Blocking Type I Interferon Signaling Rescues Lymphocytes from Oxidative Stress, Exhaustion, and Apoptosis in a Streptozotocin-Induced Mouse Model of Type I Diabetes

Elevated levels of type I interferon (IFN) during type 1 diabetes mellitus (T1D) are associated with a defective immune response. In the present study, we investigated whether blocking type I IFN signaling during streptozotocin- (STZ-) induced T1D in mice improves lymphocyte proliferation and escape from continuous apoptosis. Three groups of mice were examined: diabetic mice, type I IFN signaling-incompetent diabetic mice, and control nondiabetic mice. We first found that diabetes induction was accompanied by an elevation in the plasma levels of reactive oxygen species (ROS), hydroperoxide, malondialdehyde (MDN), and the proinflammatory cytokines IL-1α, IL-1β, IL-6, and CXCL10. Blocking type 1 IFN signaling in diabetic mice significantly decreased the levels of oxidative stress and proinflammatory cytokines. In addition, lymphocytes from diabetic mice exhibited a marked reduction in their proliferative capacity, increased apoptosis, upregulation of the exhaustion marker PD-1, and aberrant phosphorylation of STAT1, STAT2, AKT and IκB-α. Interestingly, following the blocking of type I IFN signaling in diabetic mice, the lymphocytes exhibited restored proliferative capacity, decreased apoptosis, normal expression of PD-1, and normal phosphorylation of STAT1, STAT2, AKT and IκB-α. Our data suggest that elevated levels of type I IFN during T1D trigger lymphocyte exhaustion and a defective lymphocyte-medicated immune response

Modified periacetabular osteotomy technique in the management of acetabular dysplasia

Purpose: Evaluating the results of modified PAO in the management of acetabular dysplasia. Patients and Methods:  This prospective study included 13 cases. All cases were diagnosed with acetabular dysplasia then treated by PAO using our modified technique. In all included patients, the retro-acetabular cut was performed before the ischial cut during PAO surgery. Eight cases were stage IV and five were stage III according to Severin classification. The mean preoperative HHS was 83 points. The mean preoperative acetabular angle of Sharp value was 49 degrees. The mean preoperative LCEA value was 12 degrees. Results: The mean postoperative HHS at the final follow up was 87 points. The mean postoperative acetabular angle of Sharp value was 37 degrees. The mean postoperative LCEA value was 32 degrees. According to HHS score, six cases had excellent results, six had good results, and one case had fair outcome. Lateral femoral cutaneous nerve neuropathy occurred in two patients, and superficial wound infection was encountered in one patient.Conclusion: Performing the retro-acetabular cut before the ischial cut prevented posterior column fracture Interruption in all cases, making PAO safer and easier to perform, and reducing its risk

Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba (M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication. Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis (comet assay) and determination of DNA fragmentation. Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M. alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration. Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy

Development of sensitive molecular markers for detecting the genotoxicity induced by two pyrethroids insecticides, Cypermethrin and permethrin, to the Meditnerranean sole, Solea senegalensis (Kaup 1858)

The effects of two pyrethroid insecticides, cypermethrin and permethrin, on juvenile Senegalese sole, Solea senegalensis, were assessed. For this purpose, LC50 at 24 h and 72 h were determined as 500 μg L-1 and 900 μg L-1, respectively. The specimens were divided into 5 experimental groups exposed to: i) ethanol vehicle in sea water (control), ii) 1/25 of cypermethrin LC50 (20 μg L-1), iii) 1/10 of cypermethrin LC50 (50 μg L-1), iv) 1/25 of permethrin LC50 (36 μg L-1) and v) 1/10 of permethrin LC50 (90 μg L-1) during 10 days. At the end of the experiment, gill and hepatic samples were obtained for studying the expression patterns of different enzyme genes related to toxicity and osmoregulation, namely glyceraldehyde-3-phosphate dehydrogenases1 and 2 (GAPDH-1 and 2), and Na+, K+-ATPase subunits α and β (NKA α and β). Both pyrethroid insecticides enhanced gill GAPDH-1, NKA-αand NKA-β expressions. However, hepatic responses were less prominent. The low dose of cypermethrin decreased GAPDH-2 expressions. Also, the lowest permethrin dose decreased GAPDH-2 expression. These results indicate that pyrethroids induce some degree of oxidative stress in Solea senegalensis specimens led to an osmotic imbalance, activating -mainly at branchial level- different antioxidant and osmoregulatory enzyme genes. © 2014 Ibrahim El-Elaimy et al.This study was partly supported by grants Proyecto de Excelencia PO7-RNM-02843 (Junta de Andalucía, Andalucía Governerate, Spain) to JMM.Peer Reviewe

Increased Levels of Type 1 Interferon in a Type 1 Diabetic Mouse Model Induce the Elimination of B Cells from the Periphery by Apoptosis and Increase their Retention in the Spleen

Background: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. Aims: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. Methods: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. Results: We observed that induction of T1D was accompanied by a marked destruction of β cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. Conclusion: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D