Alterations In Nitric Oxide Levels Research Articles

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman-Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho -0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho -0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho -0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho -0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.

Nitric Oxide Regulates the Ralstonia solanacearum Type III Secretion System.

Ralstonia solancearum causes bacterial wilt disease on diverse plant hosts. R. solanacearum cells enter a host from soil or infested water through the roots, then multiply and spread in the water-transporting xylem vessels. Despite the low nutrient content of xylem sap, R. solanacearum grows very well inside the host, using denitrification to respire in this hypoxic environment. R. solanacearum growth in planta also depends on the successful deployment of protein effectors into host cells via a type III secretion system (T3SS). The T3SS is absolutely required for R. solanacearum virulence, but it is metabolically costly and can trigger host defenses. Thus, the pathogen's success depends on optimized regulation of the T3SS. We found that a byproduct of denitrification, the toxic free-radical nitric oxide (NO), positively regulates the R. solanacearum T3SS both in vitro and in planta. Using chemical treatments and R. solanacearum mutants with altered NO levels, we show that the expression of a key T3SS regulator, hrpB, is induced by NO in culture. Analyzing the transcriptome of R. solanacearum responding to varying levels of NO both in culture and in planta revealed that the T3SS and effectors were broadly upregulated with increasing levels of NO. This regulation was specific to the T3SS and was not shared by other stressors. Our results suggest that R. solanacearum may experience an NO-rich environment in the plant host and that this NO contributes to the activation of the T3SS during infection. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Brassinosteroids interact with nitric oxide in the response of rice root systems to arsenic stress

Brassinosteroids (BRs), an emerging class of phytohormones, affect numerous plant physiological and metabolic processes and can improve plant defense systems to counteract metalloid phytotoxicity. Nitric oxide (NO), a reactive nitrogen species (RNS), behaves as a signalling molecule activating plant cellular responses to various environmental conditions. Brassinosteroids induce NO synthesis through nitrate reductase (NR) and NO synthase (NOS) activities. Arsenite and arsenate, inorganic forms of the metalloid arsenic (As), cause both soil pollution and many disorders in numerous plants, including important crops like rice, due to the oxidative stress generated by the imbalance between RNS and reactive oxygen species (ROS). Rice is very susceptible to As toxicity because both As availability and solubility are high in flooded paddy fields in many cultivated areas. The research aims to investigate the effects of BRs on the rice root systems exposed to 10-4 M Na2HAsO40.7 H2O [As(V)] or 2.5 × 10-5 M NaAsO2 [As(III)], highlighting the induced cyto-histological events and dissecting the NO role in the root response. A specific concentration (10-7 M) of 24-epibrassinolide (24-eBL), an exogenously applied BR, increases lateral root (LR) formation of more than 50% in the presence of As(III) or As(V). In addition, eBL attenuates the thickening of the cell walls induced by As in the outermost root cortical layers of LRs and in the adventitious roots (ARs) by reducing of ⁓ 50% the lignin deposition, while it restores the As(v)-altered NO levels by increasing OsNOS1 expression and the cellular NO distribution.

Evaluating the role of nitric oxide in myogenesis in vitro

Skeletal muscle injury activates satellite cells to proliferate as myoblasts and migrate, differentiate and fuse with existing fibres at the site of injury. Nitric oxide (NO), a free radical produced by NO synthase, is elevated and supports healing after in vivo injury. NOS-independent elevation of NO levels in vitro is possible via donors such as molsidomine (SIN-1). We hypothesized that alterations in NO levels may directly influence myogenic processes critical for skeletal muscle wound healing. This study aimed to clarify the role of NO in myoblast proliferation, migration and differentiation. Baseline NO levels were established in vitro, whereafter NO levels were manipulated during myogenesis using l-NAME (NOS inhibitor) or SIN-1. Baseline NO levels generated by myoblasts in proliferation media did not change 1 h after stimulation. Addition of a pro-proliferative dose of HGF slightly elevated NO levels 1 h post-stimulation, whereas cell numbers assessed 24 h later increased significantly; l-NAME reduced the HGF-driven increase in NO and proliferation, reducing wound closure over 16 h. In differentiation media, NO levels increased significantly within 24 h, returning to baseline over several days. Regular addition of l-NAME to differentiating cells significantly reduced NO levels and fusion. SIN-1 increased NO levels in a dose-dependent manner, reaching maximal levels 16 h post-treatment. SIN-1, added at 0, 2 and 4 days, significantly increased myofiber area (26 ± 1.8% vs 18.6 ± 3.4% in control at 5 day, p < 0.0001), without affecting proliferation or migration. In conclusion, this study demonstrates that, during skeletal muscle regeneration, increased NO specifically stimulates myoblast differentiation.

