Emerging threat of Eimeria operational taxonomic units (OTUs) on poultry production.

Coccidiosis is an antagonistic poultry disease which negatively impacts animal welfare and productivity. The disease is caused by an obligate, intracellular protozoon known as Eimeria. Several Eimeria species known to infect chickens have been well documented. However, recent studies have elucidated the emergence of three novel genetic variants or operational taxonomic units (OTUs). The discovery of OTUx, OTUy and OTUz complicates the identification and diagnosis of coccidiosis. OTUs are clusters of unknown or uncultivated organisms that are grouped according to a similarity in DNA sequence to a set of specific gene markers. OTUs have been reported in the Earth's Southern Hemisphere, including Australia, Venezuela, India, Zambia, Uganda, Tanzania, China and Ghana. Elucidating their impact on the poultry industry is fundamental in preventing anticoccidial resistance and to access the potential of OTUs as vaccine candidates to provide cross-protection against similar Eimeria species. The identification of OTUs further decreases the risk of false negative coccidial diagnosis. Therefore, this article reviews the importance and risk imposed by OTUs, coupled with their prevalence and geographical distribution in chickens globally.

A review of Eimeria antigen identification for the development of novel anticoccidial vaccines.

Coccidiosis is a major poultry disease which compromises animal welfare and costs the global chicken industry a huge economic loss. As a result, research entailing coccidial control measures is crucial. Coccidiosis is caused by Eimeria parasites that are highly immunogenic. Consequently, a low dosage of the Eimeria parasite supplied by a vaccine will enable the host organism to develop an innate immune response towards the pathogen. The production of traditional live anticoccidial vaccines is limited by their low reproductive index and high production costs, among other factors. Recombinant vaccines overcome these limitations by eliciting undesired contaminants and prevent the reversal of toxoids back to their original toxigenic form. Recombinant vaccines are produced using defined Eimeria antigens and harmless adjuvants. Thus, studies regarding the identification of potent novel Eimeria antigens which stimulate both cell-mediated and humoral immune responses in chickens are essential. Although the prevalence and risk posed by Eimeria have been well established, there is a dearth of information on genetic and antigenic diversity within the field. Therefore, this paper discusses the potential and efficiency of recombinant vaccines as an anticoccidial control measure. Novel protective Eimeria antigens and their antigenic diversity for the production of cheap, easily accessible recombinant vaccines are also reviewed.

Chicken anemia virus: A deadly pathogen of poultry.

Chicken infectious anemia (CIA) is an immunosuppressive disease that causes great economic loss in poultry industry globally. This disease is caused by chicken anemia virus (CAV), an icosahedral and single-stranded DNA virus that is transmitted both vertically and horizontally. CAV, which belongs to the genus Gyrovirus has been reported in human, mouse and dog feces. Rapid identification of different strains of gyrovirus with high similarity to CAV has heightened public concern on this virus. Clinical symptoms of this disease such as intramuscular hemorrhage, weight loss, anemia and bone marrow aplasia are prominent in young chickens, while adult chickens experience subclinical symptoms. Biosecurity measures such as good management practice and vaccination have been the most reliable control strategy against this virus. Therefore, this study reviews the current state of CAV under the following subheadings (i) Chicken anemia virus (ii) Pathogenesis of CAV (iii) Serological evaluation of host antibodies to CAV (iv) Association of Marek's disease and infectious bursa disease with CAV infection (v) Genetic diversity and phylogenetics of CAV strains (vi) Current and future vaccine strategy in the control of CAV. In conclusion, improvement on DNA and recombinant vaccines strategy could curtail the economic impact of CAV on poultry birds. Keywords: adjuvant; CAV; chicken; disease.

Use of discriminant analysis for the evaluation of coccidiosis resistance parameters in chickens raised in hot humid tropical environment.

