Effect of minocycline on cerebral ischemia- reperfusion injury

Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein expression.     

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth,which is in large part mediated by the Nogo-66 receptor,affects neural regeneration following bone marrow mesenchymal stem cell transplantation.The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers.The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells,which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats.Simultaneously,rats treated with scaffold only were taken as the control group.Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation,rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only,and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased.At 8 weeks after transplantation,horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers,as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury.These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.     

Guideline-Based Antibiotics and Mortality in Healthcare-Associated Pneumonia

Background

Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP.

Objective

To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP.

Design

Multi-center retrospective study.

Participants

Thirteen hundred and eleven admissions for HCAP in six Veterans Affairs Medical Centers.

Interventions

Each admission was classified as receiving GST, anti-MRSA or anti-pseudomonal components of GST, or other non-HCAP therapy initiated within 48 hours of hospitalization. Association between 30-day mortality and GST was estimated with a logistic regression model that included GST, propensity to receive GST, probability of recovering an organism from culture resistant to antibiotics traditionally used to treat community-acquired pneumonia (CAP-resistance), and a GST by CAP-resistance probability interaction.

Main Measures

Odds ratios and 95% confidence intervals [OR (95% CI)] of 30-day mortality for patients treated with GST and predicted probability of recovering a CAP-resistant organism, and ratio of odds ratios [ROR (95% CI)] for treatment by CAP-resistance probability interaction.

Key Results

Receipt of GST was associated with increased odds of 30-day mortality [OR?=?2.11 (1.11, 4.04), P?=?0.02)] as was the predicted probability of recovering a CAP-resistant organism [OR?=?1.67 (1.26, 2.20), P?P?=?0.05].

Conclusions

For HCAP patients with high probability of CAP-resistant organisms, GST was associated with lower mortality. Consideration of the magnitude of patient-specific risk for CAP-resistant organisms should be considered when selecting HCAP therapy.     

The short- and medium-term results of transcatheter closure of atrial septal defect with severe pulmonary arterial hypertension

We investigated the short-term and medium-term results in patients with pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) undergoing transcatheter closure. Fifteen patients with severe PAH associated with ASD who underwent successful occluder implantation from 2007 to 2010 were included. Clinical, echocardiographic, and hemodynamic data were reviewed. Severe PAH was defined as pulmonary arterial systolic pressure measured by catheterization was ≥60 mmHg and pulmonary vascular resistance (PVR) ≥6 Wood Units (WU). Compared with baseline, the 6-minwalking distance significantly increased by 29.7 ± 26.3 m (P < 0.001) at 3 months (short-term) and 65.4 ± 63.6 m (P < 0.001) at 23.4 ± 9.7 months (medium-term), World Health Organization function class considerably improved after postclosure short-term and medium-term. Repeat cardiac catheterization (n = 7) showed that mean pulmonary arterial pressure decreased from 51.6 ± 9.4 mmHg at baseline to 21.0 ± 3.8 mmHg (P < 0.001) at follow-up of 12 months. The PVR decreased by 5.6 ± 1.1 WU (P < 0.001). Through carefully selected patients with severe PAH associated with ASD, transcatheter closure can be safely performed with a promising short-term and medium-term outcome. Trial occlusion is an effective way for deciding the reversibility of severe PAH in ASD patients. The role of aerosolized iloprost for pulmonary vasoreactivity testing in patients with severe PAH secondary to ASD requires further investigation.     

Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on clinical outcomes of peptic ulcer bleeding

Background and Aim: The most effective schedule of proton pump inhibitor (PPI) administration and the optimal timing of endoscopy in acute peptic ulcer bleeding remain uncertain. The aim of this study was to determine the most efficient PPI regimen and optimal timing of endoscopy. Methods: Consecutive patients with suspected bleeding peptic ulcers were enrolled and randomized to receive either a standard regimen or a high‐dose intensive intravenous regimen. Only patients with bleeding peptic ulcers diagnosed at initial endoscopy continued the study. High‐risk patients received endoscopic hemostasis. The primary outcome measure of recurrent bleeding was compared between the two dosage regimens and between early and late endoscopy. Secondary outcome measures compared included need for endoscopic treatment, blood transfusion, hospital stay, surgery and mortality. Results: A total of 875 patients completed the study. Recurrent bleeding occurred in 11.0% in the standard regimen group, statistically higher than that in the intensive regimen group (6.4%, P = 0.02). Mean units of blood transfused and duration of hospital stay were also higher in the standard regimen group (P < 0.001 for each compared to intensive regimen group). However, no significant differences were noted between the two groups in the need for endoscopic hemostasis, need for surgery, and mortality. Recurrence of bleeding was similar between the early and late endoscopy groups. Units of blood transfused and length of hospital stay were both significantly reduced with early endoscopy. Conclusion: High‐dose PPI infusion is more efficacious in reducing rebleeding rate, blood transfusion requirements and hospital stay. Early endoscopy is safe and more effective than late endoscopy.     

Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus

Exophiala spinifera can induce both phaeohyphomycosis and chromomycosis. To date there have been 18 human infections caused by E. spinifera in the English literature. A case of E. spinifera-induced phaeohyphomycosis in a patient with systemic lupus erythematosus (SLE) is described. Direct microscopic examination of the pus showed branched, septate and chained hyphae and spores. A dark green velvety colony grew on Sabouraud dextrose agar. Slide culture showed branched, septate hyphae and spine-like annellated conidiophores. Histopathological biopsy revealed yellowish brown hyphae and spores. The isolate was identified as E. spinifera by DNA sequence analysis. The strain was unable to liquefy gelatin, grew at 25°C to 39°C, and was sensitive to itraconazole, amphotericin B, and terbinafine. To our knowledge, this is the first case of cutaneous phaeohyphomycosis caused by E. spinifera in SLE patients.     

Germline promoter hypermethylation of tumor suppressor genes in gastric cancer

AIM: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16^INK4a in suspected cases of hereditary gastric cancer (GC).METHODS: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16^INK4a tumor suppressor genes. Genomic DNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfite DNA sequencing for a specific region of the MLH1 promoter. The methylation status of CDH1 or P16^INK4a was assayed using methylation-specific PCR. Clonal bisulfite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions.RESULTS: Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16^INK4a genes was detected.CONCLUSION: Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16^INK4a gene is not a frequent event.     

Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

AIM: To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis.METHODS: Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features.RESULTS: Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001).CONCLUSION: The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.