic and archival tagging have been used to assess post-release survivorship in these species. Future studies relating capture stress and post-release survivorship could yield information that helps fishermen increase survivorship when practicing catch and release. [source] Importance of arterial stiffness as cardiovascular risk factor for future development of new type of drugsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2008Pierre Boutouyrie Abstract Cardiovascular risk prediction relies on classical risk factors such as age, gender, lipids, hypertension, smoking and diabetes. Although the value of such scales of risk is high for populations, its value for individual is reduced and too much influenced by non-modifiable risk factors (age and gender). Biomarkers of risk have been deceiving and genome wide scan approach is too recent. Target organ damage may help in selecting patients at high risk and in determining intervention. Aortic pulse wave velocity, an index of aortic stiffness, has been widely validated as providing additional risk predictions beyond and above classical risk factors, and has now entered into official guidelines. Many interventions (dietary, behaviour, drug treatment) were shown to influence arterial stiffness positively, but little evidence of a direct effect of intervention on arterial stiffness independent of blood pressure is available. New pharmacological targets and new drugs need to be identified. To become a surrogate endpoint for drug development, there is a need to demonstrate that regression arterial stiffness is associated with improved outcome. In parallel to this demonstration, points to be improved are the homogenization and spreading of the technique of measurement, the establishment of a reference value database. [source] Clinical pharmacology and therapeutic use of antioxidant vitaminsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Ramón Rodrigo Abstract The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta-analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta-analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage. [source] Rationale, design and methods of the OSCAR study: observational study on cognitive function and systolic blood pressure reduction in hypertensive patientsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Atul Pathak Abstract Data from several recent clinical trials have suggested a beneficial effect of antihypertensive medications on preservation of cognitive function. Eprosartan, an angiotensin type-1 receptor antagonist (ARA) with dual action on both pre- and postsynaptic angiotensin type 1 receptors, may be effective in the control of SBP and the prevention of cognitive decline. The OSCAR (Observational Study on Cognitive function And SBP Reduction) study is an international longitudinal observational study with a duration of 6 months intended to examine the impact of the ARA eprosartan on cognitive function (assessed using the Mini-Mental State Examination [MMSE]) and control of systolic blood pressure (SBP) in a large international population of hypertensive patients managed in a standard primary care setting. A total of 100 000 hypertensive patients, aged ,50 years and with SBP of >140 mmHg will be recruited by more than 20 000 primary care physicians in 27 countries. These patients will receive eprosartan 600 mg once a day for 6 months. The MMSE, a globally validated cognitive screening test, will be performed at baseline, and after 6 months of treatment. After the first month of monotherapy, eprosartan treatment may, at the absolute discretion of individual investigators, be supplemented with other antihypertensive medications for the remainder of the study. The primary outcome indices are the mean relative change in MMSE score and the absolute change from baseline in SBP in the study population as a whole and in subsets of patients according to various factors among them: ethnicity, comorbidities (i.e. target organ damage, diabetes), baseline cognitive level and baseline blood pressure level. The secondary objectives are to identify factors influencing SBP and MMSE changes. The OSCAR trial is the first international observational study focusing on MMSE in a wide international cohort of hypertensive patients. The results are expected in 2007. [source] Ischemic preconditioning of the murine liver protects through the Akt kinase pathway,HEPATOLOGY, Issue 3 2006Kunihiko Izuishi Hepatic ischemia-reperfusion (I/R) injury occurs in the settings of transplantation, trauma, and elective liver resection. Ischemic preconditioning has been used as a strategy to reduce inflammation and organ damage from I/R of the liver. However, the mechanisms involved in this process are poorly understood. We examined the role of the phosphatidylinositol 3 (PI3) kinase/Akt-signaling pathway during hepatic ischemic preconditioning (IPC). Prior to a prolonged warm ischemic insult, BALB/c mice were subjected to a 20-minute IPC period consisting of 10 minutes of ischemia and 10 minutes of reperfusion. Mice