Journal of Medical Hypotheses and Ideas1Inhibition of corneal neovascularization with new Tyrosine Kinase Inhibitors targeting vascular endothelial growth factor receptors: Sunitinib malate and Sorafenib12Yadollah ShakibaDelnia Arshadi20151005Corneal neovascularization (NV) is a significant, sight-threatening, complication of many ocular surface disorders. Presence of new vessels in cornea can compromise clarity and thus vision. The data supporting a causal role for vascular endothelial growth factor (VEGF) in corneal NV are extensive. Inhibition of VEGF remains as a main strategy for treating corneal NV. There is a growing body of evidence that corneal NV can be reduced by using anti-VEGF agents. Sunitinib malate and Sorafenib are new orally bio-available anti-angiogenic agents undergoing tests of efficacy in the treatment of various types of cancers. The main mechanism of these drugs is inhibiting angiogenesis by diminishing signaling through VEGF receptor1 (VEGFR1), VEGFR2, and platelet-derived growth factor receptors. Since VEGF exerts its angiogenic effects through tyrosine kinase receptors in cornea, any mechanisms which reduce VEGF signaling may inhibit corneal NV or at least attenuate it. Based on this fact we herein hypothesize that Sunitinib malate and Sorafenib can be prepared in topical form and be used in corneal neovascularization states. These approaches offer new hope for the successful treatment of corneal NV. Further investigations in animal models are needed to place these two drugs alongside corneal NV therapeutics.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/1https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/1/1Journal of Medical Hypotheses and Ideas1Suppress or not to suppress gastric acid?Intra-gastric pH monitoring Vs. Litmus paper in critically ill patients23Mansoor RastegarpanahMojtaba Mojtahedzadeh20151005Stress ulceration and gastrointestinal bleeding complicates many clinical illnesses in patients in the intensive care unit (ICU). We hypothesized that suppression of gastric acid and monitoring of gastric pH using intra-gastric pH monitoring can be beneficial to critically ill patients. To test this idea we have performed a pilot study to compare the accuracy of litmus paper to determine gastric pH to a nasogastric platin-antimony pH probe in a teaching hospital in Tehran. Twenty critically ill patients in intensive care unit who required stress ulcer prophylaxis, by using a crossover design the patients randomized to initially received ranitidine by continuous infusion or intravenous bolus and subsequently were crossed over to the other arm of the study. Gastric pH was determined using pH sensitive litmus paper at the initiation of each arm of the study and at 1, 2, 4 and 8 hours after the initiation of ranitidine. In addition, gastric pH was continuously determined over the same time utilizing a platin-antimony pH probe made in Iran.
Pilot Results of gastric pH measurement determined with litmus paper and intra-gastric pH probes demonstrated by regression analysis comparing these two methods showed a good correlation between the two methods (r=0.7). The pH probe technique for intra-gastric pH measurement appears to be technically simple and clinically applicable for use on patients at risk for stress ulcer bleeding. It may be more accurate than litmus paper in patient receiving H2 antagonists. Further investigations are needed to validate this idea.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/2https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/2/2Journal of Medical Hypotheses and Ideas1Creating an entire community covering population based injury registration system: a developed country perspective34Tanvir ChowdhuryTurin Nahid Rumana20151005The public-health approach to injury prevention and control includes epidemiological assessment, development of prevention strategies, and evaluation of these strategies. Injury-surveillance systems should be capable of providing essential information for each of these elements. The scale of injury problem is not a matter of dispute. The costs of injury mortality and morbidity are immense not only in terms of lost economic opportunity and demands on national health budget but also in terms of personal and social sufferings. Despite this, few countries have comprehensive surveillance system that generates reliable information on the nature and extent of injuries, especially with regards to non-fatal injuries. Without reliable information health care planners are severely handicapped. They are unable to allocate resources efficiently in order to achieve the greatest impact in preventing injuries. This is true for planners at all levels, whether they are concerned with the world wide injury problem or national, regional or local level injury problems. Injury registries are indispensable in determining the incidence and trends in a particular population. A registry complements the cross-sectional studies of the differences in disease rates by longitudinal investigation. The initiation of the simultaneous monitoring of the incidence, mortality, morbidity, risk factor levels, social and behavioral tendency within defined community over a period of years will help in clarify the interrelation between these variables in terms of the dynamics of change in the natural history of injury trend. Information of injury occurrences and risk factors in population is very essential and surveillance provides this essential information that can be used for designing effective prevention strategies, appropriate allocation of health resource, assessment of effectiveness of the health programs, etc. The purpose of this registration is to follow the injury incidence and mortality trend in Japan using a whole community population covering registry that serve to most up to date information.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/3https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/3/3Journal of Medical Hypotheses and Ideas1The pharmacogenetics of cytochrome P450 enzymes in personalized medicine45Majid Moridani20151005Personalized medicine is partially enabled by in vitro diagnostics including pharmacogenomic, proteomic and other functional testing such as therapeutic drug management and toxicological testing. This paper will introduce the conceptual aspects of developing personalized treatment using pharmacogenetics information. The initial discussion will give an overview of the application of pharmacogenetics in personalized medicine, followed by specific examples involving cytochrome P450s drug metabolizing enzymes (CYP enzymes). The paper also discusses the influence of racial and ethnic characteristics of a population on the variation in drug effectiveness and toxicity. The need for implementation of pharmacogenetics in medical education is highlighted.