Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats

Background: A number of neuroimaging studies on human addicts have revealed that abuse of Methamphetamine (METH) can induce neurodegenerative changes in various brain regions like the cerebral cortex and cerebellum. Although the underlying mechanisms of METH-induced neurotoxicity have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be clarified. Previous studies implicated that cannabinoid type 1 receptors (CB1Rs) exert neuroprotective effects on several models of cerebral toxicity, but their role in METH-induced neurotoxicity has been rarely investigated. Moreover, the cerebellum was considered as a potential target to evaluate the effects of cannabinoids on locomotion activity as the CB1Rs are most widely distributed in the molecular layer of cerebellum. Therefore, the present study was carried out to evaluate whether neurodegeneration induced in the cerebellum tissue implicated in locomotion deficit induced by METH.Methods: In the current study, open field test was used to examine locomotor activity. Using hematoxylin and eosin (H&E) staining, morphology of the cerebellar vermis was investigated after repeated exposure to METH. Then, the effects of CB1Rs antagonist [SR17141A, 10 mg/kg, intraperitoneally (IP)] and CB1Rs agonist [WIN55, 212-2 (WIN), 3 mg/kg] against METH-induced neurodegeneration and locomotor deficit were assessed.Findings: The results of the present study demonstrated that repeated exposure to METH increased cerebellar degeneration level as compared to the saline and dimethyl sulfoxide (DMSO) groups. In addition, METH-treated rats showed hyperactivity as compared to the saline and DMSO groups. Pretreatment with WIN significantly attenuated neurodegeneration and hyperactivity induced by METH.Conclusion: The findings of this study provided evidence that CB1Rs may serve as a therapeutic strategy for attenuation of METH-induced locomotor deficits

A Study of Matrix Metalloproteinase 9 and CD31 Expression through Immunohistochemistry in Invasive Breast Cancer

Abstract: Background & Aims: This study was performed to investigate possible relationships between the manifestation of stromal cells (fibroblasts and/or myofibroblasts) by focusing on expression of their matrix metalloproteinase 9 (MMP9) and possible angiogenesis based on CD31 and CD34 antigen expression during the various steps of hyperplastic changes to precancerous state and invasive breast cancer. Methods: Our study included 50 females with invasive ductal carcinoma. Samples were obtained by mastectomy or biopsy and were immunohistochemically stained for the MMP9, CD31, and CD34 antibody. microvessel count (MVC) was also carried out on samples. Statistical analysis of the data was performed using ANOVA and Student's t-test (P < 0.05). Findings were compared with our "Breast Cancer Data Bank" for reevaluation of their clinical staging. Results: Positive significant correlations were observed between expression of MMP9 and invasive ductal carcinoma in situ (DCIS) and fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN) areas (P=0.001). MMP9 expression in invasive areas was more strongly positive than precancerous areas. Statistically significant correlations were observed between MMP9 expression and CD31 in grade II in invasive areas. MVC was evaluated by CD31 antibody. It was found to be inversely related to increased MVC from invasive areas, DCIS, DIN, and normal areas (P<0.001). No significant difference was observed in MVC based on age, tumor size or steroid receptors in stroma of an invasive cancer, DCIS, and FCD ± DIN. Conclusion: MMP9 expression in invasive areas was more strongly positive than precancerous areas, and negative in normal areas. Angiogenesis can be observed before any significant changes in preinvasive breast lesions. The elevated content of microvessel count of the tumor may be an indicator for worse prognostic factor. The progression from epithelial hyperplasia toward DCIS, and then, invasive carcinoma seems too complex to be assumed a linear progression. Keywords: Invasive breast carcinoma, Ductal carcinoma in situ (DCIS), Ductal intraepithelial neoplasia (DIN), Matrix metalloproteinase 9 (MMP9), CD3

Off-Pump Coronary Bypass Grafting Causing Stunned Myocardium

The term “stunned myocardium” refers to abnormalities in the myocardial function following reperfusion and is common in on-pump coronary artery bypass grafting (CABG) and is exceedingly rare in off- pump CABG. A 53-year-old man presented with unstable angina due to the severe stenosis of the left anterior descending coronary artery (LAD) and the obtuse marginal. Laboratory findings and Chest X-ray revealed nothing abnormal. The intraoperative course was uneventful. The patient left the operating room without any inotropic support. Six hours later, however, he developed low cardiac output .At exploration, cardiac tamponade was excluded and flowmetry showed that the graft had adequate function. Cardiac enzymes were normal. High-dose adrenalin and Dobutamine were administrated and an intra-aortic balloon pump was used. After hemodynamic stabilization, the patient left the Intensive Care Unit without an intra-aortic balloon pump and inotropic support. On the fifth postoperative day, coronary angiography showed patent grafts and correct anastomotic sites. On the seventh postoperative day, the akinetic lateral wall of the left ventricle changed to dyskinesia. Finally after hospital discharge on the thirtieth postoperative day, an echocardiogram showed normal left ventricular function without regional wall motion abnormalitie

Adjunctive hemoperfusion with Resin Hemoadsorption (HA) 330 cartridges improves outcomes in patients sustaining multiple Blunt Trauma: a prospective, quasi-experimental study

Abstract Background Multi-organ dysfunction syndrome and multi-organ failure are the leading causes of late death in patients sustaining severe blunt trauma. So far, there is no established protocol to mitigate these sequelae. This study assessed the effect of hemoperfusion using resin-hemoadsorption 330 (HA330) cartridges on mortality and complications such as acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) among such patients. Methods This quasi-experimental study recruited patients ≥ 15 years of age with blunt trauma, injury severity score (ISS) ≥ 15, or initial clinical presentation consistent with SIRS. They were divided into two groups: the Control group received only conventional acute care, while the case group received adjunctive hemoperfusion. P-values less than 0.05 were statistically significant. Results Twenty-five patients were included (Control and Case groups: 13 and 12 patients). The presenting vital signs, demographic and injury-related features (except for thoracic injury severity) were similar (p > 0.05). The Case group experienced significantly more severe thoracic injuries than the Control group (Thoracic AIS, median [IQR]: 3 [2–4] vs. 2 [0–2], p = 0.01). Eleven and twelve patients in the Case group had ARDS and SIRS before the hemoperfusion, respectively, and these complications were decreased considerably after hemoperfusion. Meanwhile, the frequency of ARDS and SIRS did not decrease in the Control group. Hemoperfusion significantly reduced the mortality rate in the Case group compared to the Control group (three vs. nine patients, p = 0.027). Conclusions Adjunctive Hemoperfusion using an HA330 cartridge decreases morbidity and improves outcomes in patients suffering from severe blunt trauma

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely