Visual acuity and foveal thickness after vitrectomy for macular edema associated with branch retinal vein occlusion: a case series

Abstract Background The mechanism by which vitrectomy improves macular edema in patients with branch retinal vein occlusion remains unclear, although intraocular levels of vascular endothelial growth factor have been suggested to influence the visual prognosis and macular edema. Methods A series of 54 consecutive patients (54 eyes) with branch retinal vein occlusion was studied prospectively. All patients underwent pars plana vitrectomy for treatment of macular edema. Best corrected visual acuity and retinal thickness (examined by optical coherence tomography) were assessed before and after surgery. The level of vascular endothelial growth factor in vitreous fluid harvested at operation was determined. Patients were followed for at least 6 months postoperatively. Results Both the visual acuity and the retinal thickness showed significant improvement at 6 months postoperatively (P = 0.0002 and P Conclusions These results suggest that the vitreous level of vascular endothelial growth factor might influence the visual prognosis and the response of macular edema to vitrectomy in patients with branch retinal vein occlusion.</p

Suppression of uPA and uPAR Attenuates Angiogenin Mediated Angiogenesis in Endothelial and Glioblastoma Cell Lines

In our earlier reports, we showed that downregulation of uPA and uPAR inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited angiogenesis in nude mice. The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood.In the present study, we have attempted to investigate the mechanism by which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and glioblastoma cell lines. uPA/uPAR downregulation by shRNA in U87 MG and U87 SPARC co-cultures with endothelial cells inhibited angiogenesis as assessed by in vitro angiogenesis assay and in vivo dorsal skin-fold chamber model in nude mice. Protein antibody array analysis of co-cultures of U87 and U87 SPARC cells with endothelial cells treated with pU2 (shRNA against uPA and uPAR) showed decreased angiogenin secretion and angiopoietin-1 as well as several other pro-angiogenic molecules. Therefore, we investigated the role of angiogenin and found that nuclear translocation, ribonucleolytic and 45S rRNA synthesis, which are all critical for angiogenic function of angiogenin, were significantly inhibited in endothelial cells transfected with uPA, uPAR and uPA/uPAR when compared with controls. Moreover, uPA and uPAR downregulation significantly inhibited the phosphorylation of Tie-2 receptor and also down regulated FKHR activation in the nucleus of endothelial cells via the GRB2/AKT/BAD pathway. Treatment of endothelial cells with ruPA increased angiogenin secretion and angiogenin expression as determined by ELISA and western blotting in a dose-dependent manner. The amino terminal fragment of uPA down regulated ruPA-induced angiogenin in endothelial cells, thereby suggesting that uPA plays a critical role in positively regulating angiogenin in glioblastoma cells.Taken together, our results suggest that uPA/uPAR downregulation suppresses angiogenesis in endothelial cells induced by glioblastoma cell lines partially by downregulation of angiogenin and by inhibition of the angiopoietin-1/AKT/FKHR pathway

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

Vitamin A derivatives in the prevention and treatment of human cancer.

Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy

Production and investigation of the effects of polysaccharide-protein conjugate vaccine in prevention of Salmonella Typhimurium infection in mouse model