Abstract 14458: Plasma Gasotransmitter Levels in Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is associated with oxidative stress. Hydrogen sulfide and nitric oxide (NOx) are gasotransmitters involved in cardiovascular redox homeostasis. Free sulfide is increased in the plasma of human patients with atrial fibrillation. Although nitric oxide synthase expression and polymorphism has been studied in atrial fibrillation, NOx levels have not been measured in AF patients Hypothesis: AF is associated with altered NOx levels, and sulfide: nitrite ratio. Methods: Free NOx, total NOx, and nitrotyrosine levels were measured in patients without AF (n = 65), paroxysmal AF (PAF, n = 26) and persistent AF (n = 25) and compared between groups. Previously published sulfide levels from these patients were used to calculate free sulfide: total NOx ratio. Clinical characteristics of these patients were compared. Student’s t-test and nominal logistic regression were used for statistical analysis. Results: The patients without AF were younger but comparable to AF patients with regard to race, sex, diabetes, sleep apnea, and smoking history. Patients with AF were more likely to have hypertension (82% versus 54% non-AF patients, p = 0.002) and heart failure (47% versus 25% of non-AF, p = 0.02). On the other hand, non-AF patients were more likely to have coronary artery disease and/or peripheral arterial disease (43% versus 17% in patients with AF, p = 0.005). Compared to non-AF patients, AF patients had significantly lower total NOx (212 vs 268nM, p=0.005), free NOx (192 vs 237nM, p=0.039), and total sulfide: total NOx ratio (0.028 vs 0.020, p&lt;0.01). Compared to PAF patients, persistent AF patients had further significant reduction in total NOx (177 vs 243nM, p=0.04). At 3-month follow up, free NOx levels increased from baseline in patients who underwent successful conversion to normal sinus rhythm (n=11, p=0.048). Levels of oxidative stress marker, nitrotyrosine, trended higher in patients with AF compared to non-AF patients (1.10 vs 1.01 p=0.08). Multivariable logistic regression showed that total NOx was associated with AF independent of age, sex, race, HTN, DM and heart failure (OR per 10nM decrease in NOx= 1.04, CI=1.001-1.094, p=0.0471*) Conclusion: Reduced NOx levels and increased free sulfide to NOx ratio are associated with AF.

Associations Among Nitric Oxide and Enkephalinases With Fibromyalgia Symptoms.

Fibromyalgia (FM) is a complex syndrome of uncertain etiology, characterized by the presence of widespread pain. Both nitric oxide and enkephalinases modulate pain perception. The aim of this study was to evaluate the relationships among serum nitric oxide levels, oxytocinase activity, and enkephalin-degrading aminopeptidase (EDA) activity with pain-related clinical manifestations in women with FM. We performed an observational case study in a population of 58 women diagnosed with FM. Serum nitric oxide levels were analyzed by an ozone chemiluminescence-based assay. Both serum oxytocinase and EDA activities were fluorometrically determined. Pain threshold and pain magnitude were evaluated using the PainMatcher. The pressure pain thresholds were measured using a digital pressure algometer. We used a visual analog scale, the Central Sensitization Inventory, the Revised Fibromyalgia Impact Questionnaire, and the Beck Anxiety Inventory to assess the global level of pain, the symptoms associated with the central sensitization syndrome, the severity of FM, and the anxiety level, respectively. Multiple linear regression analysis adjusted by age, body mass index, and menopause status revealed significant associations between nitric oxide levels and dominant occiput pressure pain thresholds, nondominant occiput pressure pain thresholds, and FM effects. Significant associations of oxytocinase activity with the visual analog scale and dominant knee pressure pain thresholds were also found. Moreover, results showed a significant association between high EDA activity levels and dominant second-rib pressure pain thresholds. Our data have shown significant relationships of serum nitric oxide levels and oxytocinase and EDA activities with some body pressure pain thresholds, the daily activity level, and the global intensity of pain in women with FM. These results suggest that pain, which is the main symptom of this syndrome, may be related to alterations in nitric oxide levels and in oxytocinase and EDA activities in patients with FM.