undergoing IPC demonstrated a significantly greater level and earlier activation of Akt in the liver compared with control animals. IPC also resulted in markedly less hepatocellular injury and improved survival compared with control animals. Akt activation associated with hepatic IPC suppressed the activity of several modulators of apoptosis, including Bad, glycogen synthase kinase ,, and caspase-3. In addition, IPC also inhibited the activities of c-Jun N -terminal kinase and nuclear factor ,B after I/R. Pretreatment of mice with PI3 kinase inhibitors completely abolished Akt phosphorylation and the protective effects seen with IPC. In conclusion, these results indicate that the PI3 kinase/Akt pathway plays an essential role in the protective effects of IPC in hepatic I/R injury. Modulation of this pathway may be a potential strategy in clinical settings of ischemic liver injury to decrease organ damage. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2006;44:573,580.) [source] Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease lociIMMUNOLOGICAL REVIEWS, Issue 1 2001Marie M. Griffiths Summary: Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA,QTLs can modulate arthritis independently. These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA,QTLs. Also, CIA,QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA. [source] Management of hypertension and stroke prevention: results of the Italian cardiologist surveyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009G. Tocci Summary Objective: To provide an overview of current habits, priorities, perceptions and knowledge of cardiologists with regard to hypertension and stroke prevention in outpatient practice. Methods: A sample of 203 cardiologists operating in outpatient clinics and randomly selected amongst members of the largest Italian Outpatient Cardiologist Association were interviewed by e-mail, in April,May 2007. Results: The interviewed cardiologists reported that hypertensive outpatients represent a large percentage of their practice population, in which the clinical priority was blood pressure (BP) reduction. Stroke was identified as the most important event to prevent and it was also perceived as the most preventable hypertension-related cardiovascular event. A remarkably high rate of achieved BP control was reported, to a degree that it is inconsistent with current epidemiological reports and with the relatively low percentage use of combination therapies declared by cardiologists. Additional risk factors, organ damage, diabetes mellitus and atrial fibrillation were consistently reported in hypertensive patients. Among antihypertensive drug classes, a preference for angiotensin-converting enzyme inhibitors has been expressed by the majority of physicians; this choice was generally justified by evidence derived from international trials or by the antihypertensive efficacy of this drug class. Conclusions: The results confirm the presence of weaknesses in the current services for patients with hypertension, even when being managed by cardiologists. Discrepancies between perceptions and reality, or clinical practice and guideline recommendations are also highlighted. An analysis of these aspects may help to identify current areas of potential improvement for stroke prevention in the clinical management of hypertension in cardiology practice. [source] Berend Houwen Memorial Lecture: ISLH Las Vegas May 2009INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2009The pathogenesis, management of thrombotic microangiopathies Summary Thrombotic microangiopathies are a relatively rare group of congenital and inherited disorders caused by defects in processing the ultra large forms of von Willibrand factor which pathologically give rise to platelet rich microthrombi in the micro arterial circulation leading to end organ damage particularly in the brain, heart and kidneys. Identification of the ADAMTS 13 gene has led to the definition of congenital deficiency of its activity or failure of activity due to the development of an inhibitory IgG antibody. The idiopathic autoimmune form of the disease is the most common. There are various subgroups of acquired TTP associated with HIV infection, pregnancy, pancreatitis, associated with bone marrow transplantation, various disseminated malignancies and certain drugs, particularly Clopidogrel. Diagnostic assays are now becoming widely available to identify ADAMTS 13 activity and also acquired antibodies to the enzyme. Mainline treatment is associated with daily plasma exchange with associated other immunosuppressant treatments particularly steroids and recently the use of Rituximab, a monoclonal anti-CD20 antibody. Despite improvement in treatment modalities there is still significant mortality of 10,20%, particularly if there is a delay in initiating plasma exchange. Relapse also occurs in 20,50% of patients although this may be improved by Rituximab therapy. [source] Managing Emergency Hypertension in Aortic Dissection and Aortic Aneurysm SurgeryJOURNAL