Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial.

OBJECTIVE: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of nitric oxide (NO) supplementation to the CPB circuit on the development of cardiac surgery-associated AKI. METHODS: This prospective randomized controlled study included 96 patients with moderate risk of renal complications who underwent elective cardiac surgery with CPB. The study protocol was registered at ClinicalTrials.gov (identifier NCT03527381). Patients were randomly allocated to either NO supplementation to the CPB bypass circuit (NO treatment group; n = 48) or usual care (control group; n = 48). In the NO treatment group, 40-ppm NO was administered during the entire CPB period. The primary outcome was the incidence of AKI. RESULTS: NO treatment was associated with a significant decrease in AKI incidence (10 cases [20.8%] vs 20 cases [41.6%] in the control group; relative risk, 0.5; 95% confidence interval, 0.26-0.95; P = .023) and a higher median urine output during CPB (2.6 mL/kg/h [interquartile range (IQR), 2.1-5.08 mL/kg/h] vs 1.7 mL/kg/h [IQR, 0.80-2.50 mL/kg/h]; P = .0002). The median urinary neutrophil gelatinase-associated lipocalin level at 4 hours after surgery was significantly lower in the NO treatment group (1.12 ng/mL [IQR, 0.75-5.8 ng/mL] vs 4.62 ng/mL [IQR, 2.02-34.55 ng/mL]; P = .005). In the NO treatment group, concentrations of NO metabolites were significantly increased at 5 minutes postclamping, at 5 minutes after declamping, and at the end of the operation. Concentrations of proinflammatory and anti-inflammatory mediators and free plasma hemoglobin did not differ significantly between the 2 groups. CONCLUSIONS: NO administration in patients at moderate risk of renal complications undergoing elective cardiac surgery with CPB was associated with a lower incidence of AKI.

Reaction of endogenous Coenzyme Q10 with nitrogen monoxide and its metabolite nitrogen dioxide.

Objectives: Coenzyme Q10, incorporated in DOPC lyposomes or naturally present in liver bovine mitochondria or in human blood plasma, was reacted with nitrogen dioxide •NO2 or with a •NO/•NO2 mixture. Methods and Results: The reaction course was monitored by Electron Paramagnetic Resonance (EPR) spectroscopy and in all cases the formation of a di-tert-alkyl nitroxide was observed, deriving from the addition of •NO2 to one of the double bonds, most likely the terminal one, of the isoprenic chain. The rate constant for nitroxide formation was also determined by EPR spectroscopy and an initial rate of ca. 7 × 10-8 M s-1 was obtained.

CC16 Levels into Adult Life Are Associated with Nitrogen Dioxide Exposure at Birth.

Rationale: Lung function and growth are adversely associated with nitrogen dioxide (NO2) exposure. Lower levels of circulating club cell secretory protein (CC16) in childhood are also associated with subsequent decreased lung function. NO2 exposure may induce epithelial damage in lungs and alter club cell proliferation and morphology.Objectives: To determine if increased ambient NO2 levels at participants' home addresses in early life were associated with decreased levels of CC16 from age 6 to 32 years.Methods: Participants were enrolled at birth in the Tucson Children's Respiratory Study and had circulating CC16 measured at least once between age 6 and 32. Linear mixed models were used to determine the association between estimated ambient NO2 exposure at participants' home address at birth or age 6 with CC16 levels from age 6 to 32.Measurements and Main Results: NO2 exposures at birth or age 6 were available for 777 children with one or more CC16 measurement. We found a negative association between NO2 exposure and CC16 levels, with a 4.7% (95% confidence interval, -8.6 to -0.7) decrease in CC16 levels from age 6 to 32 per interquartile range increase in NO2 exposure (6.0 ppb) at the participants' birth address. We observed modification by race (p interaction = 0.04), with stronger associations among participants with at least one black parent (-29.6% [95% confidence interval, -42.9% to -13.2%] per interquartile range). NO2 at participant's age 6 address was not significantly associated with CC16 levels (-1.9%; 95% confidence interval, -6.3 to 2.6).Conclusions: Higher exposure to NO2 at birth is associated with persistently low levels of CC16 from 6 to 32 years.

Impaired skin barrier function in mice with colon carcinoma induced by azoxymethane and dextran sodium sulfate.

