Journal of Medical Hypotheses and Ideas4ONE-TWO Criteria: Improving the Approach to Electrocardiogram7070MotaharsadatHosseiniSayed ShahabuddinHoseiniNasrinShoarSaeedShoar20151005The electrocardiogram (EKG) is one of the major Para-clinic exams for evaluating patients suspected to cardiac or non-cardiac disease which could be very informative especially when assessed by experienced clinicians. To improve and accelerate the approach to EKG interpretation, simple and accurate criteria are useful and save the physician's time especially in emergent situations.In this article, we introduce our criteria which determine whether the electrical axis of heart is normal or not and if abnormal, what kind of deviation it has. These criteria say that "if the mean QRS complex in leads I and II are positive, the axis will be accurately in the normal range (-30 to +90); unless, the axis is abnormal necessitating a more complex evaluation". These criteria could simplify the first step of the approach to EKG interpretation especially in emergent situations. They can also be proper substitute for current methods of heart axis determination in clinical practice and for educational goals.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/70https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/70/70Journal of Medical Hypotheses and Ideas4Topical Application of Vitreous Body as a New Alternative for the Treatment of Persistent Epithelial Defect and Dry Eye7171Hamid RezaJahadi HosseiniMahmoodNejabatMohsenFarvardinMahnazMosallaei20151005Many growth factors and chemical agents were previously used to accelerate corneal epithelial wound healing and dry eye .One of the enriched substances is autologous blood introduced with multiple randomized controlled studies for those who are not responsive to conventional treatments. Vitreous body as a natural substance has some properties which seem to make it superior to authologous blood for the management of severe dry eye syndrome and even persistent epithelial defect. This theory is based on some clues listed as below:Vitreous contains a high amount of water and little macromolecules, the character suitable for a substance to be used for relieving symptoms of dry eye as a wetting effect. Moreover, it contains some growth factors such as insulin like growth factors and pigment epithelium-derived factor and high amount of viscous materials such as Chondroitin Sulfates and Hyaloronic acids, all are compounds seems to be effective in the management of dry eye and acceleration of epithelialization. It has also anti-inflammatory features. The most important unique feature of vitreous in comparison with blood is its immune privilege property documented by previous studies. Vitreous can be obtained from brain dead patients and also from eye banks easily. As with all transplanted material of human origin, it carries risks of prion transmission; however, for intractable severe dry eye, benefits may greatly exceed the risk.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/71https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/71/71Journal of Medical Hypotheses and Ideas4Cannabinoid (JWH-133) therapy could be effective for treatment of corneal neovascularization7272MaryamKeshavarzAmir HosseinNorooznezhadKamranMansouriAliMostafaie20151005Neovascularization of the normally avascular cornea was associated with a notable increase in the expression of the major proangiogenic factors and proteases. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Anti-angiogenic therapy is considered as a possible tool for controlling corneal neovascularization. Endocannabinoids are now considering as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancers. JWH-133 as a CB2 selective ligand is one of the pharmacological cannabinoid derivatives that could induce apoptosis and reduce secretion of major stimulatory factors involved in cell proliferation and angiogenesis. Several studies have indicated that JWH-133 inhibit tumor angiogenesis in vitro and in vivo through direct inhibition of vascular endothelial cell migration and survival, as well as suppression of proangiogenic factor and MMP-2 expression.Based on the present information about inducing factors involved in corneal angiogenesis and pharmacological properties of cannabinoids, we hypothesize that topical application of JWH-133 is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. The potential use of JWH-133 in other eye related reports is even more appealing considering that it could be a good safety profile for retarding corneal neovascularzation. However, further investigations in animal models are needed to place JWH-133 alongside corneal neovascularization therapeutics.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/72https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/72/72Journal of Medical Hypotheses and Ideas4Dose L1 Retrotransposition Cause Neuronal Loss in Neurodegenerative Disorders?7373LalehHabibiSeyed MohammadAkramiMohammad AliShokrgozar20151005Neurodegenerative disorders are among debilitating diseases that could affect many aspects of patient's life. Several mechanisms were shown to be involved in neuronal degeneration. However, the direct role of genomic instability is little considered in such disorders. L1 retrotransposons could cause genomic instability in different ways. Studies have shown increasing in L1 retrotransposition due to some reagents like heavy metals, stressors and the ones that may cause neuronal degeneration; Therefore cause cell to die. On the other hand, L1s retrotransposition was shown in neuronal precursor cells (NPCs) providing the first evidence for movement of theses elements in nervous system.Here, we propose that stimulation of L1 retrotransposition by environmental and genetic factors in neurons of central nervous system may lead them to apoptosis and result in neurodegenerative disorders. This hypothesis will be verified using L1-RP vector transfecting to definite neuronal cell line. By adding toxic agents including oxidative stress reagents and heavy metals to cell culture, we may track L1 retrotransposition and effects of this movement on cell physiology. Finding the involvement of mechanism in neurodegeneration may result in inventing new drugs for these disorders.