OF CARDIAC SURGERY, Issue 2006Ali Khoynezhad M.D. Similar development has occurred in regard to the treatment of thoracic aortic aneurysms. Treatment options are medical, surgical, or endovascular. Aortic dissection always presents as a hypertensive emergency and requires parenteral antihypertensive agents to control blood pressure (BP) and prevent target organ damage. Diligent control of BP is of utmost importance in order to stop the progression of dissection with possible aortic branch malperfusion. Treatment for hypertensive emergency begins in the intensive care unit and continues during and after surgery. Improved surgical techniques as well as newer, safer agents that reduce BP to acceptable levels have reduced the risk of mortality and improved prognosis in the postoperative period. Nevertheless, mortality rates remain high, and successful management of aortic dissection and aortic aneurysm still poses a clinical challenge. [source] Risk-Based Classification of Hypertension and the Role of Combination TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 2008Matthew R. Weir MD The recognition of a continuous relationship between elevated blood pressure (BP) and cardiovascular risk has influenced national and international guidelines for the classification, prevention, and management of hypertension. The most recent report (2003) of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure uses BP thresholds to define categories of normal, prehypertension, and hypertension. A new definition proposed by the Hypertension Writing Group in 2005 offers an approach to diagnosis and management based on global or total risk. Thus, even in the absence of sustained elevations in BP, patients may have a moderate to high risk of vascular events due to the presence of additional cardiovascular risk factors, disease markers, and target organ damage. The 2007 European guidelines continue to classify hypertension based on cutoffs while also placing emphasis on multivariate formulations for cardiovascular risk assessment and goals of therapy. All 3 sets of guidelines acknowledge the necessity of using ,2 antihypertensive agents to attain BP goals in many patients. [source] Laboratory Models Available to Study Alcohol-Induced Organ Damage and Immune Variations: Choosing the Appropriate ModelALCOHOLISM, Issue 9 2010Nympha B. D'Souza El-Guindy The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium "Methods of Ethanol Application in Alcohol Model,How Long is Long Enough" at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. [source] Melatonin ameliorates chronic renal failure-induced oxidative organ damage in ratsJOURNAL OF PINEAL RESEARCH, Issue 4 2004Göksel, ener Abstract:, Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05,0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05,0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit. [source] Mean Corpuscular Volume and ADH1C Genotype in White Patients With Alcohol-Associated DiseasesALCOHOLISM, Issue 5 2005Leimin Sun Background: Alcohol abuse is associated with several gastrointestinal diseases, such as esophageal carcinoma, chronic alcoholic pancreatitis, and liver cirrhosis. Increased mean corpuscular volume (MCV) has been recognized as a biomarker for alcohol abuse and heavy drinkers. Recent studies from Japan revealed that macrocytosis is related to ALDH-2/2 genotype, leading to increased acetaldehyde accumulation. It has also demonstrated that increased MCV values could also be an independent biomarker for esophageal cancer in Asians. Therefore, the aim of the current study was to investigate possible associations of MCV value with polymorphisms of ADH1C in white patients with alcohol-associated esophageal carcinoma, chronic alcoholic pancreatitis, and alcoholic cirrhosis as well as in heavy drinkers without organ damage. Methods: In this study, a total of 510 alcoholic patients were enrolled with esophageal cancer (n= 98), chronic pancreatitis (n= 98), alcoholic liver cirrhosis (n= 151), and alcohol abuse without gastrointestinal disease (n= 163). ADH1C genotyping was performed by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis from whole blood. The relation between MCV and ADH1C gene polymorphisms (ADH1C*1 and 1C*2) controlled for the amount of drinking, smoking, and age were investigated using both univariate and multivariate analysis. Results: In univariate analysis, higher alcohol consumption was associated with increased MCV. Other variables were not associated with macrocytosis. In multiple linear regression analysis, after adjustment for age and smoking, higher alcohol consumption and female sex were independently associated with higher MCV values. No other variables, including which alcohol-associated disease the patient had, had an independent effect. Adding ADH genotype rendered no independent significant effect on MCV value. Conclusions: In a white population, MCV values were not associated with genotype polymorphisms of ADH1C. In contrast to findings in Asians, macrocytosis does not