We have previously reported that impaired skin barrier function was induced by small intestinal injury in mice. Therefore, we postulated that other intestinal diseases might also influence skin barrier function. In this study, we evaluated the skin barrier function of hairless mice with colon carcinoma that was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). In mice treated with these drugs, we observed elevated transepidermal water loss and reduced skin hydration levels, compared to those in the control mice. In addition, plasma nitrogen di/trioxide (NO2(-)/NO3(-)) levels were significantly elevated, and expression of type I collagen was significantly reduced in the treated mice, compared to those in control. These results suggest that impaired skin barrier function occurs in mice when colon carcinoma is present.

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium-induced colitis mouse model.

Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.

The relationship between plasma and salivary NOx.

Several studies have shown that fasting plasma nitrite (NO2(-)) is an indicator of endothelial nitric oxide synthase (NOS) activity while plasma nitrate (NO3(-)) or the sum of NO2(-) and NO3(-) (NOx) does not reflect NOS function. Plasma NO2(-) can also be elevated through dietary NO3(-) where the NO3(-) is partially reduced to NO2(-) by oral bacteria and enters the plasma through the digestive system. NO3(-) is taken up from plasma by salivary glands and the cycle repeats itself. Thus, one may propose that salivary NO2(-) is an indicator of plasma NO2(-) and consequently of NO production. Many brands of nitric oxide (NO) saliva test strips have been developed that suggest that their product is indicative of circulatory NO availability. However, data supporting a relationship between salivary and plasma NO2(-) or NO bioavailability are lacking. Here we have measured basal salivary and plasma NO2(-) and NO3(-) to determine if any correlation exists between these in 13 adult volunteers. We found no significant correlation between basal salivary and plasma NO2(-). Also no correlation exists between salivary NO3(-) and plasma NO2(-). However, we did see a correlation between salivary NO3(-) and plasma NO3(-), and between salivary NO2(-) and plasma NO3(-). In a separate study, we compared the efficiency of salivary NO3(-) reduction with the efficacy of increasing plasma NO3(-) and NO2(-) after drinking beet juice, a high NO3(-)-containing beverage, in 10 adult volunteers. No significant correlation was observed between the ex vivo salivary reduction of NO3(-) to NO2(-) and plasma increases in NO3(-) or NO2(-). These results suggest that measures of salivary NO3(-), NO2(-) or NOx are not good indicators of endothelial function. In addition, the efficiency of saliva to reduce NO3(-) to NO2(-)ex-vivo does not demonstrate one's ability to increase plasma NO2(-) following consumption of dietary NO3(-).

Evaluation of oxidant-antioxidant status in oral toxicity of fish oil methyl esters and diesel fuel in male rats.

This study was conducted to compare the effects of oral toxicity induced by fish oil biodiesel and diesel fuel. Diesel and fish oil biodiesel were administered by oral gavage to rats. For this purpose, 35 rats were divided into five groups. Sunflower oil of 250 mg kg(-1) was administered to the rats in the control group by oral gavage. The rats in the D250 and D500 groups were administered by oral gavage 250 mg kg(-1) and 500 mg kg(-1) of diesel fuel dissolved in equal amounts of sunflower oil, respectively. The rats in the F250 and F500 groups were administered by oral gavage 250 mg kg(-1) and 500 mg kg(-1) of fish oil biodiesel dissolved in equal amounts of sunflower oil, respectively. At the end of the study, malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in the whole blood; catalase (CAT) activity level was measured in erythrocytes; and nitrite (NO2) and nitrate (NO3) levels were measured in the serum. It was observed that the whole blood MDA levels of the diesel groups were considerably different from those in the control and fish oil biodiesel groups (p < 0.001). GSH levels in the control group were observed to be considerably different from those in all other groups (p < 0.001). Serum NO3 concentrations in the diesel groups were found to be considerably different from those in the control and biodiesel groups. Serum NO2 concentrations in one of the diesel groups were significantly different from those in the control and biodiesel groups (p < 0.01 and p < 0.05, respectively). The CAT activity of the control group was observed to be different from that in the other groups. According to these results, both fish oil biodiesel and diesel fuel are thought to cause lipid peroxidation. It was observed that fish oil biodiesel does not induce as much oxidative damage as does the diesel fuel. It is suggested that fish oil biodiesel should be preferred as an alternative to the diesel.

Locally derived traffic-related air pollution and fetal growth restriction: a retrospective cohort study.

