Impact of systemic inflammatory response syndrome and surgical Apgar score on post-operative acute kidney injury.

BACKGROUND: Surgical Apgar Score (SAS) is relatively weakly associated with post-operative outcomes in emergency surgery, compared with elective surgery. A combination of systemic inflammatory response syndrome (SIRS) and SAS may be useful for prediction of poor outcomes after emergency surgery. METHODS: A retrospective study was conducted in patients who underwent emergency abdominal or cerebral surgery from January 2005 to December 2010. AKI was diagnosed using Acute Kidney Injury Network criteria for 2 days after surgery. Pre-operative SIRS was defined as SIRS score ≥ 2. Patients were divided into those with SAS ≥ 5 and < 5. Independent risk factors for post-operative AKI were identified. Ability to predict post-operative AKI was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Of 742 patients, 175 (24%) had post-operative AKI. Pre-operative SIRS (OR 1.9, 95% CI: 1.2-2.9, P < 0.01) and SAS < 5 (OR 2.6, 95% CI: 1.7-4.1, P < 0.01) were independent risk factors for post-operative AKI. Patients without SIRS and SAS < 5 had an increased risk of post-operative AKI (odds ratio (OR) 3.6, 95% confidence interval (CI) 1.9-6.7, P < 0.01) and those with SIRS and SAS < 5 had increased risks of post-operative AKI (OR 5.9, 95% CI: 3.7-9.3, P < 0.01) and hospital mortality (OR 3.5, 95% CI: 1.9-6.3, P < 0.01). In ROC analysis, the c-statistic using both SIRS and SAS < 5 was 0.81 (95% CI: 0.77-0.84, P < 0.01) and higher than without use of these factors (P < 0.01). CONCLUSION: Pre-operative SIRS and SAS are independently associated with post-operative AKI. Simultaneous use of pre-operative SIRS and SAS may improve prediction of poor post-operative outcomes.

Home blood pressure measurements associated with better blood pressure control: the J-HOME study.

The usefulness of self-measurements of blood pressure (BP) at home (home BP measurements) in hypertensive patients has been reported by many studies. Several national guidelines recommend the use of home BP measurements to achieve better hypertension control. The objective of this study was to clarify the association between home BP measurements and hypertension treatment among 2363 essential hypertensive patients taking antihypertensive drugs. Compared to the 543 (23.0%) patients who had not taken home BP measurements, the 1820 (77.0%) patients who had taken home BP measurements were significantly older, included a higher proportion of males, included a higher proportion with a family history of hypertension, took a greater number of antihypertensive drugs and alpha blockers and took antihypertensive drugs more often in the evening. Home BP measurements were associated with significantly better control of home and office BP levels. Compared to patients who had not taken home BP measurements, the adjusted odds ratios for good control of morning home BPs, evening home BPs and office BPs in patients who had taken home BP measurements were 1.46 (95% confidential interval (CI) 1.33-1.57), 1.35 (95% CI 1.21-1.47) and 1.23 (95% CI 1.06-1.37), respectively. Home BP measurements were associated with good hypertensive management. Our findings suggest that it is important that physicians recommend home BP measurements to their patients.

Chemiluminescence as an index of drug-induced free radical production in pancreatic islets.

Chemiluminescence induced in isolated islets from rat pancreas by the diabetogenic drugs, alloxan and streptozotocin, has been measured. The assay system consisted of 3 microM of luminol, 10 islets, and 100 microM of alloxan or 500 microM of streptozotocin in 5 ml Krebs-Ringer bicarbonate buffer containing 16 mM of Hepes (pH 7.4). Alloxan-induced chemiluminescence appeared very rapidly and lasted more than 5 min. On the other hand, streptozotocin failed to produce chemiluminescence over a period of 60 min after addition. The presence of superoxide dismutase (1000 U/ml) and/or catalase (100 U/ml) markedly suppressed alloxan-induced chemiluminescence. These results suggest that alloxan acts as an exogenous free radical generator in pancreatic islets, but that streptozotocin does not. The involvement of superoxide anion and hydrogen peroxide in production of chemiluminescence by alloxan suggests that the hydroxyl radical may mediate this chemiluminescence.

Alloxan-induced free radical production in isolated cells. Selective effect on islet cells.

Chemiluminescence, as a direct measure of oxygen free radical production, induced in isolated cells, hepatocytes, and red cells by the action of alloxan has been measured. The assay system used luminol, 3 microM, for signal amplification. The buffer used was Krebs-Ringer bicarbonate with 16 mM Hepes, pH 7.4. This buffer did not react with alloxan in the absence of cells. Some chemiluminescence was noted from all cells in the absence of alloxan. In the presence of alloxan, reactions occurred within seconds and islet cells were significantly more reactive to alloxan than either red cells or hepatocytes as defined by alloxan dose-response curves with fixed cell numbers or fixed surface areas. These data indicate a cell specificity for an early action of alloxan perhaps mediated at the cell membrane.

Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection.

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.

Living situations associated with poor dietary intake among healthy Japanese elderly: the Ohasama Study.

BACKGROUND: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. OBJECTIVE: To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. METHODS: The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. RESULTS: In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. CONCLUSION: These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.

Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement.

This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American "C" family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule-associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single-site GCC to GTC substitution at codon 4 (Ala4 --> Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with Ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.

Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism.

This study was designed to determine if peroxidation of biomembrane lipid and the protective system can be modified by the change in oxidative metabolism induced by thyroid dysfunction. The free radical scavengers (i.e. cuprozinc cytosolic and mangano mitochondrial superoxide dismutases, glutathione peroxidase, and catalase), mitochondrial oxidative marker enzymes (cytochrome c oxidase and fumarase), and lipid peroxide were measured in liver, heart, soleus (slow oxidative), and extensor digitorum longus (fast glycolytic) muscles. Rats were rendered hyper- or hypothyroid for 4 weeks and then killed. Superoxide dismutases were detected by specific RIAs: catalase by polarography, and lipid peroxide by fluorimetry. Hypothyroid rats failed to grow, while hyperthyroid rats had hypertrophied hearts but no growth failure. An increase in lipid peroxide was observed in the soleus and heart muscles of hyperthyroid rats. This was accompanied by an increase in mitochondrial superoxide dismutase and oxidative markers. No such change was observed in either fast glycolytic muscle or liver. Glutathione peroxidase decreased in all tissues of hyperthyroid rats, and there was a parallel decrease in catalase in most tissues. On the other hand, hypothyroidism induced a reduction in oxidative markers and mitochondrial superoxide dismutase in heart and skeletal muscles, but only a marginal change in lipid peroxidation. The cytosolic superoxide dismutase did not change in relation to either oxidative metabolism or lipid peroxidation. These results suggest that the enhanced oxidative metabolism and decreased glutathione peroxidase in hyperthyroidism result in an increase in lipid peroxidation and, in slow oxidative and heart muscle, possible organ damage. No adverse reaction mediated by active oxygen species was found in hypothyroid rat tissues.

Oxidative muscular injury and its relevance to hyperthyroidism.

In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical-mediated injury.

Antioxidants in the serum of children with insulin-dependent diabetes mellitus.

To determine whether alteration in serum antioxidant status is related to the increased oxidative stress as a cause of diabetic angiopathy, we measured both the antioxidant activity (AOA) and total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in serum of children with insulin-dependent diabetes mellitus (IDDM). The AOA was measured as the ability to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, transferrin, and albumin as components of AOA; and ascorbic acid, uric acid, protein sulfhydryl, and alpha-tocopherol as components of TRAP. Serum AOA appeared to be decreased in the diabetics in relation to poor glycemic control, corresponding to the decrease in transferrin and albumin. Serum haptoglobin level was also decreased in the diabetics. Similarly, the directly measured TRAP value was decreased in the diabetic serum mainly due to the decreased contribution of unidentified chain-breaking antioxidants, despite the increase in ascorbic acid and alpha-tocopherol. The decrease in both types of antioxidant activity in the diabetic serum, as new findings, suggests that a defective serum antioxidant status contributes to the increased oxidative stress in IDDM.

Effect of selenium deficiency on cellular and extracellular glutathione peroxidases: immunochemical detection and mRNA analysis in rat kidney and serum.

To determine the effect of selenium (Se) deficiency on expression of glutathione peroxidase (GSH-Px) 1 and 2, we measured GSH-Px activity in rat serum, liver and kidneys, serum immunoreactive GSH-Px 2, and the mRNAs of kidney GSH-Px 1 and 2. We purified rat GSH-Px 2 and raised polyclonal antibodies. Immunoreactive GSH-Px 2 was measured by rocket immunoelectrophoresis. GSH-Px 2 was purified 1470-fold with a specific activity of 250 units/mg. Immunoblotting detected only GSH-Px 2 in rat serum, and much less GSH-Px 2 than GSH-Px 1 in kidney. Immunoblot signal of kidney GSH-Px 1 and 2 decreased progressively in Se deficient rats. Serum GSH-Px activity in Se deficient rats at 1, 2, 3, and 4 weeks declined to 33, 20, 10, and 9% of the control, while the serum level of immunoreactive GSH-Px 2 was 58, 24, 15, and 10% of the control, suggesting the presence of an inactive protein at week 1. GSH-Px activity declined to 4 and 11% of the control in the liver and kidney at 4 weeks. The mRNAs of kidney GSH-Px 1 and 2 showed similar decreases, and were 24 and 23% of the control at 4 weeks. GSH-Px mRNA levels were better preserved than GSH-Px activity, suggesting that GSH-Px expression was regulated at both pre-translational and translational levels.

Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents.

To determine whether oxidant-antioxidant balance is altered in chronic renal failure, antioxidant enzymes and lipid peroxide in peripheral blood cells and lipid peroxide in plasma were measured. Nine children and adolescents maintained on hemodialysis (HD), 9 on continuous ambulatory peritoneal dialysis (CAPD), and 14 controls were studied. Lipid peroxide was assayed fluorimetrically as thiobarbituric acid-reactive substances, superoxide dismutases by radioimmunoassays. Both manganese and copper-zinc superoxide dismutases in lymphocytes and monocytes in the HD and CAPD patients, and manganese superoxide dismutase in polymorphs in the HD patients were higher than in the controls. Copper-zinc superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes were unaltered. The lipid peroxide level in plasma in the dialyzed patients was increased, whereas those in polymorphs and lymphocytes were unaltered. Triglyceride and total cholesterol in plasma in the dialyzed patients were also increased. The plasma lipid peroxide in the patients correlated with the triglyceride and total cholesterol level. This is the first study in which manganese superoxide dismutase is measured in nucleated cells of the patients with chronic renal failure. The present results suggest that increased superoxide dismutases protect against oxidative stress induced by chronic renal failure in nucleated cells but in neither erythrocytes nor plasma.

Increased plasma cholesteryl ester transfer activity in obese children.

To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo Al were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo Al. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.

Development of a sandwich enzyme-linked immunosorbent assay for the determination of human heart type fatty acid-binding protein in plasma and urine by using two different monoclonal antibodies specific for human heart fatty acid-binding protein.

We have developed a sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human heart type fatty acid-binding protein (H-FABP) in human plasma and urine using the combination of two distinct monoclonal antibodies (MAbs) directed against human H-FABP purified from human heart muscle. The total assay time of the ELISA is practically much shorter than that of the competitive enzyme immunoassay (EIA) we previously reported. The immunoreactive mass of human H-FABP was specifically measured using a horseradish peroxidase (HRPO)-labeled anti-human H-FABP MAb as an enzyme-linked MAb, and anti-human H-FABP MAb immobilized on the polystyrene microtiter plate as a solid-phase MAb, and purified human H-FABP as standard materials. The assay range of the ELISA was 0-250 ng/ml of plasma and urine. The ELISA yielded a coefficient of variation of less than 10% in inter- and intra-assays, and the good linearity was obtained in dilution test using clinical samples. Anticoagulants, except sodium fluoride and a high concentration of hemoglobin and bilirubin, did not interfere with the assay of plasma samples. A high concentration of hemoglobin, bilirubin and immunoglobulin, and contamination with seminal plasma did not interfere with the assay of urine samples. The average recovery of purified human H-FABP added to human plasma and urine samples was 98.5% and 97.0%, respectively. Myoglobin and myosin did not crossreact in the ELISA. The minimum detection limit of the ELISA was 1.25 ng/ml. The immunoreactive masses of human H-FABP in plasma and urine samples, obtained from one hundred normal healthy subjects were quantified by the sandwich ELISA. The normal mean (+/- SD) level of human H-FABP mass in plasma was 3.65 +/- 1.81 ng/ml, and that in urine was 3.20 +/- 2.70 ng/ml. In conclusion, this sandwich ELISA is a useful tool for the sensitive and precise determination of human H-FABP in human plasma and urine, and it may be used specifically for clinical investigation and diagnosis of myocardial injury.

Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues.

We investigated the developmental profile of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in tissue sections obtained from fetal (Day 12 to 21 of gestation) and neonatal (Day 0 and 6) rats. Tissues were stained immunohistochemically with specific antisera against the respective rat SODs. There was a general trend towards richness of SODs in the epithelial linings and metabolically active sites, although differential distribution between the two SODs also existed. At Day 12 of gestation, immunoreactivity for both SODs was detected in the cardiomyocytes but not in other tissues. Hepatocytes expressed CuZnSOD at Day 14 and MnSOD at Day 17. By Day 18 CuZnSOD was detected in the epithelial cells of the gastrointestinal tract, respiratory tract, pancreatic islets, kidneys, and adrenals. These tissues exhibited MnSOD staining at Day 19. CuZnSOD occurred in the epithelia of the thyroid, thymus, and salivary glands at Day 19, while MnSOD was seen at Day 21. The increase in intensity of the staining for SODs occurred no later than postnatal Day 0, indicating that most tissues accumulated SODs during late gestation. Breathing atmospheric oxygen during early extrauterine life did not appreciably intensify the SOD staining. These results suggest that perinatal increase in SODs occurs as a general mechanism of preparation for birth.

