Sustained effects of low dose infliximab in combination with methotrexate in the management of chronic recalcitrant psoriasis

Psoriasis is a chronic inflammatory skin disease whose pathogenesis is modulated by numerous genetic and immunologic factors. During the last decade, our understanding of the pathophysiology of psoriasis has significantly improved, and the disease is now accepted as a T-cell mediated process. This concept has dramatically altered the approach to the treatment of psoriasis. Tumor necrosis factor-alpha (TNF-alpha) is one of the key chemokines in the pathophysiology of psoriasis and its expression is notably increased in psoriatic plaques. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody that binds to both transmembrane and soluble TNF-alpha with high affinity, specificity, and avidity. Presented here is a severe recalcitrant case of psoriasis with sustained benefit from low-dose infliximab in combination with methotrexate.     

Efficacy of verteporfin photodynamic therapy on laser-induced choroidal neovascularization and the ancillary effect on diabetic microvasculopathy

PURPOSE: To demonstrate the efficacy of photodynamic therapy (PDT) in treating choroidal neovascularization (CNV) induced by laser photocoagulation for diabetic macular edema and its ancillary effect on surrounding diabetic microvascular abnormalities. METHODS: A retrospective interventional case series study in a clinical practice setting of four patients with proliferative diabetic retinopathy and clinically significant macular edema who had developed classic CNV in proximity to the area of previous laser photocoagulation. The lesions were treated with verteporfin PDT and followed with serial fluorescein angiography. RESULTS: Compared to the pre-treatment angiogram, an acute reduction in leakage from CNV was noted as soon as 5 days post-PDT and persisted in some areas up to three months post-treatment within the zone of the typical dark choroid pattern. No evidence of any closure of microaneurysms was noted. CONCLUSIONS: Serial fluorescein angiograms demonstrate that PDT appears to have a beneficial effect on CNV induced by laser photocoagulation for diabetic macular edema without any tangible beneficial effect on diabetic microvasculopathy. PDT had no effect on existing microaneurysms.     

Prognostic value of arterial blood gas disturbances for in-hospital mortality in pediatric patients with severe traumatic brain injury

Background

The aim of this study was to evaluate the changes of arterial blood gas as a secondary insult in children and young adults suffering from severe traumatic brain injury, and to assess the correlation, if any, with their in-hospital mortality.

Method

In this cross-sectional study, the medical data of all children and adolescents with severe head trauma admitted to the Rasht Poursina Hospital were reviewed between April 2006 and September 2011. Data including age, gender, GCS upon admission, arrival and daily ABG values for the first 3 days, results of brain CT scan, as well as in-hospital mortality rate were collected. A logistic regression model was used to determine the association between acid–base disturbance and in-hospital mortality after adjustment for potential confounding factors.

Result

Of the 108 patients, 75 % were male and 25 % were female; and 31.5 % of them died in the hospital. Univariate analysis showed a significantly higher risk of mortality in patients who developed mixed metabolic acidosis plus respiratory acidosis on their admission day (OR?=?3.94, p?=?0.012). Multiple logistic regression analysis demonstrated that mixed metabolic acidosis plus respiratory acidosis (OR?=?3.81, 95 % CI?=?1.18–12.27, p-value?=?0.025) and GCS (OR?=?0.457, 95 % CI?=?0.31–0.65, p-value?<?0.001) were two significant predictors of mortality, regardless of other confounding variables.

Conclusion

The results of present study show that, in pediatric patients with severe head injuries, initial mixed metabolic acidosis plus respiratory acidosis and GCS are significant predictors of mortality, but other factors after adjustment for potential confounding factors had no prognostic effect.     

Immunomodulatory oligonucleotides inhibit neutrophil migration by decreasing the surface expression of interleukin-8 and leukotriene B4 receptors

Neutrophils play important roles in many inflammatory diseases. The migration of neutrophils to the inflammatory site is tightly regulated by specific chemokines, of which interleukin-8 (IL-8) and leukotriene B₄ (LTB₄) constitute key mediators by binding to the surface receptors CXCR1/2 and BLT1, respectively. Oligonucleotides (ODN) containing CpG motifs mediate potent immunomodulatory effects through binding to Toll-like receptor 9. So far, knowledge on how ODN can affect neutrophil migration during inflammation is lacking. This study demonstrates that several novel CpG ODN significantly down-regulate the surface expression of CXCR1/2 and BLT1. In addition, the ODN significantly blocked IL-8-induced and LTB₄-induced neutrophil migration in vitro, as well as leucocyte migration in vivo demonstrated in mice by intravital microscopy and in a model of airway inflammation. The down-regulation of CXCR1 is rapid, occurring 15 min after ODN stimulation, and can be mediated through an endosomally independent mechanism. Inhibition of the IL-8 and LTB₄ pathways may provide new opportunities of therapeutic intervention using ODN to reduce neutrophil infiltration during inflammation.     

Alteration in CD8+ T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects.     

Synergistic neuroprotective effects of hyperbaric oxygen and methylprednisolone following contusive spinal cord injury in rat

ObjectiveRecent studies revealed the neuroprotective effects of hyperbaric oxygen (HBO) on spinal cord injury (SCI). Meanwhile, the use of methylprednisolone (MP) is one of the current protocols with limited effects in SCI patients. Accordingly, the aim of the present study was to investigate the effect of combined HBO and MP treatment on SCI.DesignThe present study was conducted on five groups of rats each as follows: Sham group (underwent laminectomy alone at T9 level vertebra); SCI group (underwent moderate contusive SCI); MP group (underwent SCI and received MP); HBO group (underwent SCI and received HBO); HBO + MP group (underwent SCI and simultaneously received MP and HBO). Blood serum and Spinal cord tissue samples were taken 48 h after SCI for analysis of serum ferric reducing antioxidant power (FRAP) and tissue malodialdehyde (MDA) levels as well as immunohistochemistry of caspase-3 and tumor necrosis factor-alpha (TNF-α). Neurological function was evaluated by the Basso–Beattie–Bresnehan (BBB) locomotion scores until the end of experiments. Additionally, histopathology was assessed at the end of the study.SettingMazandaran University of Medical Sciences, Sari, Iran.ResultsCombination therapy with HBO and MP in the HBO + MP group significantly decreased MDA as well as increased FRAP levels compared to other treatment groups. Meanwhile, attenuated TNF-α and Caspase-3 expression could be significantly detected in the HBO + MP group. At the end of treatment, the neurological outcome was significantly improved and the extent of injured spinal tissue was also significantly reduced in the HBO + MP compared to other treatment groups.ConclusionThe results suggest that combined therapy with MP and HBO has synergistic effects on SCI treatment.