BACKGROUND: Fetal growth restriction has been inconsistently associated with maternal exposure to elevated levels of traffic-related air pollution. OBJECTIVE: We investigated the relationship between an individualised measure of fetal growth and maternal exposure to a specific marker for traffic-related air pollution. METHODS: We estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO2) during pregnancy for 23,452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with small for gestational age and sex (SGA) and fetal growth restriction, defined as proportion of optimal birth weight (POBW) below the 10th percentile. Sub-populations investigated were: women who spent most time at home, women who did not move house, women with respiratory or circulatory morbidity, women living in low/middle/high socio-economic areas, women who delivered before 37 weeks gestation, and women who delivered from 37 weeks gestation. RESULTS: An IQR increase in traffic-related air pollution in the second trimester across all women was associated with an OR of 1.31 (95% CI 1.07 to 1.60) for fetal growth restriction. Effects on fetal growth restriction (low POBW) were highest among women who subsequently delivered before 37 weeks of gestation. Effects on SGA were highest among women who did not move house: OR 1.35 (95% CI 1.08 to 1.69). CONCLUSIONS: Larger effect sizes were observed for low POBW than for SGA. Exposure to traffic-related air pollution in mid to late pregnancy was associated with risk of SGA and low POBW in this study.

Impairment of endothelial protection by ischemic postconditioning in patients with major depressive disorder.

This study used a model of ischemia-reperfusion injury to the brachial artery endothelium to investigate whether the protective role of ischemic postconditioning (IPostC) is impaired in patients with major depressive episode. Flow-mediated dilation (FMD) was measured before and after ischemia-reperfusion in the absence or presence of IPostC in 24 patients with major depressive disorder and 20 healthy controls. In addition, the severity of the depression, as assessed by the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) scores, and plasma nitrogen dioxide (NO(x)) levels were also determined. Ischemia-reperfusion resulted in a significant decrease in FMD in both patients with a major depressive episode and healthy controls. IPostC effectively prevented this decrease in FMD in healthy controls, but not in patients with a major depressive episode. HDRS and BDI scores were markedly increased, but plasma NO(x) levels decreased, in patients with a major depressive episode compared with those in healthy controls. Correlation analysis showed that HDRS and BDI scores and plasma NO(x) levels were significantly associated with post-ischemia-reperfusion FMD. These results suggest that endothelial protection by IPostC is impaired in patients with major depressive disorder, which may be related to the decrease in endothelial nitric oxide production and the severity of the depression.

A dynamic view of trauma/hemorrhage-induced inflammation in mice: principal drivers and networks.

BACKGROUND: Complex biological processes such as acute inflammation induced by trauma/hemorrhagic shock/ (T/HS) are dynamic and multi-dimensional. We utilized multiplexing cytokine analysis coupled with data-driven modeling to gain a systems perspective into T/HS. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subjected to surgical cannulation trauma (ST) ± hemorrhagic shock (HS; 25 mmHg), and followed for 1, 2, 3, or 4 h in each case. Serum was assayed for 20 cytokines and NO(2) (-)/NO(3) (-). These data were analyzed using four data-driven methods (Hierarchical Clustering Analysis [HCA], multivariate analysis [MA], Principal Component Analysis [PCA], and Dynamic Network Analysis [DyNA]). Using HCA, animals subjected to ST vs. ST + HS could be partially segregated based on inflammatory mediator profiles, despite a large overlap. Based on MA, interleukin [IL]-12p40/p70 (IL-12.total), monokine induced by interferon-γ (CXCL-9) [MIG], and IP-10 were the best discriminators between ST and ST/HS. PCA suggested that the inflammatory mediators found in the three main principal components in animals subjected to ST were IL-6, IL-10, and IL-13, while the three principal components in ST + HS included a large number of cytokines including IL-6, IL-10, keratinocyte-derived cytokine (CXCL-1) [KC], and tumor necrosis factor-α [TNF-α]. DyNA suggested that the circulating mediators produced in response to ST were characterized by a high degree of interconnection/complexity at all time points; the response to ST + HS consisted of different central nodes, and exhibited zero network density over the first 2 h with lesser connectivity vs. ST at all time points. DyNA also helped link the conclusions from MA and PCA, in that central nodes consisting of IP-10 and IL-12 were seen in ST, while MIG and IL-6 were central nodes in ST + HS. CONCLUSIONS/SIGNIFICANCE: These studies help elucidate the dynamics of T/HS-induced inflammation, complementing other forms of dynamic mechanistic modeling. These methods should be applicable to the analysis of other complex biological processes.