Coccidiosis endemicity remains a major challenge in poultry production in the tropics and all over the world. In order to develop predictive tool for identification of chickens that are at risk of coccidiosis among Nigerian indigenous chickens, body weight gain (BWG) and hematological variables were determined for chickens infected with Eimeria tenella (female = 60, male = 63) and uninfected (female = 51, male = 45). The hematological variables analyzed include the following: packed cell volume (PCV, %), white blood cells (WBC, × 106/µl), and red blood cells (RBC, × 106/µl), as well as differential leucocyte percentages of neutrophils, lymphocytes, monocytes, and eosinophils. Body weight gain was determined at days 3, 6, 9, 12, and 15. Of the 12 variables analyzed, BWG at day 3, monocyte, PCV, and WBC in males and BWG at days 6, 9, and 12, PCV, and WBC in female chickens showed significant (P ≤ 0.01) difference between the infected and uninfected. Stepwise discriminant analysis evolved a model that could distinguish uninfected from Eimeria-infected chickens. Packed cell volume, WBC, BWG at day 3, and lymphocytes emerged the most discriminant between uninfected and Eimeria-infected chickens in male chickens. In female chickens, PCV, RBC, and BWG at day 3 were identified as most discriminant variables in separating the uninfected from Eimeria-infected chickens. Therefore, this study suggests that routine blood test and estimates of body weight gain could serve as a useful tool for identifying chickens that may be at risk of coccidiosis, enabling improvement of preventive measures.

Dengue virus specific Immunoglobulin G antibodies among patients with febrile conditions in Osogbo, Southwestern Nigeria.

Dengue fever is becoming one of the major public health problems in the world and its distribution has been premised on the migration of people from infected regions. This study was carried out to determine the prevalence of dengue virus IgG antibody among the patients with febrile conditions attending health facilities in Osogbo metropolis, Southwestern Nigeria. The blood samples collected between July and September, 2014 were tested for Plasmodium falciparum and the sera were subsequently subjected to Enzyme Linked Immunosorbent Assay (ELISA) to detect the dengue virus IgG antibody. Of the hundred consented participants screened, 77% were sero-positive for dengue virus IgG antibody while 41% were positive for P. falciparum. Thirty-three (33%) of the participants were positive for both dengue virus IgG antibody and P. falciparum. No significant difference was found in the prevalence of dengue virus IgG antibody and malaria among the participants (P>0.05). The high prevalence of dengue virus IgG and malaria signifies the need by the government of Osun State to sensitize residents and institute urgent measures to mitigate the resultant effects of morbidity and mortality due to dengue fever and dengue hemorrhagic fever which has hitherto appeared to be alien to the area.

Dengue virus specific Immunoglobulin G antibodies among

Dengue fever is becoming one of the major public health problems in the world and its distribution has been premised on the migration of people from infected regions. This study was carried out to determine the prevalence of dengue virus IgG antibody among the patients with febrile conditions attending health facilities in Osogbo metropolis, Southwestern Nigeria. The blood samples collected between July and September, 2014 were tested for Plasmodium falciparum and the sera were subsequently subjected to Enzyme Linked Immunosorbent Assay (ELISA) to detect the dengue virus IgG antibody. Of the hundred consented participants screened, 77% were sero-positive for dengue virus IgG antibody while 41% were positive for P. falciparum. Thirty-three (33%) of the participants were positive for both dengue virus IgG antibody and P. falciparum. No significant difference was found in the prevalence of dengue virus IgG antibody and malaria among the participants (P>0.05). The high prevalence of dengue virus IgG and malaria signifies the need by the government of Osun State to sensitize residents and institute urgent measures to mitigate the resultant effects of morbidity and mortality due to dengue fever and dengue hemorrhagic fever which has hitherto appeared to be alien to the area.

Effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of turkeys, hatchability of eggs and post-hatch growth of their offsprings.

The effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of breeder turkeys, hatchability of eggs and post-hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of L-carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm L-carnitine showed the lowest (p < 0.01) plasma total cholesterol (TC) and low-density lipoprotein concentration (LDL). Breeder hens offered 50 ppm L-carnitine with no regard to application mode recorded the highest (p < 0.01) plasma high-density lipoprotein (HDL). Hens offered 50 and 100 ppm L-carnitine irrespective of application mode also showed reduced (p < 0.01) egg-yolk TC concentration at 32 weeks of age. Dietary supplementation of 50 ppm L-carnitine for breeder turkeys recorded the lowest (p < 0.01) egg-yolk triglyceride (TG) at 40 weeks of age. Hens offered 50 ppm L-carnitine irrespective of application mode recorded the highest (p < 0.05) hen-day egg production. Incidence of dead-in-shell also reduced (p < 0.05) with increasing dosage of L-carnitine. Dietary supplementation of 50 ppm and oral application in drinking water of 100 ppm L-carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with L-carnitine recorded no post-hatch mortality. Highest (p < 0.05) post-hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm L-carnitine. In conclusion, dietary supplementation of 50 ppm L-carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead-in-shell, egg-yolk cholesterol and resulted in improved post-hatch growth performance.