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/73https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/73/73Journal of Medical Hypotheses and Ideas4Magnesium sulphate as a treatment of acute attack of multiple sclerosis7474NohaAbokrysha20151005The blood-brain barrier (BBB) is a complex organization of cerebral endothelial cells. Deregulation of the BBB is among the earliest cerebrovascular abnormalities seen in multiple sclerosis (MS).Magnesium sulfate has been shown to have a protective effect on BBB integrity in multiple experimental models. Magnesium sulphate attenuates BBB permeability. Also, results of light microscopy and electron microscopy verified that magnesium sulfate can attenuate BBB injury. I suggest using of MgSO4 which attenuates BBB permeability during acute relapses of MS. The hypothesis should be assessed in several experimental and clinical trials. If my hypothesis can be verified experimentally and clinically, then using Mg sulphate to treat MS disease could be achieved.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/74https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/74/74Journal of Medical Hypotheses and Ideas4Gold nanoparticles combined with highly expressed amber suppressor tRNA: a future antibacterial agent7575XiaodaSongJingjingSunHongTianXiangdongGao20151005Amber suppressor tRNA is a mutant allele coding for a tRNA, whose anticodon is altered in such a way that the suppressor tRNA inserts an amino acid at an amber codon in translation which leads to suppressing (preventing) termination. And some Amber suppressor tRNA strains were found. We propose that gold nanoparticles combined with highly expressed amber suppressor tRNA which can be uptake by cells and recognized by AARS (aminoacyl tRNA synthetase) will lead to the formation of C-terminally extended proteins. These proteins probably will not work properly, leading bacteria's death. Because of the difference of tRNA between prokaryotic and eukaryotic cells, even between different bacteria species, this amber suppressor tRNA is orthogonal for other species and cannot be recognized by AARS, therefore has no toxicity to other species. May it be an excellent antibacterial agent in the future? In this article we provide a screening method for the highly expressed amber suppressor tRNA using randomly bases mutation, radioactive selection, activity test in vivo, and finally linkage of the amber suppressor tRNA to gold nanoparticles.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/75https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/75/75Journal of Medical Hypotheses and Ideas4Neuroprotection in Parkinson's Disease: a Multi-directional Genetic Strategy for Maximum Protection of Dopaminergic Neurons against Parkinsonian Toxicity7676MossaGardanehYasinPanahiSaharShojaeiElhamMazaheri-TehraniNaderMaghsudi20151005The complex biology of Parkinson's disease and the obscure mechanism of dopaminergic cell death in the course of the disease indicate that multiple intracellular pathways and numerous crucial elements contribute to the demise of these neurons. Therefore, multi-factorial approaches would more likely confer long-lasting survival and potentiate the biological function of dopamine neurons. We are proposing a multi-directional strategy to protect dopamine neurons against parkinsonian toxicity that involve transcription, anti-oxidant and neurotrophic factors. Specifically, Nurr1 an important DA transcription/ anti-inflammatory factor, glutathione peroxidase-1 an anti-oxidant enzyme (GPX-1) and glial cell line-derived neurotrophic factor (GDNF) a potent neurotrophic factor have all shown their capacity for dopaminergic neuroprotection. A model we are proposing is based on dopamine neuron-astrocyte-microglia co-culture that will supply all three factors in a tripartite fashion accelerating gene-to-gene and cell-to-cell cross-talks for synergy. While microglia will overexpress Nurr1, astrocytes will act as minipumps to secrete GDNF into the medium to act on GPX-1-overexpressing dopamine neurons growing within their proximity. The neurons will ultimately be exposed to the parkinsonian neurotoxin 6-OHDA and tested for their improved survival rate in vitro and in vivo, their integration capacity to neural network and their physiological function in the midbrain circuitry.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/76https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/76/76Journal of Medical Hypotheses and Ideas4Electro-acupuncture could be an effective pretreatment for cerebral ischemia7777FengZhangYiWuJieJiaQing-ChuanGuoYong-ShanHu20151005Electroacupuncture, the integration of traditional Chinese acupuncture and modern electrotherapy, has been used for clinical treatment of cerebral ischemic disease in both eastern and western countries; however, the mechanism underlying its effects is still unknown. It is well known that excessive glutamate results in neuronal excitotoxicity after ischemic stroke. Previous studies have indicated that electro-acupuncture may downregulate the overactivation of glutamate after ischemia, and a recent study implied that electro-acupuncture prior to ischemia could induce brain ischemic tolerance. Based on the present information, we hypothesize that electro-acupuncture could be an effective pretreatment for cerebral ischemia by regulating the glutamatergic system.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/77https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/77/77Journal of Medical Hypotheses and Ideas4Cancer cells: novel expression systems in pharmaceutical biotechnology7878Sayed ShahabuddinHoseiniMotaharsadatHosseiniSaeedShoar20151005Every day, numerous medications are used worldwide to treat different kinds of diseases. A huge part of drug manufacturing - is done in pharmaceutical biotechnology companies. Scientists have developed a variety of methods to synthesize these substances. They can insert the gene or the cDNA of a desired protein into special expression systems and extract the resulted products using different methods. The paraneoplastic syndromes are signs and symptoms originated from cancer cell derived products and not because of direct invasion of tumor cells or metastasis. Cancer cells can secret a wide variety of products such as growth hormones, antibodies and so on. In an innovative route, these products may be processed further and eventually be used as useful biologic substances. In this manuscript, we described a process by which scientists can use cancer cells in order to produce various types of biological substances which can be used as medications, diagnostic substances and research materials. Our hypothesis has been inspired from autonomous production of biologic substances from those cancer cells that are responsible for manifestations of paraneoplastic syndromes.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/78https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/78/78Journal of Medical Hypotheses and Ideas4A novel combinatory paradigm for chronic hepatitis C treatment using liver-targeted carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir7979MahshidForoozeshAbdolhosseinZarrin20151005Despite outstanding developments in medical knowledge and technologies, Hepatitis C virus (HCV) affecting almost 180 million people worldwide, is still described as "a serious global health crisis" and its standard of care (combination therapy with pegylated interferon alpha and ribavirin) is just effective in at most 50% of all patients. This suboptimal efficacy and apparent side effects underscore the need for "new anti-HCV agents", "novel combination strategies" and "smart delivery systems". As a response to the urgent need for new anti-HCV drugs, specifically targeted antiviral therapy agents for HCV (STAT-C) has gained many interests these years. Considering the obligation of multidrug therapy in HCV infection and the results of clinical trials, STAT-C will probably supplement interferon/ribavirin combination. Boceprevir as a HCV protease inhibitor is among the most widely studied STAT-C compounds with promising results in clinical trials. Thus, its combination with current double therapy paradigm would be an alternative combination strategy in the treatment of hepatitis C. On the other hand, drug carriers has now evoked much attentions as new trends to increase the efficacy of available therapies by protecting the therapeutic agents from unwanted reactions and/or targeting them directly to their site of action. Carrier erythrocytes are among the most widely studied cellular and particulate carriers suitable for targeted delivery of various drugs to reticuloendothelial system organs like liver, but, with no report about their application for HCV-targeted therapy. Since the majority of recent efforts are focused on new agents' discovery/development and alternative combinations and no reports are available on targeted delivery of double and/or triple drug combinations directly to the liver, an idea has been raised that combination of all 3 approaches mentioned earlier (a completely combinatory paradigm addressing all 3 mentioned needs by one system i.e. the "new anti-HCV agents" in a "novel combination" delivered to its site of action via a "smart delivery system") may have more promising results and reduce the shortcomings of recent approaches. This idea has led us to hypothesize that carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir by means of hypotonic preswelling encapsulation method with post-loading modifications of obtained drug-carriers, could be an appropriate liver targeted-triple combination therapy for HCV particularly in difficult patients (non-responders, co-infected patients with HIV and the ones with decompensated liver disease). Another advantage of this combinatory paradigm is the possibility of co-encapsulation of other agents which gives this strategy a flexibility to be tailored for individualized therapy.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/79https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/79/79Journal of Medical Hypotheses and Ideas4A non-invasive estimate of glomerular filtration rate derived from nonequilibrium thermodynamics8080SimonBrown20151005Acute kidney injury is characterised by elevated serum creatinine and reduced urine output, both of which reflect reduced glomerular filtration rate (GFR). The estimation of GFR is usually obtained from an empirical expression based on the serum creatinine concentration, although other analytes are also used. The selection of the ‘best' analyte and expression has been the subject of much debate. The thermodynamic foundation of GFR leads to an expression for GFR in terms of urine volume and osmotic potential, both of which are easily and non-invasively measured. This expression is consistent with at least some of the data in the literature and provides insight into some of the apparent inconsistency in the relationship between GFR and urine volume. While more complete data are required to evaluate it thoroughly, the expression complements the analyte-based methods for estimating GFR.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/80https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/80/80Journal of Medical Hypotheses and Ideas4Novel theory for treatment of presbyopia: Rejuvenation of zonular fibers by capsular anterior annular peripheral shrinkage (CAPS)8181AlirezaGhaffariyehMohsenShahinpoorDavidSoltanpourNazafarinHonarpisheh20151005Presbyopia is the gradual age-related loss of accommodation. The precise mechanism responsible for presbyopia has not been clearly defined. Recently, Schachar has proposed a radically different theory of accommodation. Schachar theorizes that presbyopia could be corrected if the ciliary muscles could be stretched a small amount to allow them to function on the lens. We propose laser correction of presbyopia with capsular anterior annular peripheral shrinkage is a possible treatment for augmenting the transmission of the contraction force of the ciliary muscle through the zonular fibers to the lens capsule. The resulted shrinkage increase the distance between the lens equator and ciliary muscle leading to restoring the adequate zonular fibers tension and reversing the effect of age-related lens growth on the near vision.