Rejuvenated Circulating Endothelial Progenitor Cells and Nitric Oxide in Premenopausal Women with Hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

Wound with Diabetes: Present Scenario and Future.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by an increase in blood glucose level. Several factors, such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction, play a vital role in the pathogenesis of diabetes, which further leads to serious diabetic complications. The diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors, such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. The process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol, and fructose. Therefore, diabetic wound requires more time to heal as compared to the normal wound. Healing time is delayed in diabetic wound due to many factors, such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wounds includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents are also one way to manage the diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells.

Immunomodulatory and antiparasitic effects of garlic-arteether combination via nitric oxide pathway in Plasmodium berghei-infected mice.

Many reports indicate medicinal value of garlic (Allium sativum), a popular herbal medicine used worldwide, and its therapeutic effect against several diseases. Earlier studies in our laboratory have shown a potential therapeutic role of garlic-artemisinin combination in mice infected with Plasmodium berghei. A single dose of α, β-arteether with three oral doses of garlic provides almost 95% protection. The present study aims to understand the mode of action of this combination. We have documented the level of nitric oxide (NO), a key molecule of protection and have seen in the reversal of organ morphology caused by malaria infection. The combination effects on the (a) survival rate and degree of parasitemia and (b) NO levels in blood, liver, spleen and thymus of malaria-infected mice were investigated. During the study, liver, spleen and thymus cell suspensions were assessed for immunobiochemical alterations of NO levels. The increase in NO level after infection appears to be unable to protect, whereas striking increase in spleen and thymus leads to protection against infection, and is further confirmed by detection of increased inducible nitric oxide synthase mRNA expression levels in different organs by RT-PCR. In addition, the role of T cell subsets during combination treatment was also studied. All these results indicate a potential mechanism of protection through NO pathway in combination-treated animals after malaria infection and may lead to an immunotherapy trial of malaria disease.

The -786 T/C polymorphism of NOS3 gene is a susceptibility marker of COPD among Tunisians that correlates with nitric oxide levels and airflow obstruction

ObjectiveThe goal of this study was to examine the role of G894T (rs1799983), -786T/C (rs3918161) and a 27 bp variable number of tandem repeats (VNTR) 4B/4A of NOS3 gene on the risk and severity of COPD. MethodsThe study included 194 controls and 138 COPD patients. NOS3 G894T, -786T/C and 4B/4A variants were determined by PCR analysis based on the banding pattern on gel electrophoresis. Pulmonary function was evaluated using body plethysmography. The levels of nitric oxide, peroxynitrite and lipid peroxides (T-BARS) were determined using spectrophotometric methods. Levels of serum IL-6, TNF-α and TGFβ were determined by ELISA. ResultsIn case-control studies, both G894T and -786T/C variants were associated with COPD risk. A significantly increased risk of COPD was found with the NOS3894T and -786C alleles (OR:1.93, P=0.001; OR:2.05, P=0.001, respectively). No significant impact of the G894T and 4B/4A SNPs was found on COPD severity, while a significant correlation was retrieved between the NOS3 -786T/C variation and advanced stages (OR: 1.89, P=0.009). In addition, COPD patients with the -786CC genotype exhibited lower FEV1% values in comparison to -786TT carriers (48±3.28 vs. 58.06±2.3, P=0.01, respectively). Patients having the -786CC genotype presented lower plasma levels of nitric oxide and higher T-BARS in comparison to -786TT individuals (173.22±13.4 vs. 228.93±16.8, P=0.01; 1.8±0.15 vs. 1.22±0.15, P=0.01, respectively). ConclusionThis study provides the first evidence for the association of G894T, -786T/C variants with COPD risk among Tunisians. The -786T/C variation correlates with enhanced airflow limitation. This finding could be related to altered levels of nitric oxide and enhanced lipid peroxides among patients carrying the -786CC genotype.

