Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans

BackgroundExcessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress.Objective and methodsWe explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes.ResultsThe levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro.ConclusionsThese data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly.     

Outcomes of emergency surgery for acute abdomen in dialysis patients: experience of a single community hospital

Purpose

Long-term dialysis often causes physiological and metabolic problems that may affect the outcomes of surgery. The aim of this study was to elucidate whether emergency surgery for acute abdomen yields similar outcomes in dialysis patients versus non-dialysis patients.

Methods

The subjects were 126 patients who underwent emergency surgery for acute abdomen between January, 2007 and November, 2011 in our hospital. They were divided into a dialysis group (HD group; n = 9) and a non-dialysis group (non-HD group; n = 117) and their postoperative morbidity and mortality were compared.

Results

Postoperative morbidity and mortality were significantly worse in the HD group. All 9 of these patients succumbed to postoperative complications versus only 5 of the 117 patients in the non-HD group.

Conclusion

The outcomes of emergency surgery for acute abdomen were significantly worse for dialysis patients than for non-dialysis patients. Prompt diagnosis, initiation of the most suitable surgical procedure, and meticulous postoperative cares are imperative to improving the surgical outcomes of dialysis patients.     

Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist,pranlukast, in Japanese patients with moderate asthma

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.     

Optical mapping of pontine chemosensitive regions of neonatal rat

We analyzed the neuronal response to hypercapnic acidosis, using an optical recording technique with a fluorescent voltage-sensitive dye (di-4-ANEPPS), in pontine slice preparations of neonatal rats, containing the locus coeruleus (LC), which has been electrophysiologically demonstrated to be chemosensitive. The dye-stained preparation was continuously superfused with artificial cerebrospinal fluid. Epifluorescence of the slice was detected using a high-sensitivity optical recording system. Changes in the intensity of fluorescence were serially analyzed while switching artificial cerebrospinal fluid from control to hypercapnic acidosis, or vice versa. The optical recording method revealed that the LC, as reported in previous studies, reversibly showed a depolarizing response to hypercapnic acidosis in 56% of the examined preparations. The A5 area (56%) also exhibited a reversible, depolarizing response to hypercapnic acidosis. The response was preserved under conditions in which chemical synaptic transmission was blocked by low Ca(2+)-high Mg(2+) solution. These results suggest that the optical recording method is applicable to identification of potentially chemosensitive areas, which deserve further electrophysiological analysis, and that the A5 area could be chemosensitive.     

Arthrographic findings in hemiplegic shoulders

To discover the influence of hemiplegia on arthrographic changes in hemiplegic shoulders, we compared arthrographic findings from paralyzed and nonparalyzed shoulders in 77 patients with hemiplegia. The correlation between arthrographic changes in paralyzed shoulders and characteristics of the hemiplegic condition was also investigated. Hemiplegic changes were considered to be responsible for adhesive changes in affected shoulders because those changes were found in paralyzed shoulders at a statistically significant higher rate (54.6%) than in the nonparalyzed side (32.5%). The occurrence rate of contrast leakage from capsule tear on the subscapular bursa and the bicipital tendon sleeve was higher on the nonparalyzed side than on the paralyzed side. It is suggested that capsular contracture due to hemiplegia prohibits capsular tear during arthrographic maneuvers. No significant difference was found in the occurrence of rotator cuff tear between the paralyzed and the nonparalyzed shoulder. Those changes on the paralyzed side were not correlated with any characteristics of hemiplegics except for shoulder pain prior to the onset of hemiplegia.