Epidemiological evaluation of onchocerciasis along Ogun River System, southwest Nigeria.

BACKGROUND & OBJECTIVE: Epidemiological studies were carried out to assess the prevalence and community microfilarial load (CMFL) of onchocerciasis after repeated annual treatment with ivermectin along Ogun river System, southwest Nigeria. METHOD: Skin snips were taken from consented participants in 11 selected communities along the River system. The microfilarial load of the community was estimated. RESULTS: The prevalence and CMFL varied significantly in the communities (p <0.05). The prevalence of onchocerciasis ranged from 19.1 to 45.6%, while the CMFL ranged from 0.11 to 1.03 microfilariae per skin snip. The CMFL recorded was <5 microfilariae per skin snip, i.e. recognized by WHO as threshold value in certifying the communities to be free of onchocerciasis as public health problem, thus, signifying the possibility of onchocerciasis elimination in the study area. CONCLUSION: Efforts should therefore be intensified to achieve improved ivermectin coverage and compliance in annual ivermectin treatment in order to completely eliminate onchocerciasis as a public health problem in the studied communities.

Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats.

OBJECTIVE: We compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance. METHODS: Female Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods. RESULTS: There was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3±0.09, 0.82±0.08; p<0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17±0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3±0.15, 1.11±0.12) was significantly higher than controls (0.56±0.13; p<0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65. CONCLUSION: We conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.

The Rho kinase inhibitor azaindole-1 has long-acting vasodilator activity in the pulmonary vascular bed of the intact chest rat.

Responses to a selective azaindole-based Rho kinase (ROCK) inhibitor (azaindole-1) were investigated in the rat. Intravenous injections of azaindole-1 (10-300 µg/kg), produced small decreases in pulmonary arterial pressure and larger decreases in systemic arterial pressure without changing cardiac output. Responses to azaindole-1 were slow in onset and long in duration. When baseline pulmonary vascular tone was increased with U46619 or L-NAME, the decreases in pulmonary arterial pressure in response to the ROCK inhibitor were increased. The ROCK inhibitor attenuated the increase in pulmonary arterial pressure in response to ventilatory hypoxia. Azaindole-1 decreased pulmonary and systemic arterial pressures in rats with monocrotaline-induced pulmonary hypertension. These results show that azaindole-1 has significant vasodilator activity in the pulmonary and systemic vascular beds and that responses are larger, slower in onset, and longer in duration when compared with the prototypical agent fasudil. Azaindole-1 reversed hypoxic pulmonary vasoconstriction and decreased pulmonary and systemic arterial pressures in a similar manner in rats with monocrotaline-induced pulmonary hypertension. These data suggest that ROCK is involved in regulating baseline tone in the pulmonary and systemic vascular beds, and that ROCK inhibition will promote vasodilation when tone is increased by diverse stimuli including treatment with monocrotaline.

Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.

Peroxynitrite has potent pulmonary vasodilator activity in the rat.

Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses.

Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase activator, BAY 60-2770, are not dependent on endogenous nitric oxide or reduced heme.

4-({(4-Carboxybutyl)[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}methyl)benzoic acid (BAY 60-2770) is a nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC) that increases the catalytic activity of the heme-oxidized or heme-free form of the enzyme. In this study, responses to intravenous injections of the sGC activator BAY 60-2770 were investigated under baseline and elevated tone conditions induced by the thromboxane mimic U-46619 when NO synthesis was inhibited by N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), when sGC activity was inhibited by 1H-[1,2,4]-oxadizaolo[4,3]quinoxaline-1-one (ODQ), an agent that oxidizes sGC, and in animals with monocrotaline-induced pulmonary hypertension. The intravenous injections of BAY 60-2770 under baseline conditions caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and no change or small increases in cardiac output. Under elevated tone conditions during infusion of U-46619, intravenous injections of BAY 60-2770 caused larger decreases in pulmonary arterial pressure, smaller decreases in systemic arterial pressure, and increases in cardiac output. Pulmonary vasodilator responses to BAY 60-2770 were enhanced by L-NAME or by ODQ in a dose that attenuated responses to the NO donor sodium nitroprusside. ODQ had no significant effect on baseline pressures and attenuated pulmonary and systemic vasodilator responses to the sGC stimulator BAY 41-8543 2-{1-[2-(fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5(4-morpholinyl)-4,6-pyrimidinediamine. BAY 60-2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats in a nonselective manner. The present data show that BAY 60-2770 has vasodilator activity in the pulmonary and systemic vascular beds that is enhanced by ODQ and NOS inhibition, suggesting that the heme-oxidized form of sGC can be activated in vivo in an NO-independent manner to promote vasodilation. These results show that BAY 60-2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats, suggesting that BAY 60-2770 does not have selective pulmonary vasodilator activity in animals with monocrotaline-induced pulmonary hypertension.

