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Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma N[O.sub.x] concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway. Key words: hepatic encephalopathy, opioids, naltrexone, nitric oxide, cirrhosis, acute, chronic, rats. De recentes etudes laissent entendre que les opioides endogenes et l'oxyde nitrique (NO) joueraient un role dans la physiopathologie de l'encephalopathie hepatique (EH). Dans les presents travaux, nous avons etudie l'interaction entre les antagonistes des recepteurs opioides et le NO dans un modele de cirrhose provoquee par les lipopolysaccharides (LPS) chez le rat. Des rats males ont ete repartis dans des groupes avec intervention chirurgicale factice (<>) ou ligature du canal choledoque (LCC). Nous avons administre aux animaux une solution saline; de la naltrexone (a 10 mg/kg par voie i.p.); du L-NAME (a 3 mg/kg par voie i.p.); ou les deux agents en association. Pour provoquer l'EH, nous avons injecte des LPS (a raison de 1 mg/kg par voie i.p.) une heure apres le dernier traitement medicamenteux. Nous avons pris en note les scores d'EH, les resultats d'examens histopathologiques du foie et les taux de metabolites du NO dans le plasma ainsi que le taux de mortalite. Le degre de deterioration de l'etat de conscience et le taux de mortalite a la suite de l'administration de LPS ont nettement diminue avec l'administration tant aigue que chronique de naltrexone chez les rats cirrhotiques. Par contre, ni l'administration aigue ni l'administration chronique de L-NAME n'a permis de faire varier les scores d'EH chez les rats cirrhotiques. Cependant, bien que le L-NAME ait contre les effets aigus de la naltrexone sur les parametres de l'EH, cela n'a pas ete le cas pour les effets chroniques. Par ailleurs, les traitements aigus et chroniques par la naltrexone ou le L-NAME ont permis de diminuer de facon notable la hausse des taux plasmatiques de N[O.sub.x] dans le groupe LCC. Ces resultats laissent entendre que l'administration aigue comme chronique de naltrexone aurait permis d'attenuer l'EH provoquee par les LPS. Mais, seul le traitement aigu par la naltrexone pourrait agir en passant par la voie de signalisation du NO. [Traduit par la Redaction] Mots-cles: encephalopathie hepatique, opioides, naltrexone, oxyde nitrique, cirrhose, aigu, chronique, rats., Introduction Hepatic encephalopathy (HE) is a neuropsychiatric complication in patients with chronic or acute liver disease, which leads to changes in personality, intellectual function, and neuromuscular coordination (Butterworth 2000; Rodrigo [...]

Accidental or intentional poisoning with Aluminum phosphide (AlP) is associated with severe complications such as metabolic acidosis, cardiac failure, and death. Previous animal experiments demonstrated that fresh-packed RBC is protective in an experimental model of AlP poisoning. The aim of this study was to assess the effect of fresh-packed RBC on survival in patients admitted to a referral hospital due to AlP poisoning in a randomized clinical trial. Eighty-two patients were admitted to Clinical Toxicology Unit at Baharloo Hospital due to acute AlP poisoning after approval by the Iranian Registry of Clinical Trials (registration reference: IRCT20180428039443N1). All patients received standard treatment, and forty-one of them received fresh-packed RBC. There was no significant difference between groups in the underlying characteristics, including vital signs and laboratory investigations. But interestingly, the mortality rate was meaningfully decreased (difference: 31.7%, 95% CI: 0.10-0.52) in patients receiving fresh-packed RBC (10 deaths/31 survived; 24.4% mortality) in comparison to standard treatment patients (23 deaths/18 survived; 56.1% mortality). Furthermore, fresh-packed RBC substantially improved the GCS, systolic/diastolic blood pressure, ST changes, and pH 12- and- 24 hours after admission. This study showed that fresh-packed RBC infusion alongside standard supportive treatment leads to a decrease in mortality rate; also, it provided evidence for a protective role of fresh-packed RBC in the management of patients with acute AlP poisoning. [ABSTRACT FROM AUTHOR]

