Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5-79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7-50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9-18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0-0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06-1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06-8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

The effects of a multistrain potential probiotic (Protexin®), acids, and a bacterin from multidrug-resistant E. coli O26, O78, S. Enteritidis (1,9,12 g.m1,7), and S. Typhimurium (1,4,5,12.i.1,2) on the immune response, haematological parameters, cytokines, and growth parameters of broiler chickens challenged with bacterin live serotypes were investigated. Two experiments were designed using 300 one-day-old chicks (Arbor Acres) randomly assigned to 15 groups. The first experiment comprised 9 groups, including positive and negative control groups and other groups received Protexin®, acids, and the bacterin (0.2 ml/SC), either alone or in combination, on the 1st day. The second experiment contained 6 groups, including positive and negative control groups and other groups received a combination of Protexin®, acids, and the bacterin (0.5 ml/SC) on the 8th day. All the groups except the negative control groups were challenged on the 8th and 16th days in both experiments, respectively, with mixed live bacterin serotypes. The groups that received Protexin®, acids, and the bacterin either alone or in combination revealed significant improvements in the immune response to the bacterin (p ≤ 0.05). The groups in the 1st experiment and most the 2nd experiment groups showed a reduced mortality rate and decreased levels IFN-γ, IL-4, and IL-12 cytokines (p ≤ 0.05). Moreover, these groups demonstrated increases in haematological parameters and reduced rates of infection-caused anaemia. These groups showed significant increases in growth performance parameters, such as body weight, weight gain, and the feed conversion ratio (FCR) (p ≤ 0.05). There was a beneficial effect on 1-day-old chickens produced by combining Protexin®, acids, and the bacterin (0.2 ml/SC).

BACKGROUND: Patients with septic shock commonly require endotracheal intubation under general anaesthesia in the operating theatre, the emergency department, and the intensive care unit. Hypotension is a serious complication after induction of general anaesthesia, especially in patients with circulatory failure. No randomised controlled trials had previously investigated protocols for induction of anaesthesia in septic shock patients. The aim of the current work is to compare two protocols, lidocaine-ketamine combination versus ketamine full-dose for rapid-sequence endotracheal intubation in patients with septic shock.

METHODS: Forty-four adult patients, with septic shock, scheduled for emergency surgical intervention were enrolled in this randomised, double-blinded, controlled study. Patients were randomised to receive either 1 mg/kg ketamine (ketamine group, n = 22) or 0.5 mg/kg ketamine plus 1 mg/kg lidocaine (ketamine-lidocaine group, n = 22) for induction of anaesthesia in addition to 0.05 mg/kg midazolam (in both groups). Our primary outcome was the mean arterial pressure (MAP). Other outcomes included frequency of post-induction hypotension, heart rate, and cardiac output.

RESULTS: Forty-three patients were available for final analysis. The average MAP reading in the first 5 min post-induction was higher in ketamine-lidocaine group than in the ketamine group {82.8 ± 5.6 mmHg and 73 ± 10.2 mmHg, P < 0.001}. Furthermore, the incidence of post-intubation hypotension was lower in the ketamine-lidocaine group than in the ketamine group {1 patient (5%) versus 17 patients (77%), P < 0.001}. The ketamine-lidocaine group showed higher MAP in almost all the readings after induction compared to ketamine group. Other haemodynamic variables including cardiac output and heart rate were comparable between both study groups.

CONCLUSION: Lidocaine-ketamine combination showed less incidence of hypotension compared to ketamine full-dose when used for rapid-sequence endotracheal intubation in patients with septic shock. REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT03844984?cond=NCT03844984&amp;rank=1.

BACKGROUND: Patients with septic shock commonly require endotracheal intubation under general anaesthesia in the operating theatre, the emergency department, and the intensive care unit. Hypotension is a serious complication after induction of general anaesthesia, especially in patients with circulatory failure. No randomised controlled trials had previously investigated protocols for induction of anaesthesia in septic shock patients. The aim of the current work is to compare two protocols, lidocaine-ketamine combination versus ketamine full-dose for rapid-sequence endotracheal intubation in patients with septic shock.

METHODS: Forty-four adult patients, with septic shock, scheduled for emergency surgical intervention were enrolled in this randomised, double-blinded, controlled study. Patients were randomised to receive either 1 mg/kg ketamine (ketamine group, n = 22) or 0.5 mg/kg ketamine plus 1 mg/kg lidocaine (ketamine-lidocaine group, n = 22) for induction of anaesthesia in addition to 0.05 mg/kg midazolam (in both groups). Our primary outcome was the mean arterial pressure (MAP). Other outcomes included frequency of post-induction hypotension, heart rate, and cardiac output.

RESULTS: Forty-three patients were available for final analysis. The average MAP reading in the first 5 min post-induction was higher in ketamine-lidocaine group than in the ketamine group {82.8 ± 5.6 mmHg and 73 ± 10.2 mmHg, P < 0.001}. Furthermore, the incidence of post-intubation hypotension was lower in the ketamine-lidocaine group than in the ketamine group {1 patient (5%) versus 17 patients (77%), P < 0.001}. The ketamine-lidocaine group showed higher MAP in almost all the readings after induction compared to ketamine group. Other haemodynamic variables including cardiac output and heart rate were comparable between both study groups.

CONCLUSION: Lidocaine-ketamine combination showed less incidence of hypotension compared to ketamine full-dose when used for rapid-sequence endotracheal intubation in patients with septic shock. REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT03844984?cond=NCT03844984&amp;rank=1.

Nephropathic cystinosis is a rare disease caused by mutations of the CTNS gene that encodes for cystinosin, a lysosomal cystine/H+ symporter. The disease is characterized by early-onset chronic kidney failure and progressive development of extra-renal complications related to cystine accumulation in all tissues. At the cellular level, several alterations have been demonstrated, including enhanced apoptosis, altered autophagy, defective intracellular trafficking, and cell oxidation, among others. Current therapy with cysteamine only partially reverts some of these changes, highlighting the need to develop additional treatments. Among compounds that were identified in a previous drug-repositioning study, disulfiram (DSF) was selected for in vivo studies. The cystine depleting and anti-apoptotic properties of DSF were confirmed by secondary in vitro assays and after treating mice with 200 mg/kg/day of DSF for 3 months. However, at this dosage, growth impairment was observed. Long-term treatment with a lower dose (100 mg/kg/day) did not inhibit growth, but failed to reduce cystine accumulation, caused premature death, and did not prevent the development of renal lesions. In addition, DSF also caused adverse effects in cystinotic zebrafish larvae. DSF toxicity was significantly more pronounced in mice and zebrafish compared to wild-type animals, suggesting higher cell toxicity of DSF in cystinotic cells.

The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg-1) and esomeprazole (20 mg per kg b.wt) were orally administered for 3 weeks to rats before the induction of gastric injury. Compared with the IND group, BITC could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. BITC significantly preserved the antioxidants (glutathione GSH, superoxide dismutase SOD), nitric oxide (NO), and prostaglandin E2 (PGE2) contents, while decreasing the gastric mucosal malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and myeloperoxidase (MPO) contents. Moreover, BITC remarkably upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NAD(P)H : quinone oxidoreductase (NQO1). In addition, BITC activates the expression of heat shock protein 70 (HSP-70) and downregulated the expression of nuclear factor-κB (NF-κB) and caspase-3 to promote gastric mucosal cell survival. To the best of our knowledge, this study is the first published report to implicate the suppression of inflammation, oxidative stress, and Nrf2 signaling pathway as a potential mechanism for the gastroprotective activity of BITC.