Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro.

Free radicals may be involved in apoptosis although this is the subject of some controversy. Furthermore, the source of free radicals in apoptotic cells is not certain. The aim of this study was to elucidate the role of oxidative stress in the induction of apoptosis in serum-deprived fibroblast cultures and in weaned lactating mammary glands as in vitro and in vivo experimental models, respectively. Oxidative damage to mtDNA is higher in apoptotic cells than in controls. Oxidized glutathione (GSSG) levels in mitochondria from lactating mammary gland are also higher in apoptosis. There is a direct relationship between mtDNA damage and the GSSG/reduced glutathione (GSH) ratio. Furthermore, whole cell GSH is decreased and GSSG is increased in both models of apoptosis. Glutathione oxidation precedes nuclear DNA fragmentation. These signs of oxidative stress are caused, at least in part, by an increase in peroxide production by mitochondria from apoptotic cells. We report a direct relationship between glutathione oxidation and mtDNA damage in apoptosis. Our results support the role of mitochondrial oxidative stress in the induction of apoptosis.     

Acute orthogeriatric care (II). Clinical aspects

The present article reviews the clinical principles of acute orthogeriatric care. The application of geriatric medicine to patients with hip fracture is explained. The principal stages of geriatric intervention in this process are mentioned, as are the interventions to be carried out by the geriatric team. Subsequently, we discuss the management of several frequent problems in these patients, such as high surgical risk, pain management, anaemia, delirium, malnutrition, and discharge planning. Lastly, the characteristics of several kinds of patients with special characteristics are mentioned, such as those diagnosed with dementia, nursing home residents or the oldest-old. Areas of improvement in the acute phase are also reviewed, such as mortality reduction, functional outcome improvement and the need for more efficient resource use in patients in the acute phase of hip fracture.     

Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2 therapy

Viña, José, Emilio Servera, Miguel Asensi, JuanSastre, Federico V. Pallardó, José A. Ferrero, JoséGarcía-de-la-Asunción, Vicente Antón, and JulioMarín. Exercise causes blood glutathione oxidation inchronic obstructive pulmonary disease: prevention by O₂therapy. J. Appl. Physiol. 81(5):2199-2202, 1996.The aim of the present study was to determinewhether glutathione oxidation occurs in chronic obstructive pulmonarydisease (COPD) patients who perform exercise and whether this could beprevented. Blood glutathione red-ox ratio [oxidized-to-reducedglutathione (GSSG/GSH)] was significantly increased when patientsperformed exercise for a short period of time until exhaustion. Theirresting blood GSSG/GSH was 0.039 ± 0.008 (SD)(n = 5), whereas after exercise itincreased to 0.085 ± 0.019, P < 0.01. Glutathione oxidation associated with exercise was partiallyprevented by oxygen therapy (resting value: 0.037 ± 0.014, n = 5; after exercise: 0.047 ± 0.016, n = 5, P < 0.01). We conclude that lightexercise causes an oxidation of glutathione in COPD patients, which canbe partially prevented by oxygen therapy.

     

Acute orthogeriatric care (I). Healthcare issues

The present article reviews the historical development of several collaborative care models between orthopaedic and geriatrics departments for the care of patients with hip fracture. Subacute orthogeriatric units are described and special emphasis is placed on geriatric consulting teams and acute orthogeriatric units, as well as on their benefits for the patient and the healthcare service. We also review evidence-based studies that support this type of care for patients with acute hip fracture and guidelines from scientific associations involved in the care of these patients. The cost of care is also analyzed. Lastly, the term "orthogeriatrics" is proposed as a common term for this activity and the need for improved future care is discussed.     

25(OH)D levels in diabetic pregnancies relation with neonatal hypocalcemia

The levels of 25(OH)D have been quantified in 42 insulin diabetic pregnancies (DP) through the three trimesters of pregnancy with a total of 177 determinations. In parallel we quantified this metabolite in 114 normal pregnant women (NP) and also in 116 normal controls (NC). In addition 25(OH)D was quantified in 18 (DP) and 19 (NP) at delivery in the 35-37th week of pregnancy, and ionic calcium was measured in their newborns at 24 h of life. Grouping by trimesters of gestation, the (NP) group had 25(OH)D levels similar to those of (NC) and none showed significant differences between trimesters of pregnancy. (DP) showed in all seasons lower (25(OH)D levels than (NC) but did not have differences in these levels between trimesters of pregnancy. The newborns of (DP) had lower ionic calcium levels than newborns of (NP). Eight newborns of (DP) had hypocalcemia and seven of their mothers showed 25(OH)D levels lower than 10 ng/ml. These findings suggest that lower 25(OH)D levels in (DP) can influence the neonatal hypocalcemia in their newborns.     

Anticuerpos antihipófisis en pacientes con sospecha de hipofisitis autoimmune

IntroductionDefinitive diagnosis of autoimmune hypophysitis (AH) is histological. However, a presumptive diagnosis can be made through clinical, biochemical and imaging data.ObjectiveThe objective of this study was to review the presence of antipituitary antibodies (APA) and antithyroid antibodies (ATA) in patients with suspected AH in order to determinate the utility of APA in the diagnosis of AH.Material and methodsWe studied 36 patients divided into seven groups according to the data suggesting AH (isolated corticotropin deficiency, other idiopathic pituitary deficiencies, idiopathic hyperprolactinemia, empty sella, sellar mass with thickened stalk, proven histological hypophysitis) or because of previous autoimmune endocrine diseases. Twenty-four controls without endocrinological disease were also included. In all subjects, APA were determined by immunofluorescence over primate pituitary gland and ATA by an agglutination technique.ResultsNone of the controls and only 9 patients, all of them women, were APA-positive. Of the 9 APA-positive patients, 43% belonged to the group of patients with isolated ACTH deficiency. In 8 patients, APA were determined again during the follow-up; 6 remained APA-negative, but one patient became APA-positive and another became APA-negative. ATA were positive in 12 patients, 22.2% of whom were also APA-positive, and in one control.ConclusionsThe prevalence of APA positivity among the study patients was low. These antibodies were found only in women, mostly with isolated corticotropin deficiency. APA and ATA coexisted in only 22% of the patients studied.     

Free [NADH]/[NAD(+)] regulates sirtuin expression

Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD⁺] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD⁺] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice.We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD⁺] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.