Role of Angiotensin II in Fibrous Tissue Formation Following Myocardial Infarction

Traditional views of circulating angiotensin (Ang) II have focused on its endocrine properties in classical target tissues (e.g., kidneys and vasculature), where resident cell populations express Ang II receptors. More recent evidence supports its role in nonclassical tissues (e.g., adipose and connective tissues). Moreover, de novo generation of Ang peptides by cellular constituents of these nonclassical tissues has drawn attention to autocrine and paracrine properties of Ang II mediated by AT1 receptor-ligand binding at these sites. Fibrous tissue formation, regulated by phenotypically transformed fibroblast-like cells termed myofibroblasts, represent such nonclassical tissue and cells. Herein we address a role for local Ang II in tissue repair following myocardial infarction. The article further draws attention to the importance of chronic elevations in circulating Ang II, associated with activation of the renin– angiotensin–aldosterone system, that promote unwanted cardiac fibrosis. Genetic risk for adverse cardiovascular structural remodeling and thereby such events as myocardial infarction, stroke, and hypertension may be related to iterations in genes encoding angiotensin-converting enzyme and angiotensinogen. Potentials for gene therapy that could prevent fibrosis and thereby be cardioprotective are also briefly considered.     

Three-Dimensional Anorectal Manometry Enhances Diagnostic Gain by Detecting Sphincter Defects and Puborectalis Pressure

Digestive Diseases and Sciences - Constipation and fecal incontinence (FI) are common and are often evaluated with anorectal manometry. Three-dimensional high-resolution anorectal manometry (HRAM)...     

Complementary and alternative medicine use in British Columbia--a survey of HIV positive people on antiretroviral therapy

In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected final detailed data on complementary and alternative medicine (CAM) use in their HIV treatment program. This cross-sectional study of 682 participants examines types and determinants of CAM use in this program, and examines adverse effects associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM users in the included population, vitamins/minerals (81%), meditation/yoga (36%), massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines (19%), were most commonly used. Multivariate analysis indicated CAM users were less likely to have low education (AOR=0.51), more likely to be unemployed (AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is common. Both patients and health professionals should be aware of potential toxicities and drug interactions related to the use of CAM and HIV/AIDS treatment.     

Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency

Background. Serotonin can induce proliferation of vascular smooth muscle cells. We assessed the ability of a specific serotonin receptor antagonist, sarpogrelate, to inhibit proliferation of cultured porcine coronary artery smooth muscle cells.

Methods. Cell proliferation and mitotic activity were measured using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide. To determine the effect of sarpogrelate on DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and protein synthesis, radioactive incorporation of ³H-thymidine, ³H-uridine, and ³H-phenylalanine, respectively, was used. Synthesis of DNA was also assessed by flow cytometry with propidium iodide as a fluorochrome.

Results. Serotonin, platelet-derived growth factor, endothelin, and angiotensin II all induced proliferation of porcine coronary artery smooth muscle cells. Sarpogrelate specifically inhibited the serotonin-induced cytokine trigger but did not influence platelet-derived growth factor–, endothelin–, or angiotensin II–induced cell proliferation. Sarpogrelate inhibited the serotonin-induced increase in intracellular free ionized calcium concentration, prevented mitogen-activated protein kinase activation, and down-regulated expression of the protooncogenes c-fos and c-jun. Sarpogrelate acted at the G₁ phase of the cell cycle.

Conclusions. These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts.     

Intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy for choroidal neovascularization in age-related macular degeneration

PURPOSE: To report the outcome for eyes treated with intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN AND PARTICIPANTS: Interventional, consecutive, retrospective case series including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg intravitreal injection of bevacizumab followed by PDT within a 2-week period were reviewed. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and need for retreatment. RESULTS: Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9 (40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes (48%) required only a single combined treatment for CNV resolution at the 12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up required only a single combined treatment. There were no complications such as endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings suggest that eyes treated with both intravitreal injection of bevacizumab and PDT require none to a minimal number of re-treatments to have stabilization of vision, even at 12 months of follow-up. Further investigation with large controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.     