L-arginine Protects Cardiac and Smooth Muscle Against Statin-Induced Myopathy

High dose statin therapy has been shown to negatively influence muscle function with reactive oxygen species, inflammation and nitric oxide levels as contributing mechanisms. Typically, skeletal muscle shows the most damage, however other muscle types may also be affected. This study aimed to assess the efficacy of L-arginine (L-arg) to protect cardiac and smooth muscle in an animal model of statin-induced myopathy (SIM). 10-12 week-old female Wistar (WIS) rats were randomly assigned to one of four treatment groups; control (CON), SIM (80 mg/kg/day of simvastatin), control + L-arg (L-arg; 100 mg/kg/day) and SIM + L-arg (SIM + L-arg). Treatment persisted for two weeks after which assessments of cardiac and smooth muscle function were made. The onset of SIM was associated with significant increases in left ventricular mass (WIS 2.45 m/gbwt; SIM 2.79 mg/gbwt), hydroxyproline content, alterations in nitric oxide levels and prolongation of cardiac action potential duration. The administration of L-arginine to SIM animals was noted to reduce left ventricular mass, hydroxyproline (SIM 6.65 mg/ml; SIM + L-arg 2.21 mg/ml) levels, restore nitric oxide concentration and prevent prolongation of action potentials. Notably the administration of high dose statin therapy improved endothelial dependent and independent vessel function which was further improved via L-arg co-therapy. These findings suggest high dose statin therapy enhanced vessel function but negatively impacted on left ventricular structure and function. Cardiac remodelling and sustained blood vessel function from SIM can be improved with L-arg co-therapy in young female rats.

Early stage of obesity potentiates nitric oxide reduction during the development of renal failure

Obesity is a serious health problem associated with the pathogenesis of various metabolic diseases. Nitric Oxide (NO) plays an important role in kidney function and altered NO levels have been associated with the pathogenesis of obesity. Therefore, we aimed to study whether an early stage of obesity contributes with progression of renal failure through further NO impairment. Male C57BL/6 mice were fed with a high-fat diet (HFD) or a normal diet (ND) during 2 weeks. All mice underwent either sham surgery (sham) or 5/6 nephrectomy (Np). One group of HFD Np mice was treated with antioxidants plus L-arginine. Kidney damage parameters were assessed and eNOS metabolism was evaluated. Mice on a HFD increased body weight, eNOS protein and mRNA expression, and radical oxygen species (ROS). Urine nitrites excretion, urine volume, and plasma BH4 were decreased. In HFD mice, 5/6 Np further increased BH2 and urine protein concentration, ROS levels, and eNOS mRNA expression. The decrease in BH4 plasma levels and urine nitrites excretion was accentuated. NO synthesis stimulation with the antioxidants + L-arginine treatment prevented all these changes. The early changes in NO metabolism are associated with an early stage of obesity. This effect on NO potentiates kidney damage development.