Evaluation of systemic inflammatory response syndrome criteria as a predictor of mortality in emergency patients transported by ambulance.

Based on the concept of the systemic inflammatory response syndrome (SIRS), a one year retrospective study was carried out to examine SIRS criteria as a simple and rapid predictor of outcome for emergency patients. Among a total of 2,180 patients transported to the emergency room by ambulance, 318 (14.8%) had primary SIRS and 389 (17.8%) met SIRS criteria at some point during the entire treatment period. The admission rate for primary SIRS increased sequentially as more SIRS criteria were met, rising from 15.4% in non-SIRS to 100% when all four criteria were met. The mortality of primary SIRS also increased sequentially as more SIRS criteria were met, rising from 1.4% in non-SIRS to 35.3% when all four criteria were met. Furthermore, heart rate, C-reactive protein and platelet count were considered to be potentially useful new criteria for a group of SIRS patients with a high risk of mortality (high-risk SIRS), based on a comparison of variables between SIRS patients who died and SIRS patients who survived. The mortality associated with primary SIRS increased sequentially as more high-risk SIRS criteria were met, rising from 7.6% when none were met to 50.0% when two criteria were met. Considering the high specificity of primary SIRS for admission (89.5%) and mortality (86.8%), SIRS criteria have clinical and prognostic importance in the management of emergency patients. Given the high mortality (29.9%), the new high-risk SIRS criteria may also be useful as entry criteria for clinical trials of innovative therapies for patients with SIRS.

Unilateral upregulation of cyclooxygenase-2 following cerebral, cortical photothrombosis in the rat: suppression by MK-801 and co-distribution with enzymes involved in the oxidative stress cascade.

Cyclooxygenase-2 (COX-2) is an essential enzyme for prostaglandin synthesis from arachidonic acid, during which considerable amounts of superoxide are produced. During pathological conditions, superoxide and nitric oxide (NO) rapidly form peroxynitrite, a potent cytotoxin, causing symptoms referred to as oxidative stress response. Superoxide is controlled by enzymes such as manganese- or copper-zinc-dependent superoxide dismutase (Mn-SOD, CuZn-SOD), glutathione peroxidase (GPx) and antioxidants derived from heme oxygenase (HO) activity such as biliverdin and bilirubin. NO derives from 3 NO-synthases (NOS I-III) from which the calcium-dependent NOS-I and III are activated rapidly due to hyperexcitation. We studied the induction of COX-2 by immunohistochemistry at days 1, 2 and 5 following cortical photothrombosis in normal and MK-801 treated rats. The results showed a weak constitutive, neuronal expression of COX-2 in cortex and amygdala. Layers II+III contained considerably more COX-2 than infragranular layers. One and 2 days following injury COX-2 was highly upregulated in the supragranular layers of the whole injured hemisphere compared with sham-operated animals and compared to the contralateral unlesioned hemisphere, whereas at day 5 COX-2 levels had returned to baseline. MK-801 treatment caused a reduction in COX-2 upregulation at day one and by day 2 no significant differences between injured and contralateral hemisphere were measurable. COX-2 positive neurons were found in close association with NOS-I containing neurons and their fibers but were not colocalized. In addition, codistribution of COX-2 was found with HO-1, CuZn-SOD and GPx containing cells, whereas COX-2 was colocalized with HO-2 and/or MnSOD in cortical neurons.

Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology.

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.

Growth-hormone-induced changes in postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities.

A comparison of treated and untreated patients with growth hormone deficiency revealed that administration of growth hormone reduced lipoprotein lipase and hepatic lipase activities, total cholesterol, and high-density lipoprotein cholesterol concentrations. The possible significance of these results is discussed.

Increased Cu/Zn superoxide dismutase-like immunoreactivity in the swollen axons of rats intoxicated chronically with beta,beta'-iminodipropionitrile.

Demonstration of a genetic linkage between the Cu/Zn superoxide dismutase (SOD1) gene and familial amyotrophic lateral sclerosis (ALS) has aroused interest in the role of SOD1 in spinal motoneuronal death. We used chronically beta,beta'-iminodipropionitrile (IDPN)-intoxicated rats as a model of ALS and investigated SOD1 changes in the spinal cord by immunocytochemical and in situ hybridization techniques. Compared with control rats, SOD1-like immunoreactivity (SOD1-IR) increased in swollen axons of the proximal spinal roots, but not in motoneuronal and dorsal root ganglion neuronal cell bodies where SOD1 gene transcription did not increase. The present data indicate that treatment with IDPN induces accumulation of SOD1 in the swollen axons by blocking slow axonal flow, suggesting the possibility that increased SOD1-IR in ALS is induced by axonal flow blockade.