Journal of Medical Hypotheses and Ideas
Volume:4 Issue: 4, 2010

The 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.

Many 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.

Neovascularization 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.

The 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.

Neurodegenerative 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.

Amber 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.

The 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.