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.

Potential of green synthesized titanium dioxide nanoparticles for enhancing seedling emergence, vigor and tolerance indices and DPPH free radical scavenging in two varieties of soybean under salinity stress.

BACKGROUND: Considering titanium dioxide nanoparticles (TiO2 NPs) role in plant growth and especially in plant tolerance against abiotic stress, in the present work, TiO2 NPs were green synthesized using an aqueous solution of Aloe vera leaf extract as a capping agent and titanium tetrachloride as a precursor. These green synthesized TiO2 NPs were characterized using different techniques: UV spectrophotometer, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Results revealed that synthesized TiO2 NPs possess a tetragonal morphology with a size ranging from 10 to 25 nm. Additionally, the present work evaluated the effects of three concentrations of TiO2 NPs (0, 30 and 50 ppm) and six NaCl concentrations (0, 25, 50, 100, 150 and 200 mM) and their interactions with respect to germination parameters, vigor indices, oxidative stress and DPPH free radical scavenging of two varieties of soybean (Glycine max L. var. 22 and 35). RESULTS: Results demonstrated that all germination traits and vigor indices were negatively affected under all salinity levels. Also, the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were significantly increased by increasing the NaCl concentrations in two soybean varieties. Most interestingly, TiO2 NPs (30 ppm) mediated positive effects on germination parameters, reducing H2O2 and MDA contents by enhancing antioxidant (decreasing IC50) whereas 50 ppm showed an intermediate response under both control and saline soil conditions. CONCLUSION: Our findings demonstrate the growth enhancement effects of TiO2 NPs application as well as its ameliorative potential in dealing with salinity.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

BACKGROUND: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. OBJECTIVES: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. METHODS: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. CONCLUSIONS: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

Long-term continuation with secukinumab in psoriasis: association with patient profile and initial psoriasis clearance.

BACKGROUND: There are limited data regarding the long-term continuation with biological therapy for patients with psoriasis. In particular, the reasons for secukinumab discontinuation have not been thoroughly investigated. AIM: To better ascertain the real-life continuation of secukinumab in psoriasis, we conducted a retrospective study to evaluate the incidence, causes and factors of secukinumab discontinuation in patients with psoriasis. METHODS: All patients treated with secukinumab for psoriasis in the Department of Dermatology (Toulouse University and Larrey Hospital, Toulouse, France), between September 2011 and June 2017, were enrolled in the study. RESULTS: Of the 91 patients in the study, 22 (24.2%) discontinued secukinumab. In 14 (15%) patients, the discontinuation was due to loss of efficacy. Two patients stopped treatment because they planned a pregnancy and five patients stopped because of adverse events. A longer disease duration (P = 0.01) and presence of palmoplantar psoriasis (P = 0.01) seem to be predictive factors for treatment failure. Patients reaching 90 or 100% improvement in Psoriasis Area and Severity Index (PASI90 and PASI100, respectively) at weeks 12-16 had a lower risk of long-term treatment discontinuation compared with patients who had less complete clearance (P = 0.04). CONCLUSION: Long-term persistence of secukinumab appears to be good, as only 24.2% (n = 22) of the patients in this study discontinued secukinumab over the follow-up period. Loss of efficacy prompted discontinuation in about 14% of patients by the 2-year follow-up. Persistence appears to be lower in patients with palmoplantar psoriasis and in patients previously exposed to many systemic treatments. Optimal therapeutic response at 12-16 weeks as defined by reaching PASI90-100 seems to be predictive of long-term treatment persistence.

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.

Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma.

Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK(+)ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK(+)ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2(active) cells, but not Sox2(inactive) cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK(+)ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells.

E. coli transport in soil columns: implications for reuse of treated wastewater in irrigation.

Reuse of treated wastewater in irrigation is gaining recognition as a vital element in the water resources management plan of developing countries, especially those situated in arid and semi-arid regions. An understanding of the transport of residual pollutants from treated wastewater, such as bacteria, in soil as a result of irrigation is critical to assessing health risks and the possible contamination of limited groundwater resources. In this work, retention of E. coli is evaluated for a soil that is irrigated by treated wastewater for growth of non-food crops near Egypt's Red Sea coast. In particular, the effects of soil organic fraction (SOF) and hydraulic loading rate (HLR) were investigated in laboratory soil columns. The matrix of experiments included three HLRs and three SOFs. The retention of bacteria by adsorption was observed at HLRs of 5 and 13 cm/h, with the magnitude of the adsorption increasing proportionally to the SOF. The impact of SOF was greater for the lower HLR. At the lowest HLR investigated (5 cm/h), filtration was also observed for the two higher SOFs (0.674 and 2.04 per cent). At a high HLR (66 cm/h) simulating flood irrigation, retention of bacteria was minimal regardless of the SOF. Since the bacterial solution is applied to a dry soil column to simulate field conditions, E. coli breakthrough after two pore volumes of throughput (vs. one) provided a meaningful comparison of bacterial retention as a function of HLR and SOF.