seem to be an independent biomarker for esophageal cancer. The role of ADH1C polymorphism in increasing MCV and the potential use of MCV as a marker for esophageal carcinoma are still pending. [source] Pain rate and social circumstances rather than cumulative organ damage determine the quality of life in adults with sickle cell disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Charlotte F.J. van Tuijn First page of article [source] Hereditary iron overload: Update on pathophysiology, diagnosis, and treatmentAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2006Massimo Franchini Abstract Hereditary hemochromatosis, a very common genetic defect in the Caucasian population, is characterized by progressive tissue iron overload which leads to irreversible organ damage if it is not treated timely. The elucidation of the molecular pathways of iron transport through cells and its control has led to the understanding of various genetic iron-loading conditions. Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed. Am. J. Hematol. 81:202,209, 2006. © 2006 Wiley-Liss, Inc. [source] High-density lipoprotein prevents organ damage in endotoxemia,RESEARCH IN NURSING & HEALTH, Issue 3 2007Ru-Ping Lee Abstract High-density lipoprotein (HDL) may decrease organ injury in sepsis. This study was designed using an animal model to mimic people who had a high HDL level and to test HDL effects on preventing organ damage in endotoxemia. Endotoxemia was induced by an infusion of lipopolysac-charide (LPS) after HDL or LDL administration. Levels of blood biochemical substances, nitrate/nitrite, and TNF-, in sera were measured. Pathological examinations were performed 72 hours after LPS infusion. HDL decreased the endotoxin-induced elevation of AST, ALT, BUN, creatinine, LDH, CPK, nitrate/nitrite, and TNF-,. On histological examination, neutrophil infiltration was lower in the HDL group. HDL had a significant effect in preventing endotoxin-induced organ damage. © 2007 Wiley Periodicals, Inc. Res Nurs Health 30: 250,260, 2007 [source] Coat condition of ringtailed lemurs, Lemur catta, at Berenty Reserve, Madagascar: II.AMERICAN JOURNAL OF PRIMATOLOGY, Issue 3 2009tail alopecia associated with Leucaena leucocepahala Abstract Fur condition in wild ringtailed lemurs, Lemur catta, was recorded during September,November birth seasons 2001,2006 at Berenty Reserve, Madagascar. Body coat condition was scored on a scale from BS 0: full, smooth coat with guard hairs, to BS5: half or more of back and limbs hairless. Tail condition was scored from TS 0: full, to TS 5: half or more hairless. Where troop core areas included stands of Leucaena leucocephala, alopecia was dramatically more frequent than in similar areas without leucaena, including many animals with score BS5 or TS5, "bald lemur syndrome." Female coats were worse than males,' possibly related to female dominance and access to this preferred food. Tails in non-leucaena-feeding females tend to remain full, even if coats deteriorate, but with leucaena-feeding female tails are highly correlated with coat condition and equally bare. Coat and tail condition in L. catta reflected not only the dietary toxin but individual differences as well as differences between adjacent troops that may result from territorially mediated access to the environment. Leucaena contains the non-protein amino acid mimosine, a known cause of alopecia, wasting, and organ damage in livestock, although the effects are usually reversible. This is the first case of its effect in wildlife. Leucaena is an agroforestry tree introduced throughout the tropics. In high dietary concentrations leucaena might potentially affect any browsing mammal. Am. J. Primatol. 71:199,205, 2009. © 2008 Wiley-Liss, Inc. [source] Outcomes of Heart Transplantation for Cardiac Amyloidosis: Subanalysis of the Spanish Registry for Heart TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009E. Roig Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 ± 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 ± 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated. [source] HLA,DRB4 as a genetic risk factor for Churg-Strauss syndromeARTHRITIS & RHEUMATISM, Issue 9 2007Augusto Vaglio Objective To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease. Methods Low-resolution genotyping of HLA,A, HLA,B, and HLA,DR loci and genotyping of TNFA ,238A/G and TNFA ,308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls. Results The frequency of the HLA,DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; ,2 = 12.64, P = 0.0003, corrected P [Pcorr] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47,3.99). The HLA,DRB4 gene, present in subjects carrying either HLA,DRB1*04, HLA,DRB1*07, or HLA,DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; ,2 = 16.46, P = 0.000058, Pcorr = 0.000232, OR 2.49, 95% CI 1.58,3.09). Conversely, the frequency of the HLA,DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; ,2 = 7.62, P = 0.0057, Pcorr = 0.0228, OR 0.54, 95% CI 