IntroductionCannabinoid hyperemesis syndrome (CHS), is characterized by recurrent episodes of severe nausea and intractable vomiting, preceded by chronic use of cannabis. A pathognomonic characteristic is compulsive bathing in hot water. The resolution of the problem occurs when cannabis use is stopped. However, patients are often reluctant to discontinue cannabis. Treatment with anti-emetic medication is ineffective. Case series suggested haloperidol as a potential treatment. Other antipsychotics as olanzapine has been used as anti-emetic treatment in chemotherapy.ObjectivesTo describe three cases of patients with CHS whom showed a successful response to olanzapine, even when, haloperidol had failed.AimsTo present an alternative treatment for CHS which can offer benefits over haloperidol.MethodsWe present three cases of patients who suffered from CHS and were admitted to emergency department. All patients were treated with olanzapine after conventional anti-hemetic treatment failure. One patient was also unsuccessfully treated with haloperidol.ResultsAll three patients showed a good response to olanzapine treatment. Different presentations were effective: velotab and intramuscular. Their nausea, vomits and agitation were ameliorated. They could be discharge after maintained remission of symptoms.ConclusionsOlanzapine should be considered as an adequate treatment for CHS. Its suitable receptorial profile, its availability in different routes of administration and its side effects profile could offer some benefits over haloperidol.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Background and Aims Massive intravascular hemolysis is a common condition of several pathologies. It is associated with acute kidney injury (AKI) and progressive impairment of renal function. In this context, free hemoglobin (Hb) can exert harmful effects by accumulating in the kidney, where induces oxidative stress and it becomes cytotoxic. NADPH oxidase 4 (Nox4) is the principal source of reactive oxygen species (ROS) in the kidney. Nox4 is mostly expressed in proximal tubular cells with lower levels in glomerulus. The role of Nox4 in renal damage is not clear, with studies reporting beneficial or deleterious actions depending of the environmental conditions. For that reason we aimed to investigate the role of Nox4 in massive intravascular hemolysis-associated AKI. Method To study the role of Nox4 in AKI caused by massive intravascular hemolysis, we performed an experimental model of intravascular hemolysis by intraperitoneal injection of phenylhydrazine (200 mg/kg) in wild type (Nox4+/+) and Nox4 knockout mice (Nox4-/-). Mice were sacrificed 24 and 72 hours after intravascular hemolysis induction. We collected serum, urine and tissues sample. We analyzed renal function, oxidative stress, cell death and inflammation in these samples. In other experiments, wild type mice were treated with GKT137831 (10mg/kg/day), a potent Nox4 and Nox1 inhibitor, and mice were sacrificed 72h after induction of hemolysis. We also performed in vitro experiments in murine tubular epithelial cells (MCT) and murine podocytes cells to investigate the regulation of Nox4 in Hb-stimulated cells treated or not with GKT137831. Results Induction of intravascular hemolysis in Nox4+/+ mice increased creatinine and BUN levels and enhanced the expression of tubular injury markers, such as NGAL. These pathological effects were reduced in Nox4 knockout mice. Then, we analyzed oxidative stress in our experimental model thought determination of HO-1, ferritin, GSH and lipid peroxidation levels. All of these oxidative markers were reduced in Nox4-/- mice with intravascular hemolysis as compared with Nox4+/+ mice. We also observed that inflammatory markers such as IL-6, cell death and podocytes injury markers were reduced in Nox4-/- mice than in wild type mice, specially 72 hours after phenylhydrazine injection. In line with these results, GKT137831 administration ameliorated intravascular hemolysis-associated renal function impairment. Moreover, oxidative stress, tubular injury markers and podocyte injury were reduced in hemolytic mice treated with GKT137831. GKT137831 also reduced Hb- and heme-mediated oxidative stress in MCT and podocytes. Conclusion Our results show the important role of Nox4 in renal injury associated to massive intravascular hemolysis. Moreover, the inhibition of Nox4 may be a potential therapeutic target to prevent renal damage associated to Hb accumulation. These findings provide new insights into novel aspects of Hb-toxicity and may have important pathogenic and therapeutic implications for intravascular hemolysis related diseases

IntroductionHyponatraemia occurs in 4% of schizophrenic patients. Dilutional hyponatraemia, due to inappropriate retention of water and excretion of sodium, occurs with different psychotropic medications and could lead to hippocampal dysfunction. This complication is usually asymptomatic but can cause severe problems, as lethargy and confusion, difficult to diagnose in mentally ill patients.ObjectivesTo describe a case of a patient with psychotropic poli-therapy, admitted three times due to hyponatremia and the pharmacological changes that improved his condition.AimsTo broadcast the intermittent hyponatraemia and polydipsia (PIP), a not rare condition, suffered by treated schizophrenic patients and discuss its physiopathology and treatment thorough a case report.MethodsA 56-year schizophrenic male was admitted for presenting disorganized behavior, agitation, auditory hallucinations, disorientation, ataxia, vomits and urinary retention. He was on clomipramine, haloperidol and clotiapine (recently added), quetiapine, fluphenazine and clonazepam. After water restriction his symptoms improved and he was discharged. Twenty-five days later, he was readmitted for presenting the same symptoms and after water restriction, he was discharged. Five days later, he was again admitted and transferred to the psychiatric ward.ResultsHaloperidol, fluphenazine and clomipramine were replaced by clozapine. These changes lead him to normalize the hypoosmolality and reduce his water-voracity. Endocrinology team did not label this episode of SIADH due to its borderline blood and urine parameters.ConclusionsHyponatremia is frequent in schizophrenic patients and may have severe consequences. Therefore, a prompt recognition and treatment is warranted.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionClozapine (CZP) is the only antipsychotic approved for resistant schizophrenia 1. Due to its side effects, CZP is not the first therapeutic option in a psychotic episode. Its anticholinergic effects often cause constipation, however, diarrhea have also been described in literature.ObjectivesWe describe a patient with two episodes of severe diarrhea after clozapine initiation, which lead to CZP discontinuation.AimsDiscuss about the differential diagnosis of diarrhea in CZP patients and the needing of a further studies for clarify the more appropriate management in CZP induced diarrhea.MethodsWe present a case report of a 46 years man diagnosed with schizoaffective disorder who presented two episodes of severe diarrhea with fever, which forced his transfer to internal medicine and UCI after CZP initiation.ResultsAt the first episode analytical, radiological and histological findings led to Crohn's disease diagnosis, which required budesonide and mesalazine treatment. In the second episode, the digestive team concluded that the episode was due to clozapine toxicity despite the controversial findings (clostridium toxin and Crohn's compatible biopsies)ConclusionsDiarrhea caused by CZP has been controversial in the literature. However due to the severity of digestive episodes and the paucity of alternative treatments further studies for a better understanding of its physiopathology are warranted.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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