Tadalafil: A Phosphodiesterase‐5 Inhibitor for Benign Prostatic Hyperplasia

Tadalafil is a phosphodiesterase (PDE)-5 inhibitor recently approved by the United States Food and Drug Administration for lower urinary tracts symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). The mechanism for improved LUTS is thought to be related to three principal theories: alterations in nitric oxide levels, Rho-associated protein kinase deactivation, and reductions in pelvic atherosclerosis. The efficacy of PDE-5 inhibitors for the treatment of LUTS associated with BPH has been demonstrated in several randomized placebo-controlled trials. Tadalafil is thought to be superior based on an extended half-life; however, other PDE-5 inhibitors have positive results in BPH and have not been proved to be inferior to tadalafil. Before administration, concomitant use of medications such as nonselective α-adrenergic antagonists, nitrates, and cytochrome P450 inhibitors should be assessed for possible drug interactions. Potential adverse drug events seen in Food and Drug Administration-approved tadalafil include back pain, dyspepsia, headache, and dizziness. Given the efficacy and safety data currently available, the PDE-5 inhibitor tadalafil represents a reasonable alternative for selected male patients with LUTS associated with BPH, especially with concomitant erectile dysfunction.

Nitric oxide causes root apical meristem defects and growth inhibition while reducing PIN-FORMED 1 (PIN1)-dependent acropetal auxin transport

Nitric oxide (NO) is considered a key regulator of plant developmental processes and defense, although the mechanism and direct targets of NO action remain largely unknown. We used phenotypic, cellular, and genetic analyses in Arabidopsis thaliana to explore the role of NO in regulating primary root growth and auxin transport. Treatment with the NO donors S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and S-nitrosoglutathione reduces cell division, affecting the distribution of mitotic cells and meristem size by reducing cell size and number compared with NO depletion by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, genetic backgrounds in which the endogenous NO levels are enhanced [chlorophyll a/b binding protein underexpressed 1/NO overproducer 1 (cue1/nox1) mirror this response, together with an increased cell differentiation phenotype. Because of the importance of auxin distribution in regulating primary root growth, we analyzed auxin-dependent response after altering NO levels. Both elevated NO supply and the NO-overproducing Arabidopsis mutant cue1/nox1 exhibit reduced expression of the auxin reporter markers DR5pro:GUS/GFP. These effects were accompanied by a reduction in auxin transport in primary roots. NO application and the cue1/nox1 mutation caused decreased PIN-FORMED 1 (PIN1)-GFP fluorescence in a proteasome-independent manner. Remarkably, the cue1/nox1-mutant root phenotypes resemble those of pin1 mutants. The use of both chemical treatments and mutants with altered NO levels demonstrates that high levels of NO reduce auxin transport and response by a PIN1-dependent mechanism, and root meristem activity is reduced concomitantly.

Inhibition of ketamine-induced hyperlocomotion in mice by the essential oil of Alpinia zerumbet: possible involvement of an antioxidant effect

The antipsychotic, hypnotic, myorelaxant and antioxidant effects of the essential oil of Alpinia zerumbet (EOAZ) were studied. EOAZ (50, 100 and 200 mg/kg i.p.) was administered once to mice for the determination of antipsychotic activity (evaluated by ketamine-induced hyperlocomotion), hypnotic activity (induced by sodium pentobarbital, 40 mg/kg i.p.), motor coordination (rotarod test), antioxidant effects (determination of lipid peroxidation and GSH levels), as well as alterations in nitric oxide levels (determination of nitrite content). EOAZ at doses of 100 and 200 mg/kg prevented ketamine hyperlocomotion, as did haloperidol (0.2 mg/kg i.p). EOAZ at a dose of 200 mg/kg decreased sleep latency, while all doses increased sleeping time. There was no effect on motor coordination. The in-vitro antioxidant capacity of the oil caused a decrease in lipid peroxidation and increase in GSH levels. EOAZ also prevented the decrease in nitrite content caused by oxidative stress. The results suggest antipsychotic and antioxidant effects for the EOAZ that may have promising efficacy for the treatment of schizophrenia.

