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981.
Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats 总被引:8,自引:0,他引:8 下载免费PDF全文
Walter PB Knutson MD Paler-Martinez A Lee S Xu Y Viteri FE Ames BN 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(4):2264-2269
Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (< or =5 microg/day) and iron-normal (800 microg/day) rats and in both groups after daily high-iron supplementation (8,000 microg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 microg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 x nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake. 相似文献
982.
Masood Akhtar Anthony N. Damato Jeremy N. Ruskin William P. Batsford C.Pratap Reddy Andres R. Ticzon Malkiat S. Dhatt Joseph A.C. Gomes Antonino H. Calon 《American heart journal》1978,95(1):22-42
In 20 patients with PSVT without ventricular pre-excitation, the site of reentry and functional characteristics of Ant. and Ret. pathways were studied. Three distinct patterns of PSVT were observed. In 13 patients (group I) in whom A-V node was the site of reentry, the interval between the Ant. H bundle deflection and the following atrial echo response (H-Ae) measured 30 to 85 msec. and the Ae was partially or completely obscured by ventricular electrogram. The ratio between the H-Ae and the subsequent Ae-H interval ranged 1:3.1–17.3. In a majority of Group I patients (eight out of 13) the Ret. conduction was better than Ant. conduction, as the VACS sustained a 1:1 response at faster paced rates than AVCS. The FRP of the AVCS in Group I was determined by the A-V node in all patients and significantly exceeded the FRP of the VACS; the latter was determined by the HPS in 12 out of 13 patients. In four patients (Group II) a V-A AP silent antegradely was operative during PSVT. The H-Ae in Group II valued 145 to 200 msec. and the Ae clearly followed the ventricular electrogram, the H-Ae: Ae-H being 1:0.5–1.7. The V-A conduction in all Group II patients was better than the A-V conduction. A-V node determined the FRP of the AVCS, whereas AP determined the FRP of the VACS in Group II patients, and the former significantly exceeded the latter. Good correlation existed between PSVT, Ant. and Ret. conduction patterns in Group I and Group II patients.In three patients (Group III) the H-Ae measured 270 to 470 msec. with an H-Ae:Ae-H of 1:0.2–0.4, a relationship quite the opposite of Group I patients. No definite relationship existed between PSVT, Ant. and Ret. conduction patterns in Group III patients. The data in Group III patients were compatible with (1) A-V nodal reentry with reversal of conduction balance compared to Group I, (2) intra-atrial reentry, and (3) enhanced atrail automaticity.It is concluded (1) the site of reentry in patients with PSVT is variable, (2) a fair estimation of reentry site can be made from H-Ae and Ae-H relationship, (3) all patients with PSVT have intact V-A conduction and in most the V-A conduction is better than A-V conduction, and (4) in the majority of patients with PSVT refractoriness of the AVCS exceeds that of the VACS. 相似文献
983.
We describe 2 elderly patients with splenomegaly and progressive bone marrow failure due to infiltration by leukemic prolymphocytes with a single prominent nucleolus. In each case the leukemia cells had a unique helper T cell phenotype with complement receptors and contained coarse blocks of acid alpha-naphthyl butyrate. A 14q+ chromosome was among the abnormalities that marked one abnormal T cell clone. Histology of the spleen showed mainly red pulp infiltration merging with periarteriolar regions and different from the pseudonodular pattern described in many cases of B cell prolymphocytic leukemia (PLL). Ultrastructurally, leukemia cells contained dense lysosomes, perinuclear clusters of 10-nm microfilaments but no distinctive cytoplasmic inclusions previously described in (B cell) PLL. We suggest that early phenotyping of leukemia cells may enable consideration of monoclonal antibody therapy in elderly patients with bone marrow failure resistant to chemotherapy. 相似文献
984.
Jana Hurnakova Hana Hulejova Jakub Zavada Martin Komarc Lucie Andres Cerezo Herman Mann Jiri Vencovsky Karel Pavelka Ladislav Senolt 《Clinical rheumatology》2018,37(8):2055-2062
Approximately half of patients with rheumatoid arthritis (RA) have normal C-reactive protein (CRP) levels. Calprotectin is a promising and likely more specific biomarker of disease activity than conventionally used acute phase reactants. We aimed to analyse the levels of serum calprotectin in RA patients with clinically active disease and with normal/low CRP. A total of 160 RA patients underwent clinical examination (DAS28-ESR and CDAI). The levels of calprotectin were analysed in patients with moderate to high disease activity with normal/low CRP levels and in 32 healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160 (46.3%) were in remission or had low disease activity according to DAS28 and had normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite having moderate to high disease activity. In these patients, calprotectin levels were significantly higher than those in patients who had normal/low CRP and were in remission or showed low disease activity (2.7?±?1.5 vs. 2.1?±?1.2 μg/mL, p?=?0.043), which differed from those in healthy subjects (2.7?±?1.5 vs. 1.9?±?1.2 μg/mL, p?=?0.011). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive disease despite normal/low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p?=?0.043). The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so. 相似文献
985.
Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes 总被引:10,自引:0,他引:10
Maneiro E Martín MA de Andres MC López-Armada MJ Fernández-Sueiro JL del Hoyo P Galdo F Arenas J Blanco FJ 《Arthritis and rheumatism》2003,48(3):700-708
OBJECTIVE: Osteoarthritis (OA) is a degenerative rheumatic disease that is associated with extracellular matrix degradation and chondrocyte apoptosis in the articular cartilage. The role of mitochondria in degenerative diseases is widely recognized. We undertook this study to evaluate mitochondrial function in normal and OA chondrocytes and to examine age-related changes in mitochondria. METHODS: Mitochondrial function was evaluated by analyzing respiratory chain enzyme complexes and citrate synthase (CS) activities as well as changes in mitochondrial membrane potential (Delta Psi m). The activities of mitochondrial respiratory chain complexes (complex I: rotenone-sensitive NADH-coenzyme Q(1) reductase; complex II: succinate dehydrogenase; complex III: antimycin-sensitive ubiquinol cytochrome c reductase; and complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from OA and normal cartilage. Delta Psi m was measured by JC-1 using flow cytometry. Statistical analysis was performed using the Mann-Whitney U test and Student's t-test as well as several models of multiple linear regression. RESULTS: OA articular chondrocytes had reduced activities of complexes II and III compared with cells from normal cartilage. However, the mitochondrial mass was increased in OA. Cultures of OA chondrocytes contained a higher proportion of cells with de-energized mitochondria. We found no relationship between mitochondrial function and donor age either in normal or in OA chondrocytes. CONCLUSION: These findings suggest the involvement of mitochondrial function in the pathophysiology of OA. Cartilage degradation by OA and cartilage aging may be two different processes. 相似文献
986.
Fateh Bazerbachi Eric J. Vargas Monika Rizk Daniel B. Maselli Taofic Mounajjed Sudhakar K. Venkatesh Kymberly D. Watt John D. Port Rita Basu Andres Acosta Ibrahim Hanouneh Naveen Gara Meera Shah Manpreet Mundi Matthew Clark Karen Grothe Andrew C. Storm Michael J. Levy Barham K. Abu Dayyeh 《Clinical gastroenterology and hepatology》2021,19(1):146-154.e4
987.
Lauren E. Schrock Jonathan W. Mink Douglas W. Woods Mauro Porta Dominico Servello Veerle Visser‐Vandewalle Peter A. Silburn Thomas Foltynie Harrison C. Walker Joohi Shahed‐Jimenez Rodolfo Savica Bryan T. Klassen Andre G. Machado Kelly D. Foote Jian‐Guo Zhang Wei Hu Linda Ackermans Yasin Temel Zoltan Mari Barbara K. Changizi Andres Lozano M. Auyeung Takanobu Kaido Yves Agid Marie L. Welter Suketu M. Khandhar Alon Y. Mogilner Michael H. Pourfar Benjamin L. Walter Jorge L. Juncos Robert E. Gross Jens Kuhn James F. Leckman Joseph A Neimat Michael S. Okun 《Movement disorders》2015,30(4):448-471
Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25‐year‐old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post‐DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients. © 2014 International Parkinson and Movement Disorder Society 相似文献
988.
989.
Mauricio Gonzalez-Garcia Andres Caballero Claudia Jaramillo Dario Maldonado Carlos A. Torres-Duque 《The Journal of asthma》2015,52(8):823-830
Objective: There are differences in the prevalence and risk factors of asthma around the world. The epidemiological situation of adults 40 years and older is not well established. Our aim was to determine the prevalence, underdiagnosis and risk factors of asthma and wheezing in adults in Colombia. Methods: A cross-sectional, population-based study including 5539 subjects from 40 to 93 years selected by a probabilistic sampling technique in five cities was conducted. Measurements: respiratory symptoms and risk factors questionnaire and spirometry. Definitions: (a) Wheezing: Affirmative answer to the question “have you ever had two or more attacks of “wheezes” causing you to feel short of breath?” (b) Asthma: Wheezing definition and FEV1/FVC post-bronchodilator?≥?70%. (c) Underdiagnosis: Asthma definition without a physician-diagnosis. Logistic regression was used for exploring risk factors. Results: Prevalence of asthma was 9.0% (95% CI: 8.3-9.8) and wheezing 11.9% (95% CI: 11.0-12.8). Asthma underdiagnosis was 69.9% and increased to 79.0% in subjects 64 years or older. The risk factors related to asthma and/or wheezing were: living in Bogota or Medellin, female gender, first degree relative with asthma, respiratory disease before 16 years of age, obesity, no education, indoor wood smoke exposure and occupational exposure to dust particles, gases or fumes. Conclusion: We described the epidemiologic situation of asthma in adults 40 years and older in Colombia. In addition to some recognized risk factors, our data supports the association of indoor wood smoke and occupational exposures with asthma and wheezing. Underdiagnosis of asthma in adults was high, particularly in older subjects. 相似文献
990.
Samira M Sadowski Axel Andres Philippe Morel Eduardo Schiffer Jean-Louis Frossard Alexandra Platon Pierre-Alexandre Poletti Leo Bühler 《World journal of gastroenterology : WJG》2015,21(43):12448-12456
AIM: To study the safety of epidural anesthesia(EA),its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis(AP).METHODS: From 2005 to August 2010,patients with predicted severe AP [Ranson score ≥ 2,C-reactive protein 100 or necrosis on computed tomography(CT)] were prospectively randomized to either a group receiving EA or a control group treated by patientcontrolled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale(VAS). Parameters for clinical severity such as length of hospital stay,use of antibiotics,admission to the intensive care unit,radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head,body and tail of the pancreas.RESULTS: We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group(mean score 4.15 ± 2.54 vs 3.38 ± 1.75,respectively,P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively(P = NS). The median duration of EA was 5.7 d,and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30(43%) of measurements in the EA group vs 2/27(7%) in the control group(P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group(P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group(0.2 vs 2.33,P = 0.034 at 10 d). Length of stay and mortality were not statistically different between the 2 groups(26 d vs 30 d,P = 0.65,and 0% for both respectively).CONCLUSION: Our study demonstrates that EA increases arterial perfusion of the pancreas and improves the clinical outcome of patients with AP. 相似文献