Pond treatment and effluent reuse of sewage from an oil production site in an arid coastal environment.

A pond system consisting of two lines each of an anaerobic followed by facultative and maturation ponds is used to treat site sewage from oil and gas production operations in an arid coastal environment. The performance of the pond system was evaluated together with the suitability of treated effluent for reuse in local irrigation. Effluent from the pond system by-and-large satisfies criteria for irrigation of non-food crop plants with respect to chemical parameters. The primary problem is coliform bacteria levels which are an order of magnitude higher than preferred values. First-order decay rate constants for each pond were calculated from a mass balance model that assumes complete mixing and incorporates the considerable evaporation that occurs in this setting. While the anaerobic ponds of both lines exhibit suitable performance, rate calculations indicate that the facultative and maturation ponds of the East Line are performing better than the West. A tracer study of the facultative and maturation ponds indicates that some short-circuiting is occurring in the West Line. A field experiment of coliform transport in irrigated soil gives indications of short- and long-term risks associated with reuse of the effluent.

Comparison of the effects of dietary selenium, zinc, and selenium and zinc supplementation on growth and immune response between chick groups that were inoculated with Salmonella and aflatoxin or Salmonella.

The effects of four diets (basal diet, Se, Zn, and Se- and Zn-enriched diets) fed to chicks that were administered one of three treatments [Salmonella and aflatoxin inoculation (T1), Salmonella inoculation (T2), or uninoculated (T3)] were investigated for growth and immune responses. We found a significant improvement in growth performance represented by relative body gain (RBG) and feed efficiency (FE), for the Zn- and Se + Zn-enriched diets fed to the T1 and T2 groups. The antibody immune response was significantly improved for the Se enrichment diet in the T1 and T2 groups. The weight of the bursa and thymus, which relate to the level of the immune response, showed significant decreases, whereas the spleen had a significantly increased relative weight (RW) in the T1 group. The variable dietary trace elements supplement increased the thymic RW in the T2 group.

Effect of dual infections of Escherichia coli and pure caecal Eimeria sp. in broiler chickens.

The interactive effect of Escherichia coli and pure caecal Eimeria spp. in broiler chickens was studied. Single and dual orally inoculations were assessed in six groups of 20 chicks each. Neither mortalities nor clinical signs were recorded on inoculated groups or control. There was a significant decrease in body weights in groups infected, either with E. coli or caecal Eimeria spp. or with both pathogens. The total oocyst output and caecal lesion score were high and severe in chicks infected with caecal Eimeria sp. alone or with E. coli prior to caecal Eimeria infection. Low oocyst output and moderate caecal lesion score were noticed in chicks inoculated with E. coli prior to or together with caecal Eimeria infection. The results suggested a synergistic action between E. coli and caecal Eimeria sp. in producing gross lesions. The electrophoretic distribution of serum proteins decreased in all chicks compared with control. The changes in serum protein fractions differed in inoculated groups and all protein components decreased quantitatively compared with controls. It was also shown that E. coli did not always invade the blood stream.

Munchausen' syndrome and trihexyphenidyl dependence.

The authors describe a woman with Munchausen's syndrome who, during the course of illness, developed dependence on Trihexyphenidyl which besides being partially treated was used in establishing the stable linkage with a hospital and was also successfully utilized in the management of Munchausen's syndrome.

Interaction of naturally occurring aflatoxins in poultry feed and immunization against fowl cholera.

A total of 1,175 poultry feed samples originating from different farms were analyzed for aflatoxin. Poor growth rate and reduced egg production were the main complaints. The rate of contamination with aflatoxin ranged from 10 to 54% of all samples. Of samples examined 30.7% proved positive for aflatoxin with a concentration ranging from 1 to 2,000 ppb. Outbreaks of fowl cholera were diagnosed on two farms where aflatoxin was detected in the rations used. The impact of aflatoxin in the feed on the efficacy of immunization against fowl cholera was monitored by a hemagglutination test and the titers of the involved farms were compared with experimental groups fed on aflatoxin-free rations and vaccinated with the same polyvalent fowl cholera bacterin. The antibody titers of the experimental groups were 4 to 15 times higher than those of the involved farms.

Heated fats. Part 3. Biological effect and effect of heating and tempering oils on fatty acid composition of liver, heart and serum lipids of rats.

The study deals with the biological effect caused by changes in fats during heating. The study includes feeding experiments and extraction of serum, liver, and heart from the animals tested. The biological study reveals that animals fed heated oil showed retardation of growth, poor efficiencies, rough, greasy mottled coats, and shortened life span.