Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

OBJECTIVE: Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. PATIENTS AND METHODS: 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and serum electrolytes were assessed. RESULTS: The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. CONCLUSIONS: Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Effect of active infection on cytochrome P450-mediated metabolism of cyclosporine in renal transplant patients.

BACKGROUND: Infections downregulate cytochrome-P activities and thus may alter drug disposition, especially for drugs with a narrow therapeutic index. Cyclosporine (CyA), still used for the prevention of allograft rejection in renal transplant recipients in Egypt, seems to be affected by these infectious changes, based on random clinical observations. In the present study, the effects of bacterial and fungal infection on CyA metabolism were studied in renal transplant patients and subsequent nephrotoxicity was monitored. METHODS: Twenty renal transplant patients, diagnosed with fungal or bacterial infection, were recruited from the renal transplantation outpatient clinic in Alexandria University Hospitals. No dose adjustment in CyA was performed at least 1 week before the onset of infection. Exclusion criteria were patients with acute or chronic unstable liver disease, elderly patients, and patients on concomitant drugs affecting CyA metabolism. CyA trough levels and serum creatinine (SCR) concentrations were measured by fluorescence polarization immunoassay and enzymatic assay, respectively, pre-infection, during infection and in many cases, post infection. RESULTS: CyA trough levels and SCR concentrations increased significantly during the infection (P < 0.001, P = 0.002) respectively. Of the patients, 87% experienced a concomitant rise in CyA trough level and SCR concentrations. No significant difference between pre-infection and post-infection levels of CyA trough and SCR was found. CONCLUSIONS: CyA trough and SCR levels increased during bacterial and fungal infections and returned to pre-infection levels once the infection was resolved. The data generated stress the importance of monitoring CyA levels during episodes of infection. Our recommendations concerning CyA dose adjustment differ according to severity and duration of infection.

Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase.

This study aimed at comparing the effects of atorvastatin and vitamin E on erectile dysfunction in patients initially irresponsive to sildenafil, with investigation into the underlying possible mechanisms. Sixty patients were randomly divided into three groups: the atorvastatin group received 80 mg daily, the vitamin E group received 400 IU daily and the control group received placebo capsules. Patients were examined both before and after 6 weeks of treatment for biochemical tests; Superoxide dismutase (SOD), glutathione peroxidase (GPO), C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) and for erectile function tests; International index of erectile function (IIEF-5) scores and Rigiscan. Both atorvastatin and vitamin E showed a statistically significant GPO increase (P<0.05) and a statistically significant IL-6 decrease (P<0.05). Only atorvastatin showed a statistically significant increase in NO (15.19%, P<0.05), eNOS (20.58%, P<0.01), IIEF-5 score (53.1%, P<0.001) and Rigiscan rigidity parameters (P<0.01), in addition to a statistically significant decrease in CRP (57.9%, P<0.01). However, SOD showed a statistically significant increase only after vitamin E intake (23.1%, P<0.05). Both atorvatstain and vitamin E had antioxidant and anti-inflammatory activities. Although activating eNOS by atorvastatin was the real difference, and expected to be the main mechanism for NO increase and for improving erectile dysfunction. Atorvastatin, but not vitamin E, is a promising drug for sildenafil nonresponders.