In this study, the relaxatory effect of DETA-NONOate is compared with that of papaverine on isolated human internal mammary artery. We investigated the inhibitory effects of DETA-NONOate and papaverine on phenylephrine-induced contractile response in internal mammary artery segments. The internal mammary artery segments, taken from methodologically matched patients who underwent coronary artery bypass grafting, were prepared, placed in an organ bath, and contracted with phenylephrine ([10.sup.-9] to [10.sup.-4] mol/L) to investigate their relaxatory response to DETA-NONOate or papaverine. Phenylephrine dose-response contraction was obtained after 1, 2, and 3 h in segments pre-incubated with DETA-NONOate or papaverine for 30 min. The [EC.sub.50] that presented for internal mammary artery segments incubated with DETA- NONOate was 3.523 ± 1.2696 X [10.sup.-7] mol/L, and for papaverine was 3.467 ± 1.2145 X [10.sup.-6] mol/L. In segments pre-incubated with DETA-NONOate, the contractile response to phenylephrine was suppressed in the first 2 h post-incubation, compared with control responsive groups (p < 0.05), but this inhibition was revoked after 3 h post-incubation. We showed that DETANONOate has a more significant relaxative effect by comparison with papaverine; moreover, continuous and long-lasting nitric oxide production by DETA-NONOate might be of great importance for the outcome from coronary artery bypass grafting, when internal mammary artery is used as a conduit. Key words: coronary artery bypass graft, DETA-NONOate, vasodilation, papaverine, IMA. Dans la presente etude, nous comparons l'effet relaxant du DETA-NONOate avec celui de la papaverine sur l'artere mammaire interne isolee de l'humain. Nous avons examine les effets relaxants des deux composes sur la reponse contractile induite par la phenylephrine dans des segments d'arteres mammaires internes. Les segments, preleves chez des patients methodologiquement apparies ayant subi un pontage coronarien, ont ete prepares, places dans un bain d'organe et contractes avec de la phenylephrine ([10.sup.-9] - [10.sup.-4] mol/L) afin d'examiner leur reponse a la relaxation induite par le DETANONOate ou la papaverine. Une contraction dose-reponse a la phenylephrine a ete obtenue apres 1, 2 et 3 heures dans les segments pre-incubes avec le DETA-NONOate ou la papaverine pendant 30 minutes. La [CE.sub.50] a ete de 3,523 ± 1,2696 X [10.sup.-7] mol/L pour les segments incubes avec le DETA-NONOate et de 3,467 ± 1,2145 X [10.sup.-6] mol/L pour ceux incubes avec la papaverine. Dans les segments preincubes avec le DETA-NONOate, la reponse contractile a la phenylephrine a ete supprimee dans les deux premieres heures de post-incubation comparativement a celle des groupes temoins (p < 0,05), mais cette inhibition a ete annulee trois heures apres la fin de l'incubation. Nous avons montre que le DETA-NONOate a un effet relaxant plus significatif que celui de la papaverine; de plus, une production continue et de longue duree de monoxyde d'azote par le DETA-NONOate pourrait etre d'une grande importance pour les resultats des pontages coronariens utilisant l'artere mammaire interne comme greffon. Mots-cles : pontage coronarien, DETA-NONOate, vasodilatation, papaverine, IMA. [Traduit par la Redaction], Introduction Coronary artery bypass graft (CABG) is an important therapy in coronary artery diseases. Bypass grafts are usually made from sections of the internal mammary artery (IMA) and the saphenous [...]

To evaluate the effects of modafinil on neuropathic pain induced by sciatic nerve cuffing in mice, and possible contribution of nitrergic/inflammatory and serotonergic systems. Neuropathic pain was induced by applying a polyethylene cuff around the left sciatic nerve. Seven days later, mice received modafinil (50, 100, and 200 mg/kg; intraperitoneal [i.p.]) and morphine (10 mg/kg, i.p.) as control. Mice also received pretreatments of the nonselective nitric oxide (NO) synthase (NOS) inhibitor L-NAME, the selective neuronal NOS inhibitor 7-nitroindazole, the selective inducible NOS inhibitor aminoguanidine, and the selective serotonin reuptake inhibitor citalopram before modafinil (100 mg/kg). von Frey test was used to evaluate mechanical allodynia. Additionally, sciatic nerves were collected for histopathological analysis. Tissue levels of NO metabolites, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were assessed. Animals whose sciatic nerves were cuffed had a significantly (P<0.001) decreased paw withdrawal threshold (PWT) compared with the sham-operated group. Modafinil (100 mg/kg) and morphine significantly reversed PWT (P<0.001). Pretreatments with L-NAME, 7-nitroindazole, aminoguanidine, and citalopram in different groups markedly reversed analgesic effects of modafinil. Tissue homogenates of Cuffed sciatic nerves showed significantly higher levels of NO metabolites, TNF-α and IL-6 (P<0.001). Modafinil lowered NO metabolites, TNF-α, and IL-6 levels (P<0.001). Histopathology illustrated marked axonal degeneration and shrinkage in the cuffed sciatic nerve, which were improved in the modafinil-treated group. Modafinil exerts analgesic and neuroprotective effects in cuff-induced neuropathic mice via possible involvement of the nitrergic/inflammatory and serotonergic systems. [ABSTRACT FROM AUTHOR]