0.35,0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA),positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA,DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001). Conclusion These findings indicate that HLA,DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease. [source] Systemic lupus erythematosus in a multiethnic US cohort: Clinical features, course, and outcome in patients with late-onset diseaseARTHRITIS & RHEUMATISM, Issue 5 2006Ana M. Bertoli Objective To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE). Methods A nested case,control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age ,49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self-reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late-onset lupus, damage accrual, and mortality as dependent variables were then performed. Results Two hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late-onset lupus was an independent predictor of damage accrual (t -test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98,141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07,37.56) (P < 0.001). Conclusion Patients with late-onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early-onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients. [source] Intrinsic Toxicity of Hemoglobin: How to Counteract ItARTIFICIAL ORGANS, Issue 2 2009Jan Simoni Abstract The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness. In some subjects, vasoconstriction and decreased blood flow to the vital organs, heart attack, stroke, systemic inflammation, organ damage, and even death, have been attributed to the transfusion of these experimental products. Hb is a well-known pressor agent and strong oxidant, although the full understanding of its intrinsic toxicity is yet to be uncovered. In particular, the complete mechanism of Hb-induced vasoconstriction needs full elucidation. Knowledge of the biological events that trigger the induction of genes upon treatment with redox-active Hb, as well as its catabolism, is still incomplete. It seems that our limited knowledge of free Hb effects in vivo is the main reason for not yet having a viable substitute of human blood. The future for universal red cell substitutes is in the new-generation products that address all of Hb's intrinsic toxicity issues. [source] Clinical remission of idiopathic hypereosinophilic syndrome in a RottweilerAUSTRALIAN VETERINARY JOURNAL, Issue 8 2009FE James Idiopathic hypereosinophilic syndrome (HES) is a rare syndrome for which Rottweilers appear to over-represent the canine cases. A 6-month-old female entire Rottweiler presented with seizures following a traumatic incident. The dog was identified as having a marked, sustained eosinophilia and investigations did not identify an underlying cause. Concurrently, the dog had chronic eosinophilic hepatitis with impaired liver function and mesenteric eosinophilic lymphadenitis. The dog went on to have spontaneous resolution of HES and normal liver function was subsequently documented. To date, the dog is still alive, more than 4 years after initial presentation. The diagnosis of idiopathic HES in Rottweilers may not carry a poor prognosis and the condition may spontaneously resolve, even in cases with documented organ damage. [source] Sickle cell leg ulcers: a frequently disabling complication and a marker of severityBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008M. Halabi-Tawil Summary Background, Leg ulcers are a poorly known and underestimated complication of sickle cell disease (SCD), but in our experience they often appear as a severely disabling condition, associated with the most severe forms of the disease. Objectives, To assess the characteristics, complications, repercussion on quality of life and associations of SCD ulcers. Methods, Case series of 20 patients followed in a French referral centre for SCD and who had previous/present leg ulcers. Results, Median ulcerated area was 12 cm˛ and median time spent with ulcers was 29·5 months. Locoregional infections developed in 85%, ankle stiffness in 50% and mood disorders in 85%. Ninety per cent of patients needed analgesics, 20% being opioids. Median loss of time from work was 12·5 months. The Short Form 36 Health Survey showed physical and mental component summary scores of 41·5 and 40·7, respectively, indicating severe alteration close to that found in lung cancer or haemodialysis. Two categories of SCD leg ulcers were distinguished, defined by a 1-year duration cut off. The ,prolonged' ulcers had larger surfaces, tended to recur more frequently and led to more infection and depression. Several SCD complications were associated with leg ulcers, notably priapism, pulmonary hypertension, stroke and acute chest syndrome. Conclusions, Leg ulcers are a major complication of SCD, given their severe consequences and frequent association with other specific organ damage, and they constitute in their ,prolonged' form a severely disabling condition that remains an important therapeutic challenge. [source] | ||||||||||||||||||||||||||||||||||