Molecular approaches to the identification of Bulinus species in south-west Nigeria and observations on natural snail infections with schistosomes.

The current study considers the distribution of a small sample of 138 Bulinus snails, across 28 localities within eight Nigerian states. Snails were identified using a combination of molecular methods involving both DNA sequencing of a partial cytochrome oxidase subunit 1 (cox1) fragment and restriction profiles obtained from ribosomal internal transcribed spacer (its) amplicons. The results showed that the majority of Bulinus samples tested belonged to the species Bulinus truncatus while only two were Bulinus globosus. The use of RsaI restriction endonuclease to cleave the ribosomal its of Bulinus, as a method of species identification, was adopted for the majority of samples, this being a quicker and cheaper method better suited to small laboratory environments. Polymerase chain reaction (PCR) amplification of the schistosome Dra1 repeat within each of the collected Bulinus samples was employed to determine the extent and distribution of infected snails within the sample areas. Successful amplification of the Dra1 repeat demonstrated that 29.7% of snails were infected with schistosomes. Sequencing of the partial schistosome its from a small subset of snail samples suggested that some snails were either penetrated by both Schistosoma haematobium and Schistosoma bovis miracidia or hybrid miracidia formed from the two species.

Growth performance of Nigerian local chickens in crosses involving an exotic broiler breeder.

Six-hundred-and-seven-day-old chicks were generated from Nigerian local chickens consisting of three genotypes (Normal-feathered; Frizzled-feathered; Naked neck) and an exotic broiler breeder (Anak Titan) to evaluate growth performance for possible meat-type chicken development. Growth parameters measured were body weight, breast girth and keel length on weekly basis for 20 weeks. Effects of sire, dam and chick genotypes were significant (P<0.001) on growth traits. At week 20, chickens sired by the Anak Titan weighed 1,614.82 g followed by Normal-feathered local chickens with body weight of 1,211.32 g. Progenies of Anak Titan and Naked neck dams weighed 1,761.96 and 1,292.80 g at week 20, respectively. Among purebreds, Anak Titan weighed 35.05 g at day-old and had heaviest body weight of 2,360.29 g at 20 weeks compared to the three local strains. The average body weights for the crossbred, Normal-feathered × Anak Titan at day-old and week 20 were 36.39 and 1,577.63 g, respectively. This was followed by Anak Titan × Naked neck with 33.32 g at day-old and 1,514.14 g at week 20. Sex had significant effect (P<0.05) at weeks 16 and 20 with the males having higher mean values than their female counterparts. This study revealed that crosses involving Anak Titan sire × Naked neck dam had highest growth performance, and there was no strain differences among the growth performance of purebred Nigerian local chickens.

Urinary schistosomiasis transmission in Epe, an urban community of Southwest Nigeria.