Recombinant human erythropoietin ameliorated endothelial dysfunction and macrophage infiltration by increasing nitric oxide in hypertensive 5/6 nephrectomized rat aorta.

Recombinant human erythropoietin (rHuEPO), used clinically for renal anemia, reportedly exhibits pleiotropic properties in various tissues. To test whether it ameliorates vascular injury, rHuEPO (75U/kg) was administered subcutaneously every 3days for 10days to 5/6 nephrectomized hypertensive rats (5/6Nx) treated with 1% NaCl. rHuEPO had no effect on increased systolic blood pressure or decreased hematocrit values, but normalized levels of proteinuria and creatinine clearance. Vasodilation in response to acetylcholine in the aortic ring was impaired in the 5/6Nx, and improved by treatment with rHuEPO. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of osteopontin were enhanced in the 5/6Nx aorta and the overexpression was suppressed by rHuEPO. rHuEPO also attenuated medial hyperplasia. Akt signaling was activated by the increased expression of phosphorylated Akt and GSK-3ß in aorta from rHuEPO-treated 5/6Nx. rHuEPO restored plasma NOx (NO(2)(-)+NO(3)(-)) levels and endothelial nitric oxide synthase (eNOS) content in the 5/6Nx aorta. Treatment with an eNOS substrate, l-arginine, which caused a similar increase in plasma NOx levels as the rHuEPO treatment, resulted in a normalization of endothelial dysfunction and vascular inflammation. These results suggest that a low dose of rHuEPO exerted vasoprotective effects in rats with hypertensive renal failure.

Air pollution, blood pressure, and the risk of hypertensive complications during pregnancy: the generation R study.

Exposure to air pollution is associated with elevated blood pressure and cardiovascular disease. We assessed the associations of exposure to particulate matter (PM(10)) and nitrogen dioxide (NO(2)) levels with blood pressure measured in each trimester of pregnancy and the risks of pregnancy-induced hypertension and preeclampsia in 7006 women participating in a prospective cohort study in the Netherlands. Information on gestational hypertensive disorders was obtained from medical records. PM(10) exposure was not associated with first trimester systolic and diastolic blood pressure, but a 10-µg/m(3) increase in PM(10) levels was associated with a 1.11-mm Hg (95% confidence interval [CI] 0.43 to 1.79) and 2.11-mm Hg (95% CI 1.34 to 2.89) increase in systolic blood pressure in the second and third trimester, respectively. Longitudinal analyses showed that elevated PM(10) exposure levels were associated with a steeper increase in systolic blood pressure throughout pregnancy (P<0.01), but not with diastolic blood pressure patterns. Elevated NO(2) exposure was associated with higher systolic blood pressure levels in the first, second, and third trimester (P<0.05), and with a more gradual increase when analyzed longitudinally (P<0.01). PM(10) exposure, but not NO(2) exposure, was associated with an increased risk of pregnancy-induced hypertension (odds ratio 1.72 [95% CI 1.12 to 2.63] per 10-µg/m(3) increase). In conclusion, our results suggest that air pollution may affect maternal cardiovascular health during pregnancy. The effects might be small but relevant on a population level.

Pre-emptive anti-hyperalgesic effect of electroacupuncture in carrageenan-induced inflammation: role of nitric oxide.

Central sensitization theory has been defined as pivotal for understanding the excitability changes in central neurons following peripheral inflammation or neuropathic injury. Considerable evidence has demonstrated that activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and subsequent nitric oxide (NO) production are the key in these changes. Consequently, neuromodulator drugs have been developed during the last decades. The electroacupuncture (EA) that acts as biochemical modulator in the spinal horn cord would prevent these changes. The aim of this study was to determine the thermal anti-hyperalgesic effect of EA (10 Hz, 3 mA) and its combination with L-NAME as nitric oxide synthase (NOS) inhibitor in carrageenan-induced hyperalgesia in rats. Also, it investigated the changes in the plasmatic concentrations of NO metabolites. Moreover, the EA combination with sub-effective dose of ketamine as a NMDA antagonist was tested. The EA pre-treatment conducted in unsedated, unrestrained and conscious animals showed a thermal anti-hyperalgesic effect in correspondence with plasmatic increase of NO metabolites. The L-NAME (30 mg/kg) pre-administration decreased significantly the plasmatic concentrations of NO(2)(-)/NO(3)(-) and suppressed the anti-hyperalgesic effect of EA. The combination of EA with ketamine enhanced the anti-hyperalgesic effect. These data constitute the first report that suggested the participation, at least in part, of the L-arginine-NOS-NO-GMPc pathway activation in anti-hyperalgesic effect of EA in carrageenan-induced inflammation model.