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/4https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/4/4Journal of Medical Hypotheses and Ideas1Modified retention enema, possible cure for solitary rectal ulcer56Mohammad VafaeiSaeed DerakhashaniBehzad Elahi20151005Since ancient times, enemas have been used in various clinical scenarios. It was used as a way to relieve constipation, administration of analgesia and anesthesia in children, pre-operative bowel preparation, control of fever and seizures, post-operative analgesia, and the treatment of acute pancreatitis, hepatic encephalopathy and hyperkalemia. We believe clinical application of this modified retention enema can benefit patients suffering from solitary rectal ulcer syndrome (SRUS). Our hypothesis is to prove superiority of combination therapy to conventional therapies for Mucosal Prolapse Solitary Rectal Ulcer Syndrome (MPSRUS). Our modified retention enema has active components that improve inflammation, protects mucosa and explained method of administration will also improve mucosal blood perfusion. This will result in clinical and histological healing of the SRUS.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/5https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/5/5Journal of Medical Hypotheses and Ideas1Possible effect of dihydropyridines on topoisomerase-mediated multidrug resistance, a new approach for ِdesigning the new reversal agents for atypical MDR67Ahmadreza MehdipourKatayoun JavidniaBahram HemmateenejadRamin Miri20151005Multidrug resistance can result from several factors and processes. Some types of multidrug resistance (MDR) were recognized whose patterns differ from pattern of P-glycoprotein (P-gp) associated MDR in several important ways. Although, there is limited evidence for effect of DHP on atypical MDR; based on some observations like noncompetitive inhibition of topoisomerase I by a DHP derivative (Dexniguldipine), it has been hypothesized that some DHP derivatives which have essential structural feature have possible effect on altering the topoisomerase II levels or activity which results in reversing topoisomerase-mediated MDR. If this hypothesis is verified, some new dihydropyridine can be synthesized with possible dual effect on both typical and atypical MDR.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/6https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/6/6Journal of Medical Hypotheses and Ideas1Effects of noxious compounds in exhaled breath air as a potential mechanism causing "Red eye" in renal failure patients78Alireza GhaffariyehTooraj Chamacham20151005Renal failure can lead to the retention of nitrogenous waste products which affects almost all organ systems in human body and causes complex clinical manifestations. Eye can be one of these affected organs. "Red eye" is not an uncommon complication of renal failure. Over the past several decades numerous theories have attempted to describe the possible pathogenic pathways leading to the diverse ocular complications of renal failure. Some of the retained waste products in renal failure such as, nitric oxide, hydrogen peroxide and methylamines can be elaborated and exhaled via breath air. We hypothesize that the effects of these exhaled noxious compounds on the ocular surface over an extended period of time can be considered as another potential mechanism contributing to ocular manifestations, particularly the "red eye", in renal failure.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/7https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/7/7Journal of Medical Hypotheses and Ideas1Down regulation of NF-kappa B as a therapeutic strategy for type 1 diabetes: effect of flavonoids89Amin ArdestaniRazieh Yazdanparast20151005Nuclear factor-kappa B (NF-κB) is a redox-sensitive transcription factor that plays a critical role in the regulation of a variety of genes important in cellular responses, including inflammation, innate immunity, growth, and cell death. There are growing evidences that activation of NF-κB by acute oxidative stress may be the critical signal initiating the cascade of events leading to β-cell death and type 1 diabetes. This activation results in an increase in inflammatory and immune responses and leads to an amplification of reactive oxygen species (ROS) and nitric oxide (NO) production which, in turn, ultimately leads to the destruction of the β-cells, hyperglycemia and the development of type 1 diabetes. The key role of NF-κB in controlling the expression of multiple inflammatory and immune genes involved in type 1 diabetes makes this factor as a central and favorable target for therapeutic intervention of this disease. Polyphenolic plant-derived flavonoids display characteristic inhibitory patterns toward the NF-κB signal transduction pathways. In various types of cells, flavonoids, as natural polyphenolic antioxidants, strongly block cytokine- or LPS-induced NF-κB activation, which is crucial for iNOS expression in β-cells. Recently, we have suggested that a number of flavonoids might exert protective effects on pancreatic β-cell and therefore this could be considered as potential therapeutic agents for type 1 diabetes. On the other hand, studies investigating cytokine-induced pancreatic β-cells death models of type 1 diabetes, have found that flavonoids are effective for type 1 diabetes at least partly through inhibition of NF-κB activation. The importance of NF-κB in β-cell inflammatory responses is underscored by the fact that blockade of NF-κB in in vitro and in vivo models, by means of flavonoids, may prevents β-cell destruction and type 1 diabetes. In view of their anti-inflammatory and antioxidant abilities and their capacity to modulate NF-κB signaling pathways, it is hypothesize that flavonoids hold great promise as potential therapeutic agents for controlling the onset of type 1 diabetes.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/8https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/8/8