Role of nitric oxide in placental vascular development and function

Nitric oxide (NO) is one of the most pleiotropic signaling molecules at systemic and cellular levels, participating in vascular tone regulation, cellular respiration, proliferation, apoptosis and gene expression. Indeed NO actively participates in trophoblast invasion, placental development and represents the main vasodilator in this tissue. Despite the large number of studies addressing the role of NO in the placenta, its participation in placental vascular development and the effect of altered levels of NO on placental function remains to be clarified. This review draws a time-line of the participation of NO throughout placental vascular development, from the differentiation of vascular precursors to the consolidation of vascular function are considered. The influence of NO on cell types involved in the origin of the placental vasculature and the expression and function of the nitric oxide synthases (NOS) throughout pregnancy are described. The developmental processes involved in the placental vascular bed are considered, such as the participation of NO in placental vasculogenesis and angiogenesis through VEGF and Angiopoietin signaling molecules. The role of NO in vascular function once the placental vascular tree has developed, in normal pregnancy as well as in pregnancy-related diseases, is then discussed.

Neonatal ventral hippocampus lesion induces increase in no levels which is attenuated by subchronic haloperidol treatment

Haloperidol is a potent dopamine receptor antagonist and used to treat psychotic disorders, such as schizophrenia. Recent clinical and preclinical studies demonstrated the overactivity of the nitric oxide (NO) system in schizophrenia. Neonatal ventral hippocampal (nVH) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Here, we investigate first whether the nVH lesion causes changes in NO levels in different limbic brain regions in young adults, postnatal day (PD) 81, and second, whether haloperidol treatment from PD60 to PD81 reverses these changes, by determining the accumulation of nitrites. The results show that NO levels at the level of the prefrontal cortex, occipital cortex, and cerebellum are higher in the nVH lesion animals, and that the haloperidol, in part, attenuates these altered NO levels. The NO levels observed in the nVH lesion animals with and without haloperidol treatment may be relevant to behaviors observed in schizophrenia.

Endothelial nitric oxide synthase gene intron 4 polymorphism predicts new onset diabetes mellitus after transplantation in kidney allograft recipients treated with cyclosporin A

Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle. Polymorphisms of the eNOS gene have been associated with altered eNOS activity and NO levels. Although several factors have been demonstrated for new onset diabetes mellitus after transplantation (NODAT), determining a genetic susceptibility for all patients requires further study. In our study, we evaluated the relationship between eNOS gene intron 4 polymorphism and NODAT in kidney allograft recipients. A total of 82 consecutive patients who received their first kidney transplantation and maintained graft function for at least a 12-month post-transplant period and who used triple therapy including cyclosporin A (CsA) for maintenance immunosuppression were included. PCR-RFLP was used for genetic analyses. Nine of 82 patients (11%) developed NODAT. Concerning the prevalence of eNOS intron 4 gene polymorphism, a significantly higher percentage of 4a allele carriers developed NODAT than non-carriers [6/26 (23.1%) versus 3/56 (5.4%), P = 0.02]. Compared with non-diabetics, NODAT patients were older (P = 0.04), had higher rate of hepatitis C (P < 0.05) and higher body mass index at the time of transplantation (P = 0.03). In regression analyses, having a 4a allele of the eNOS gene intron 4 polymorphism (P = 0.02) and HCV seropositivity (P = 0.03) were found to be independent risk factors for the development of NODAT. These findings suggest that carrying a 4a allele of the eNOS gene intron 4 polymorphism is associated with NODAT. This may help us to further understand the individual risk for development of NODAT in kidney allograft recipients under CsA treatment.

Cerebral Malaria: A Vasculopathy

Cerebral Malaria: A Vasculopathy

Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk

The aim of this study was to investigate total antioxidant (TAC), and oxidant capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical mastitis. Brown Swiss and Holstein breed cows were screened with California Mastitis Test (CMT) to determine mammary glands with subclinical mastitis. Moreover, somatic cell counts (SCC) were determined electronically in all milk samples. Mammary quarters were classified as healthy (n=25) or subclinical mastitis (n=35) based on CMT scores and somatic cell count (SCC: < or =200,000/ml or >200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly higher (p<0.001, p<0.005 and p<0.001, respectively) in milk from mammary quarters with subclinical mastitis compared to those from healthy mammary quarters. In conclusion, subclinical mastitis results in higher NO concentrations, TOC and SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in NO levels and TOC in milk could be used as an alternative diagnostic tool to screen for subclinical mastitis.