Decreased microglial activation in MS patients treated with glatiramer acetate

Activated microglia are thought to be an important contributor to tissue damage in multiple sclerosis (MS). The level of microglial activation can be measured non-invasively using [(11)C]-R-PK11195, a radiopharmaceutical for positron emission tomography (PET). Prior studies have identified abnormalities in the level of [(11)C]-R-PK11195 uptake in patients with MS, but treatment effects have not been evaluated. Nine previously untreated relapsing-remitting MS patients underwent PET and magnetic resonance imaging of the brain at baseline and after 1 year of treatment with glatiramer acetate. Parametric maps of [(11)C]-R-PK11195 uptake were obtained for baseline and post-treatment PET scans, and the change in [(11)C]-R-PK11195 uptake pre- to post-treatment was evaluated across the whole brain. Region-of-interest analysis was also applied to selected subregions. Whole brain [(11)C]-R-PK11195 binding potential per unit volume decreased 3.17% (95% CI: -0.74, -5.53%) between baseline and 1 year (p = 0.018). A significant decrease was noted in cortical gray matter and cerebral white matter, and a trend towards decreased uptake was seen in the putamen and thalamus. The results are consistent with a reduction in inflammation due to treatment with glatiramer acetate, though a larger controlled study would be required to prove that association. Future research will focus on whether the level of baseline microglial activation predicts future tissue damage in MS and whether [(11)C]-R-PK11195 uptake in cortical gray matter correlates with cortical lesion load.     

不同丁香提取物对戊四唑诱导的小鼠癫痫发作的影响

目的：研究不同丁香提取物对戊四唑引发小鼠癫痫的作用。方法：实验小鼠被随机分为生理盐水对照组、不同剂量（50、100、250及500mg／kg）丁香水提取物组、不同剂量（50、100、250及500mg／kg）丁香乙醇提取物组、不同剂量（50、100、250及500mg／kg）丁香三氯甲烷提取物组。给予戊四唑前60rain为各组小鼠注射药物。记录并比较各组小鼠阵发性强直性抽搐潜伏期（generalizedtonic-clonicseizure,GTCS）、最小阵发性痉挛潜伏期（minimalclonicseizure,MCS）及死亡率。结果：低、中、高三种剂量的丁香水提取物能有效延长MSC和GTCS的潜伏期（P〈0．05）。50、100和250mg／kg的丁香乙醇提取物显著增加了小鼠MCS潜伏时间（P〈0．05）。与盐水治疗组相比,惊厥小鼠模型经50、100、250和500mg／kg丁香的乙醇提取物治疗后,其GTCS的潜伏期显著高于盐水治疗组,但丁香的三氯甲烷提取物对惊厥小鼠的GTCS和MCS潜伏期没有显著的影响。结论：丁香乙醇和水提取物能抑制由戊四唑诱发的小鼠惊厥,但其确切的作用机制和有效的抗惊厥活性物质还有待进一步的研究。     

Structure–cytotoxicity relationship of a novel series of miconazole-like compounds

In the current study, two novel classes of the carboacyclic nucleosides having miconazole-like scaffolds as imidazole- and pyrimidine-based compounds were examined for their cytotoxic properties. The aim was to establish a relation between cytotoxic activity and nature of the synthetic compounds. While Escherichia coli (DH5α) and human erythromyeloblastoid leukemia cell line (K562) were the target cells, depending on the type of substitution made, ranges of antibacterial and antineoplastic activities were observed. Also the electron-donating and electron-accepting properties of the ligands were proved to play a crucial role in their cytotoxic activities. Accordingly, the substitutions associated with the marked improvement of cytotoxic activities can be considered as the significant point in construction of new generation of either antibacterial or antineoplastic agents.     

Gastric pneumatosis following nasogastric tube placement: a case report with literature review

We report a case of gastric emphysema following placement of nasogastric (NG) tube. Gas in the wall of the stomach is a rare finding seen in various clinical situations. The reported cases fall into two different categories: “gastric emphysema” and “emphysematous gastritis”. Differentiating these two entities is important, as the first one is usually a benign condition, but the second one carries a poor prognosis.     

Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection

BACKGROUND AND OBJECTIVES: Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. STUDY DESIGN/MATERIALS AND METHODS: Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. RESULTS: Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P < 0.001], and in group III (control) [978.92 +/- 87.57; P < 0.003]. Forty-eight hours after the intervention intrahepatic mRNA expression level of HGF in group II (resection) was almost twofold higher than in group I (laser) [7.2 +/- 1.0 c/mf vs. 3.9 +/- 0.4 c/mf; P<0.01]. Fourteen days after the intervention intrahepatic mRNA expression level of CTGF in group I (laser) was higher than in group II (resection) [13.89 +/- 0.77 c/mf vs. 9.09 +/- 0.78 c/mf; P < 0.003]. CONCLUSIONS: LITT leads to a decrease of residual tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT.     