Thrombotic markers in metabolic syndrome subjects exposed to diesel exhaust.

Traffic-derived particulate matter (PM) is associated with cardiovascular morbidity and mortality, but the mechanism of this association is unclear. Prothrombotic processes have been linked to PM in epidemiological and animal models, but have not been consistently implicated in controlled human models. Diesel exhaust (DE) is a major contributor to PM. We conducted a controlled human exposure of DE in subjects with metabolic syndrome. The study objective was to evaluate DE exposure effects on prothrombotic markers in a population vulnerable to cardiovascular disease. A randomized, crossover, double-blinded design was used: 16 subjects with metabolic syndrome exposed on 3 different days (> or = 2 wk washout) to DE at 0 (filtered air, FA), 100 microg PM(2.5)/m(3) (DE(100)) and 200 mug PM(2.5)/m(3) (DE(200)). We assessed DE-associated changes in D-dimer, von Willebrand factor (VWF), and plasmin activator inhibitor-1 (PAI-1) at 3, 7, and 22 h after exposure initiation. A DE(200)-attributable decrease (1.17-fold; CI 1.04 to 1.34) in VWF was noted at 7 h. Significant changes did not occur in other primary endpoints. As previously noted with healthy subjects, strong diurnal patterns in PAI-1 were observed. Thus, in a novel study, we were unable to demonstrate a prothrombotic effect of moderate-dose diesel exhaust exposure in a population at risk for cardiovascular disease.

Dietary supplementation with laminarin, a fermentable marine beta (1-3) glucan, protects against hepatotoxicity induced by LPS in rat by modulating immune response in the hepatic tissue.

We tested the hypothesis that laminarin (LAM), a beta (1-3) polysaccharide extracted from brown algae, can modulate the response to a systemic inflammation. Male Wistar rats (n=7 per group) were fed a standard diet (control) or a diet supplemented with LAM for 25 days (5% during 4 days followed by 10% during 21 days). Thereafter, Escherichia coli lipopolysaccharides (LPS; 10 mg/kg i.p.) were injected and the animals were sacrificed 24 h after LPS challenge. The hypothermia, hyperglycemia and hypertriglyceridemia occurring early after LPS administration were less pronounced in LAM-treated rats than in controls. The increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities - reflecting hepatic alterations - was lessened after LPS injection in LAM-treated rats compared to control rats. LAM treatment decreased serum monocytes number, nitrite (NO2) and tumor necrosis factor-alpha (TNF-alpha). LAM also modulated intra-hepatic immune cells: it lowered the occurrence of peroxidase-positive cells (corresponding to monocytes/neutrophils) and, in contrast, it increased the number of ED2-positive cells, corresponding to resident hepatic macrophages, i.e. Kupffer cells. In conclusion, the hepatoprotective effect of marine beta (1-3) glucan during endotoxic shock may be linked to its immunomodulatory properties. We propose that both lower recruitment of inflammatory cells inside the liver tissue and lower secretion of inflammatory mediators play a role in the tissue protective effect of LAM. These effects could be due to a direct effect of beta-glucan on immune cells, or to an indirect effect through their dietary fibre properties (fermentation in the gut).

[Indices of antioxidant system of blood in differential diagnosis of obliterating atherosclerosis and obliterating thromboangiitis of the lower limbs].

The work was aimed at elucidating the role of the indices of the antioxidant system (AOS) of the blood and nitrogen oxide content in differential diagnosis of atherosclerosis obiiterans (AO) and thromboangiitis obiiterans (TO) of the lower extremities. Presented herein are the findings of examining a total of one hundred and thirteen 30-to-45-year-old patients (of these, 60 had TO and 53 had AO) with various level of occlusion (from the femoropoplietal segment to the aortoiliac zone) and the stage of chronic arterial insufficiency (CAI IIA-IV). The control group was composed of 30 apparently healthy age-matched male subjects. Besides the clinical, laboratory and special instrumental methods of study, we determined the parameters of the AOS of blood and the content of nitrogen oxide degradation products. It was determined that the directedness and pronouncedness of deviations in the parameters of the AOS and nitrogen oxide from the physiological norm depended on not only the aetiology of the disease involved, but on the degree of tissue hypoxia predetermined by the stage of CAI of the lower limbs. For differential diagnosis between AO and TO, the most informative should be considered the coefficient: SOD activity/catalase activity, index of peroxide-luminol-dependent chemiluminescence and the content of nitrogen oxide degradation products.

[Study of immunoglobulins, proinflammatory cytokines, lymphoproliferation and phagocytosis in peripheral blood of healthy young people exposed to different levels of atmospheric pollution]. / Estudio de inmunoglobulinas, citocinas proinflamatorias, linfoproliferación y fagocitosis en sangre periférica de jóvenes sanos expuestos a diferentes niveles de contaminación atmosférica.

BACKGROUND: Urban environmental pollutants, resulting from the inadequate control in the industries and from the use of vehicles, still represent a great danger for millions of people all around the world. PATIENTS AND METHOD: We made a study in healthy young people without family history of atopy that lived in Guadalajara's downtown, as well as in another group of young people who lived in a rural area. According to the census of the year 2000, Guadalajara city has a population of 4 million habitants, and a vehicle number of about a million. The immunological parameters that we studied were: IgG, IgA and IgM immunoglobulins by nephelometry, serum levels of proinflammatory cytokines IL-6, IL-1alpha, IL1-beta and TNF-alpha by ELISAs test, and the phagocytic index in polymorphonuclears. The atmospheric parameters were: NO2, O3, SO2, CO and the suspended particles that were less than 10 micrometers (PM10). These parameters were obtained from a mobile unit found at the Instituto de Astronomia y Meteorología de la Universidad de Guadalajara, and from an automatic station of environmental monitoring. RESULTS: It stands out the high concentrations of NO2 and PM10, which in several occasions were over the standards established by the WHO. IgG, IgA and IgM immunoglobulins were lower in the subjects living in the city that in those who lived in the rural area. Phagocytic index in polymorphonuclears, as well as IL-1alpha levels were higher in the city group, though we did not find a significant difference in the immunological parameters analyzed in the studied groups. CONCLUSION: Environmental pollution levels found at Guadalajara's downtown does not modify the immunological parameters studied in the peripheral blood of healthy young people. This shows that this group of population is less vulnerable than others to the exposition of moderate levels of urban air pollution.

Persistent HIV-1 replication does not explain low levels of T-cell interferon-gamma mRNA and elevated serum NO(2) (-)/NO(3) (-) in patients with stable CD4 T-cell responses to HAART.

HIV-1 infected patients adherent to HAART and displaying stable increases in CD4 T-cell counts differ in their control of HIV replication and one might expect this to reflect depressed immune function. The importance of virological control in functional immune reconstitution was investigated in HIV-1 infected patients who maintained high or undetectable plasma HIV RNA levels over 2-4 years on HAART (discordant and complete responders, respectively). Immunocompetence and immune activation were assessed directly ex vivo and after a short period of culture, as HIV replication in cultures from viraemic patients may artificially depress responses. Expression of cytokine (interferon-gamma, interleukin-5) and chemokine receptor (CCR5, CRTH2) mRNA were determined and soluble CD30 and NO(2) (-)/NO(3) (-) were measured in sera. Unstimulated cells from all patients had low levels of IFNgamma mRNA relative to uninfected controls. Discordant responders had more IFNgamma, IL-5 and CCR5 mRNA in mitogen-stimulated PBMC than complete responders, where the difference could be attributed to CD8-T-cells. Serum NO(2) (-)/NO(3) (-) levels were significantly higher in all patients than controls, with no difference between complete and discordant responders. Serum CD30 levels were significantly higher in discordant responders. These data indicate a persistent immune deficit in immune reconstituted patients irrespective of HIV viral load and associate persistent viral replication with lymphocyte activation, probably involving CD8 T-cells.

[Effects of nebivolol on serum levels of NO2 and NO3 oxides in patients with type 2 diabetes mellitus]. / Vplyv nebivololu na riven' metabolitiv oksydu azotu NO2 ta NO3 v syrovattsi krovi khvorykh na tsukrovyi diabet typu 2.

In patients with type 2 diabetes mellitus, we used nevibolol, a lipophilic high-selective beta 1-blocker. It has been found out that the drug, while augmenting the synthesis of nitrogen oxide, improves antioxidant properties. Therefore, it can be recommended for use in patients with type 2 diabetes mellitus concurrent with arterial hypertension to achieve normalization of arterial pressure and accomplish a correction of endothelial dysfunction.