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/81https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/81/81Journal of Medical Hypotheses and Ideas4Letter to the editor: A non-invasive estimate of glomerular filtration rate derived from nonequilibrium thermodynamics8282VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/82https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/82/82Journal of Medical Hypotheses and Ideas4Letter to the editor: Estimation of glomerular filtration rate based on thermodynamic principles8383SimonBrown20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/83https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/83/83Journal of Medical Hypotheses and Ideas4A Safe, Versatile and Translation-prone Strategy for Using Circulating Lipoproteins as Endogenous Drug Delivery Systems8484MahshidForoozeshAbdolhosseinZarrin20151005Lipoproteins (LPs), the endogenous lipid-protein micro- and nanostructures involved in lipid metabolism, have attracted a high degree of interest in recent years for being used as novel drug delivery systems. Numerous diagnostic and therapeutic agents (in particular anti-cancer agents) have been studied using native and (semi)synthetic LPs as both prolonged and targeted drug delivery systems. Since all reported loading methods are basically in vitro or ex vivo procedures with related limitations, an idea has been raised for finding a completely new loading paradigm to overcome the limitations in using native particles as drug vehicles. The basis for this hypothesis is that we are able to load native and circulating LPs without extracting them from body via using specific monoclonal antibodies (MAb, already linked to desired drugs or to be linked to drug via proper linker system such as avidin-biotin bridges) actively-targeted against specialized Apos available on the surface of all LPs. Obviously, by choosing the right anti-Apo antibody (preferably single chain variable fragment; scFv), we can select the right circulating LP subpopulation (i.e., LDL, HDL, VLDL, or CM). By considering all parameters and using the most appropriate strategy, this novel, safe, versatile, industrializable, and clinically translation-prone paradigm could be used for both prolonged and (LP receptor- and non-LP receptor-) targeted drug delivery purposes.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/84https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/84/84Journal of Medical Hypotheses and Ideas4Integration of Traditional Chinese Medicine and modern medicine promotes the unification of human medicine8585PengZhangLingQin20151005There are two mutually supportive systems in medical profession: modern medicines and traditional medicine. The current status is that although the modern medicine occupies the major position in healthcare system, the therapeutic effect of traditional medicines should not be omitted. If all of them merged and unified as one, it will be beneficial to the development of human medicine. In this paper, the integration of Traditional Chinese Medicine (TCM) and modern medicine was exemplified to elucidate the mutual complements, mutual benefits of traditional medicines and modern medicine to maintain the unification of human medicine via the development of molecular biology, cytology etc. We believed that TCM theory may share the same mechanism with western medicine at some extent which need to be explored in the future research. In our point of view, although the road may twist and turn, the results are promising.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/85https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/85/85Journal of Medical Hypotheses and Ideas4Hyponatremia, flux concentration and different species of malaria8686VirojWiwanitkit20151005Hyponatraemia is an important complication of malaria. The rate of hyponatremia is different in different kinds of malarial infection with a significant problem in falciparum malaria. The exact pathophysiology of hyponatraemia in malaria remains unclear. Here, the author proposes an idea on a parasitic sodium related biological process and further extrapolates for its relationship with rate and severity of hyponatremia in different kinds of malarial infection.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/86https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/86/86Journal of Medical Hypotheses and Ideas4Letter to the editor: Gold nanoparticle: bactericidal effect and safety?8787VirojWiwanitkit20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/87https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/87/87Journal of Medical Hypotheses and Ideas4Sedimentation rate in dengue: an explanation based on proposed hypothesis on weight and erythrocyte sedimentation8888VirojWiwanitkit20151005Dengue is an important mosquito borne viral infection. Focusing on the hematological finding in dengue, the erythrocyte sedimentation rate is varied. The exact explanation for this observation is unclear. Here, the author uses the previously already proposed hypothesis on weight and erythrocyte sedimentation for giving explanation of the observed sedimentation in dengue. This new explanation can fit with the already published observation in medical literature and indicates that erythrocyte sedimentation rate might be a useful predictor and classifier for kinds of dengue based on its severity.https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/88https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/88/88Journal of Medical Hypotheses and Ideas4Letter to the editor: Hyponatraemia, Plasmodium spp. and Na+/H+ exchange8989SimonBrown20151005https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/89https://ijmhi.tums.ac.ir/index.php/ijmhi/article/download/89/89