BACKGROUND: A survey of Schistosoma haematobium infection in Epe, an urban community in Lagos State, Southwest Nigeria, was carried out to ascertain the possibility that schistosomiasis, otherwise considered a rural disease, could reach urban populations. MATERIALS AND METHODS: About 100 ml of voided urine samples from 200 pupils aged 6-13 years [109 (54.5%) males and 91 (45.5%) females], attending an Anglican primary school, Ebute Afuye, and a community primary school, Erepoto, were examined parasitologically for hematuria and S. haematobium ova following informed consent obtained from their parents/guardians. All samples were screened using polymerase chain reaction (PCR) amplification of the schistosome Dra1 gene. Fourteen Bulinus snails collected from the two sites, Ebute Afuye (6) and Erepoto (8), were screened for schistosome infection by the PCR amplification of the schistosome Dra1 gene. PCR-RFLP of the snails' its region was analyzed for species identification and a subregion of the cox1 gene from four infected snails (two from each site) was amplified and sequenced. RESULTS: In the Anglican primary school, Ebute Afuye, and community primary school, Erepoto, 16% and 29% were positive for hematuria, and 16% and 17% had schistosome ova, respectively. PCR analysis showed that 57% and 40% were positive for the infection in Anglican primary school, Ebute Afuye, and community primary school, Erepoto, respectively. PCR screening of the snails confirmed that four from Ebute Afuye and three from Erepoto were infected with schistosomes. PCR-RFLP showed that all the 14 snails were Bulinus truncatus while phylogenetic analysis of the sequenced partial cox1 gene corroborated the PCR-RFLP results. CONCLUSIONS: There was a high prevalence of S. haematobium infection among the participants detected by PCR, which was able to detect infection in cases otherwise shown to be negative by hematuria. We also observed that B. truncatus is one of the snail species responsible for the transmission of urinary schistosomiasis in the Epe community. For national control programs, it is very important that trends in the prevalence and intensity of schistosomiasis in urban cities be monitored.

Effects of salsalate therapy on recovery from vascular injury in female Zucker fatty rats.

OBJECTIVE: Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury. RESEARCH DESIGN AND METHODS: Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied. RESULTS: Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats. CONCLUSIONS: The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.

Intracavernosal administration of sodium nitrite as an erectile pharmacotherapy.

It has been reported that sodium nitrite (NaNO2) can act as a storage form of nitric oxide (NO) that can have beneficial pharmacologic actions. The present study was undertaken to investigate the effects of NaNO2 on erectile function in the rat. The intracavernosal (i.c.) injection of NaNO2 produced dose-related increases in i.c. pressure and decreases in systemic arterial pressure. NaNO2 was 1000-fold less potent than sodium nitroprusside in increasing i.c. pressure. Increases in i.c. pressure in response to NaNO2 were attenuated by the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME). The increases in i.c. pressure in response to NaNO2 were not altered by the xanthine oxidoreductase inhibitor allopurinol. The decreases in systemic arterial pressure in response to i.c. injections of NaNO2 were attenuated by allopurinol and were either unchanged or increased by L-NAME. These data suggest that NaNO2 is converted to vasoactive NO in the corpora cavernosum and systemic vascular bed of the rat by different mechanisms. The present data suggest that the conversion of NaNO2 to vasoactive NO is mediated by NOS in the corpora cavernosum and by xanthine oxidoreductase in the systemic vascular bed of the rat. These data show NaNO2 can serve as a NO donor that increases erectile activity in the rat.

Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide.

BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone conditions and when NO synthase (NOS) was inhibited with N(ω)-nitro-L-arginine methyl ester (L-NAME). Under baseline conditions, intravenous injections of BAY 41-8543 caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and increases in cardiac output. When pulmonary arterial pressure was increased to ∼30 mmHg with an intravenous infusion of U-46619, intravenous injections of BAY 41-8543 produced larger dose-dependent decreases in pulmonary arterial pressure, and the relative decreases in pulmonary and systemic arterial pressure in response to the sGC stimulator were similar. Treatment with L-NAME markedly decreased responses to BAY 41-8543 when pulmonary arterial pressure was increased to similar values (∼30 mmHg) in U-46619-infused and in U-46619-infused plus L-NAME-treated animals. The intravenous injection of a small dose of sodium nitroprusside (SNP) when combined with BAY 41-8543 enhanced pulmonary and systemic vasodilator responses to the sGC stimulator in L-NAME-treated animals. The present results indicate that BAY 41-8543 has similar vasodilator activity in the systemic and pulmonary vascular beds when pulmonary vasoconstrictor tone is increased with U-46619. These results demonstrate that pulmonary and systemic vasodilator responses to BAY 41-8543 are significantly attenuated when NOS is inhibited by L-NAME and show that vasodilator responses to BAY 41-8543 are enhanced when combined with a small dose of SNP in L-NAME-treated animals. The present results are consistent with the concept that pulmonary and systemic vasodilator responses to the sGC stimulator are NO-independent; however, the vasodilator activity of the compound is greatly diminished when endogenous NO production is inhibited with L-NAME. These data show that BAY 41-8543 has similar vasodilator activity in the pulmonary and systemic vascular beds in the rat.