S.Typhimurium is a gram negative bacterium causing serious enteric or extraintestinal infections in human, cattle and birds. These kinds of infections may lead to some permanent or non-permanent complications like endophthalmitis, Guillain-Barre syndrome and osteomyelitis. Multi-resistant strains of S.Typhimurium have been reported from several countries, and these infections are a major public health problem throughout the world. The aim of the present study was to develop a conjugate vaccine for prevention of S.Typhimurium infections. For this purpose, polysaccharide side chain was conjugated with tetanus toxoid by carbodiimid mediated amidation method. Immunodiffusion was performed in agarose gel. 4 groups of BALB/c mice were selected and immunized with heat killed S.Typhimurium, purified polysaccharide, polysaccharide side chain-tetanus toxoid conjugate and sterilized distilled water and the role of each antigen in protection against infection with pathogenic S.Typhimurium were investigated. Animals were challenged by intraperitoneal injections. The 50% lethal dose (LD50) was determined on the 21st post-challenge day by Reed and Muench method. Immunodiffusion results showed that the conjugate reacted with heat killed whole all vaccine anti-serum and tetanus toxoid anti-serum. 3 injections of conjugate caused protection against intraperitoneal challenge. In conjugate immunized group LD50 increased 15.4 and 11.11 fold in comparison to control group and polysaccharide side chain immunized group respectively. Results showed that polysaccharide side chain-tetanus toxoid conjugate injected in 3 doses is very protective in mice and can increase the LD50 of immunized animals significantly in comparison to both O antigen vaccinated and control groups. Keywords: S.typhimurium, Lipopolysaccharide, Conjugate vaccin

Evaluation of physiology knowledge loss in medical students of Ahvaz Jundishapur University of Medical Sciences

Narjes Zaeemzadeh,1 Sanaz Taherpour,2 Noor Behzadian,2 Seyyed Ali Mard2 1Deparment of Phamacology, The School of Pharmacy, Medical Educational and Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Physiology Research Center (PRC), Department of Physiology, School of Medicine, Medical Educational and Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Purpose: The knowledge loss or longevity of taught lessons is a major concern in medical students and all medical practitioners. This study evaluated the physiology knowledge loss in medical students in Ahvaz Jundishapur University of Medical Sciences in Iran. Methods: A total of 265 volunteers from medical students who had previously passed the &ldquo;general exam of medical basic sciences&rdquo; at the end of fifth semester took a retention test (RT) to evaluate their knowledge loss of physiology. The candidates were divided into ten groups depending on the semester (S) they were passing at the time of study: 41 students in preclinical levels (S6 and S7), 123 students in externship levels (S8, S9, S10, S11 and S12), and 101 students in internship levels (S13, S14 and S15). The RT consisted of 20 multiple choice questions from all topics of medical physiology, including central nervous system, endocrine, gastrointestinal, cardiovascular, respiratory, renal, blood, and cellular. Results: Findings showed that there was a decreasing trend of knowledge loss from S6 to S15. The lowest level of knowledge loss was observed in S15 students. These results also demonstrated that knowledge loss in male medical students was more than that in female students. Conclusion: These findings indicated that the physiology knowledge loss trend is inversely correlated with the time passing. We conclude that the reason is that physiology is a basic science which is most applicable during medical students&rsquo; clinical years. Keywords: Ahvaz, Iran, medical students, physiology, knowledge loss, retention test, female studen

Mitigation options for futurewater scarcity: A case study in Santa Cruz Island (Galapagos Archipelago)

Santa Cruz Island (Galápagos Archipelago), like many other tourist islands, is currently experiencing an exponential increase in tourism and local population growth, jeopardizing current and future water supply. An accurate assessment of the future water supply/demand balance is crucial to capital investment for water infrastructure. This paper aims to present five intervention strategies, which are suggested to solve the future water crisis. The strategies combined include environmentally sustainable options such as rainwater harvesting, greywater recycling and water demand management, as well as desalination. These strategies were evaluated under four population growth scenarios (very fast, fast, moderate and slow growths) by using several Key Performance Indicators (KPI’s) including water demand, leakage levels, total costs, energy consumption, rainwater delivered and greywater recycled. Moreover, it also aims to develop a methodology for similar islands, using the WaterMet2 modelling approach, a tool for integrated of sustainable-based performance of urban water systems. The results obtained show that by 2044 only a small portion of the future water demand can be covered assuming business as usual. Therefore, desalination seems to be the most viable option in order to mitigate the lack of water at the end of the planning period considering the growth trends. However, strategies comprising more environmentally friendly alternatives may be sufficient, but only under slow population growth scenarios