Hemorrhage and pelvic fractures

Hemorrhage is the major cause of death in pelvic fractures. In closed pelvic fractures the bleeding is usually self-limited. In the small number of patients with continuing hemorrhage there may be disruption of a major iliac vessel, which will require immediate exploration and repair. In a few patients continuing hemorrhage is due to disruption of a branch of the hypogastric artery, which may be identified by angiography and controlled by embolization. A management protocol is suggested for these patients.     

Adaptive changes in subcellular calcium transport during catecholamine-induced cardiomyopathy

Rats were injected intraperitoneally with isoproterenol in dosage of 40 mg/kg body weight and heart microsomal and mitochondrial fractions were isolated 3, 9 and 24 h later. The heart/body weight ratio increased at 9 and 24 h after injection without any changes in the yield of subcellular organelles. Microsomal calcium uptake was significantly elevated at 3 h but returned to normal at 9 h and then became depressed 24 h post-injection. Mitochondrial calcium uptake was significantly increased 9 and 24 h after isoproterenol administration. Kinetic parameters of the calcium transport function indicated that the apparent affinity for Ca2+ remained unchanged, whereas Vmax values were altered in the experimental groups. Although there was no significant change in the phospholipid composition, the total phospholipid contents were increased (at 3, 9 and 24 h for microsomes; 3 and 9 h for mitochondria) in both types of organelles. The protein composition, as determined by gel electrophoresis, was altered in microsomes, but not in mitochondria. These results demonstrate rapid structural and functional changes in subcellular organelles. Such alterations may play an adaptive role in maintaining the intracellular calcium homeostasis during the development of catecholamine-induced cardiomyopathy.     

Prevalence of different types of lysosomal storage diseases in saudi arabia

Summary The frequency of different types of lysosomal storage diseases in 125 referred cases, collected over three years, was compared to the occurrence elsewhere. The data suggest that mucopolysaccharidosis (MPS) type IVA (Morquio disease), multiple sulphatase deficiency, Niemann-Pick disease type B, GM2 gangliosidosis type 0 (Sandhoff disease), and ceroid lipofuscinosis (Jansky-Bielschowsky and Batten-Spielmeyer-Vogt syndromes) are encountered frequently in Saudi Arabia, as compared to other storage diseases. In contrast, some other diseases such as the adult variant of Gaucher's disease were not observed. Half of the GM2 gangliosidosis type 0 cases originated from one large tribe in the country. Other conditions did not show tribal predilection. The ceroid lipofuscinosis cases in Saudi Arabia originated from four large families. Consanguineous marriages taking place within tribal boundaries probably account for the pattern observed.     

Incidence and risk factors associated with retinal redetachment after silicone oil removal in the African population

The purpose of this study was to investigate the incidence and risk factors associated with retinal redetachment after silicone oil (SO) removal in the African population. A retrospective cohort study was performed on patients undergoing SO removal over a period of 4 years. The risk factors assessed were (1) characteristics of the retinal detachments including type of retinal detachment, type, number and location of the retinal tears, and proliferative vitreoretinopathy (PVR) score, and (2) surgical factors including type of silicone oil used, use of laser prior to SO removal, and location of the laser (360° or around the tear only). SO was removed either through a pars plana approach or transpupillary approach and anterior limbal incision. Ninety-nine eyes met the inclusion criteria during the study period. Twelve patients (12 %) had retinal redetachment after SO removal. Factors associated with redetachment were a preexisting macular hole, PVR grade B or worse, and no intraoperative endolaser photocoagulation. The incidence of redetachment in African population is similar to that reported from developed countries and other advanced vitreoretinal centers. Redetachment occurred at higher rates in patients with preexisting macular holes and tears who did not receive intraoperative endolaser photocoagulation and patients with a severe grade of PVR.