Effect of Processed Oil on Asphalt Binder Properties

This study investigates the effectiveness of processed oil in the modification of PG 64-22 and PG 76-22 by assessing their physical and rheological properties, and multiple comparison was conducted between the two binders. The base binders PG 64-22 and PG 76-22 were blended with processed oil at four different percentages of contents (3%, 6%, 9% and 12% by the weight of the binder) and compared with the control binder in each test. The base and modified binders were artificially short-term and long-term aged using a rolling thin film oven (RTFO) and pressure aging vessel (PAV) procedures. Superpave binder tests were performed on the modified binders by applying a rotational viscometer (RV), dynamic shear rheometer (DSR), and bending beam rheometer (BBR). The comparisons and results presented in this study indicate that (1) the processed oil has a significant effect on the binders’ viscosity, which changes with respect to the increment of processed oil content. The viscosity of both modified binders decreased with the addition of 3, 6, 9 and 12% processed oil; (2) the performed DSR test showed that the addition of processed oil had a negative effect on the rutting resistance for both binders, since in PG 64-22, G*/Sin δ values decreased by 55, 65, 75 and 83% with the addition of 3, 6, 9 and 12% processed oil, respectively, while a decrement of G*/Sin δ of 24, 45, 58 and 65% with the addition of 3, 6, 9 and 12% processed oil was observed in PG 76-22; meanwhile, the fatigue cracking performance was improved and was found to be effective, while G* Sin δ in PG76-22 decreased by 9, 30, 36, and 52% and in PG 64-22 by 27, 44, 53, and 67% with the addition of 3, 6, 9 and 12% processed oil; (3) the results from the BBR test indicate significant improvement in the thermal cracking properties of the binders. The addition of 3, 6, 9 and 12% processed oil resulted in a decrease in the stiffness of both the PG 64-22 and PG 76-22 binders, with a positive effect consequently being observed on the m-values of the binders.     

Is there utility for fluorine-18-fluorodeoxyglucose positron-emission tomography scan before surgery in breast cancer? A 15-year overall survival analysis

BACKGROUNDThe prognostic value of preoperative fluorine-18-fluorodeoxyglucose positron-emission tomography (¹⁸F-FDG PET) scan for determining overall survival (OS) in breast cancer (BC) patients is controversial. AIMTo evaluate the OS predictive value of preoperative PET positivity after 15 years.METHODSWe performed a retrospective search of the Universitair Ziekenhuis Brussel patient database for nonmetastatic patients who underwent preoperative PET between 2002-2008. PET positivity was determined by anatomical region of interest (AROI) findings for breast and axillary, sternal, and distant sites. The prognostic role of PET was examined as a qualitative binary factor (positive vs negative status) and as a continuous variable [maximum standard uptake value (SUVmax)] in multivariate survival analyses using Cox proportional hazards models. Among the 104 identified patients who received PET, 36 were further analyzed for the SUVmax in the AROI. RESULTSPoor OS within the 15-year study period was predicted by PET-positive status for axillary (P = 0.033), sternal (P = 0.033), and combined PET-axillary/sternal (P = 0.008) nodes. Poor disease-free survival was associated with PET-positive axillary status (P = 0.040) and combined axillary/sternal status (P = 0.023). Cox models confirmed the long-term prognostic value of combined PET-axillary/sternal status [hazard ratio (HR): 3.08, 95% confidence interval: 1.42-6.69]. SUVmax of ipsilateral breast and axilla as continuous covariates were significant predictors of long-term OS with HRs of 1.25 (P = 0.048) and 1.54 (P = 0.029), corresponding to relative increase in the risk of death of 25% and 54% per SUVmax unit, respectively. In addition, the ratio of the ipsilateral axillary SUVmax over the contralateral axillary SUVmax was the most significant OS predictor (P = 0.027), with 1.94 HR, indicating a two-fold relative increase of mortality risk.CONCLUSIONPreoperative PET is valuable for prediction of long-term survival. Ipsilateral axillary SUVmax ratio over the uninvolved side represents a new prognostic finding that warrants further investigation.     

Gaps in the management of diabetes in Asia: A need for improved awareness and strategies in men's sexual health

Sexual dysfunction, which is defined as ‘difficulty during any stage of the sexual encounter that prevents or impairs the individual or couple from enjoying sexual activity’, is globally prevalent in males with prediabetes and diabetes. It is an early harbinger of cardiovascular diseases and has a profound impact on one''s physical, mental, and social health. Among patients with either prediabetes or diabetes, the most common male sexual dysfunctions are hypogonadism, erectile dysfunction, and premature ejaculation. In Asia, although sexual health is an important factor of men''s health, it is rarely discussed freely in real‐life practice. Addressing sexual health in Asian males has always been challenging with multiple barriers at the levels of patients and health care providers. Therefore, the assessment and management of sexual dysfunction in routine clinical practice should involve a holistic approach with effective patient–provider communication. In this review, we discuss the epidemiology, pathophysiology, and the management of hypogonadism, erectile dysfunction, and premature ejaculation among males with either prediabetes or diabetes (type 1 and type 2), as well as the evidence gaps across Asia.