Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate B, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty.     

Screening applications for MRI in the detection of upper abdominal disease: comparative study of non-contrast-enhanced single-shot MRI and contrast-enhanced helical CT

Purpose: To compare the value of ’push-button' singe-shot non-contrast-enhanced MRI and contrast-enhanced helical CT for detection of upper abdominal disease. Methods: In 120 patients, images obtained with non contrast-enhanced single-shot MRI (T2: double echo HASTE, and T1: turbo FLASH) and contrast-enhanced helical CT were compared. Lesions or abnormalities were divided in 8 anatomical categories (1: liver; 2: pancreatobiliary; 3: kidney/adrenal gland; 4: retroperitoneum; 5: vascular; 6: spleen; 7: gastrointestinal tract and peritoneum; 8: base of thorax) and classified as follows: 2: seen at MRI only; 1: better seen at MRI; 0: no difference; −1: better seen at CT; −2: seen at CT only. Also recorded were the 'door-to-door’ examination times. Results: Of a total of 629 abnormalities, 594 were detected at MRI (94 %) and 536 at CT (85 %). CT offered better results in two categories only: retroperitoneum (mean score: −0.68) and vascular (mean score −0.87). Mean examination times were 19 min for CT and 14.8 min for MRI. Conclusion: Unenhanced single-shot MRI is a valuable first step of a comprehensive upper abdominal MR exam and may even be the final step in many patients. Received: 3 April 1998; Revision received: 13 July 1998; Accepted: 18 August 1998     

Impact of radiotherapy for localized prostate cancer on bladder function as demonstrated on urodynamics study: A systematic review

IntroductionThis study aimed to describe the effects of bladder function following radiotherapy for localized prostate cancer by performing a systematic review on studies reporting on urodynamic findings after radiotherapy.MethodsThis systematic review was conducted in accordance with PRISMA guidelines. The review protocol was registered at PROSPERO (CRD42021229037). A systematic search was conducted using PubMed, Cochrane Library, Scopus, and OVID Embase. Studies were included if they involved men who underwent urodynamic studies following radiotherapy for localized prostate cancer. A total of 798 articles were screened and five articles included. A qualitative analysis was performed.ResultsBladder compliance appears to be impaired following radiotherapy, especially with longer followup. Impaired bladder compliance was reported in 18.8–62.5% of patients following radiotherapy. Bladder capacity was found to be statistically significantly lower following radiotherapy compared to pre-radiotherapy, and when compared with patients who did not undergo pelvic radiotherapy. Bladder outlet obstruction (BOO) persists post-radiotherapy in most patients at three and 18 months post-radiotherapy. De novo detrusor overactivity (DO) of 13.3% has been reported at 18 months post-radiotherapy. This review is limited by the absence of level I/II studies.ConclusionsRadiotherapy for localized prostate cancer results in decreased bladder compliance and capacity demonstrated on urodynamic studies. Resolution of BOO appears less likely in comparison to series on radical prostatectomy. De novo DO may develop following radiotherapy, especially with longer followup. With only low level of evidence studies available at present, further high-quality, prospective studies are important to elucidate the impact of radiotherapy on bladder and urethral function.     

Prediction of overall survival following colorectal cancer surgery in elderly patients

BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC) becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surgery for these elderly patients can be challenging.An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients.AIM To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system.METHODS In this retrospective cohort study,patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database.Patients with evidence of metastatic disease,and those who underwent emergency surgery or had surgery for benign colorectal conditions wereexcluded from the analysis.The primary outcome was overall 3-year overall survival(OS) following surgery.A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital,South Korea.Statistical analyses were performed using Stata/MP Version 15.1.RESULTS A total of 1267 patients were identified for analysis.The median post-operative length of stay was 8 [interquartile range(IQR) 6-12] d and median follow-up duration was 47(IQR 19-75) mo.Median OS was 78(IQR 65-85) mo.Following multivariate analysis,the factors significant for predicting overall mortality were serum albumin 35 g/dL,serum carcinoembryonic antigen ≥ 20 μg/L,T stage 3 or 4,moderate tumor cell differentiation or worse,mucinous histology,rectal tumors,and pre-existing chronic obstructive lung disease.Advanced age alone was not found to be significant.The Korean cohort consisted of 910 patients.The Singapore cohort exhibited a poorer OS,likely due to a higher proportion of advanced cancers.Despite the clinicopathologic differences,there was successful validation of the model following recalibration.An interactive online calculator was designed to facilitate post-operative survival prediction,available at http://bit.ly/sgh_crc.The main limitation of the study was selection bias,as patients who had undergone surgery would have tended to be physiologically fitter.CONCLUSION This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process.Validation with an external population strengthens the generalizability of this model.     

South‐East Asia study alliance guidelines on the management of acne vulgaris in South‐East Asian patients

The management of acne in South‐East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first‐line treatment (a 6‐ or 8‐week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use.     

Glioma gene therapy using induced pluripotent stem cell derived neural stem cells

Using neural stem cells (NSCs) with tumor tropic migratory capacity to deliver therapeutic genes is an attractive strategy in eliminating metastatic or disseminated tumors. While different methods have been developed to isolate or generate NSCs, it has not been assessed whether induced pluripotent stem (iPS) cells, a type of pluripotent stem cells that hold great potential for regenerative medicine, can be used as a source for derivation of NSCs with tumor tropism. In this study, we used a conventional lentivirus transduction method to derive iPS cells from primary mouse embryonic fibroblasts and then generated NSCs from the iPS cells. To investigate whether the iPS cell derived NSCs can be used in the treatment of disseminated brain tumors, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected into the cerebral hemisphere contralateral to a tumor inoculation site in a mouse intracranial human glioma xenograft model. We observed that NSCs expressing the suicide gene were, in the presence of ganciclovir, effective in inhibiting the growth of the glioma xenografts and prolonging survival of tumor-bearing mice. Our findings provide evidence for the feasibility of using iPS cell derived NSCs as cellular vehicles for targeted anticancer gene therapy.     

Ectopic gastric pancreatitis: unusual cause of epigastric pain

Ectopic pancreatic tissue has the same characteristics than normal pancreatic tissue.Therefore it may be affected by the same diseases. We report a rare cause of epigastric pain due to gastric heterotopic pancreatitis.The rare diagnosis was suspected by ultrasound and CT and definitively confirmed by echo-endoscopic guided biopsies.