Journal of Medical Hypotheses and Ideas
Volume:3 Issue: 3, 2009

Thalassemia disorder is an important congenital red blood cell disorder. For laboratory screening, fragility is a useful test. The reduction of fragility test of red blood cell in thalassemia was noted, however, there is no report focusing on the physical force change occurring in this test. An idea focusing on the osmotic fragility of red blood cell in thalassemia is hereby proposed. Reduction of force at cell surface can be observed explaining the observation on resistance to fragility test of red blood cell in thalassemia.

Both cardiac structure and hand proportion have been linked with the Fibonacci Series and the associated Golden Ratio - the number 1.618 that has been postulated to be related to functional optimization. In this paper, evidence supporting the relation of the Golden Ratio to the hand and heart is presented. It is known that upper limb malformations are the commonest skeletal abnormalities in patients with congenital heart disease. Embryological studies on hand-heart syndromes have provided evidence for a cardiomelic developmental field, which is supported by candidate genes involved in patterning of the hand and heart. Precise molecular interactions govern a certain optimal model of cardiomelic development, for which the underlying physical rule remains unknown. It is hypothesized that the Golden Ratio may represent the mathematical basis for hand-heart development so as to achieve optimal form and function. Deregulation of this underlying patterning law may manifest as variation in hand-heart structure away from that as would be determined by the Golden Ratio. Altered hand proportion in turn may be of predictive value for cardiovascular defects and dysfunction.

The target of malarial parasite in infection process is erythrocyte. The pathology of red blood cell in malaria is of interest. Here, the author proposes an idea that malarial parasite can lead to increased erythrocyte volume and has significant effect on erythrocyte fragility.

Nasolacrimal There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Ideally, increasing knowledge of the mechanisms of atherosclerotic plaque destabilization should be translated in clinical practice. Systemic approaches are pursued to discover serum biomarkers that are applicable to define patients at risk for future cardiovascular events. Elevation in inflammatory markers, such as C-reactive protein, predicts outcomes of patients with acute coronary syndromes. Osteoprotegerin (OPG) protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL) and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. Emerging evidence from in vitro studies, mouse genetics and clinical studies attributed to OPG an important role in vascular biology. But conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD). Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process; we hypothesized that RANKL:OPG ratio could be a better biomarker for CAD.

The target of malarial parasite in infection process is erythrocyte. The pathology of red blood cell in malaria is of interest. Here, the author proposes an idea that malarial parasite can lead to increased erythrocyte volume and has significant effect on erythrocyte fragility.

Curcumin (diferuloylmethane) is an active component of the spice turmeric and has been linked with anti-inflammatory and chemopreventive activities. The present hypothesis explained the involvement of anti-inflammatory effects of crcumin in prevention of acute coronary syndromes (ACS) (i.e. unstable angina and myocardial infarction). ACS is the leading cause of death in both developed and developing countries. Coronary events often result from thrombi that form because of physical disruption of the atherosclerotic plaque. However, despite lipid lowing therapy with statins, significant numbers of cardiovascular events continue to occur indicating the need for additional agents for atherosclerosis management. We proposed that curcumin therapy can stabilize vulnerable 'rupture-prone' plaques by normalizing plaque properties. Thus, co-administration of curcumin along with other present options may prove to be a useful and potent natural plaque stabilizing approach in the prevention of ACS.

Venom immunotherapy (VIT) protects patients with hymenoptera venom anaphylaxis from subsequent potentially life-threatening reactions. The most important side effects during VIT are systemic anaphylactic reactions (SAR), which are more prevalent during honeybee VIT. Despite the demonstrated diversity with regard to venom compounds, previous publications did not mention the plausible reason that can justify the difference of SAR frequency between honeybee and wasps. On the other hand, pre-treatment with H1-blocking antihistamines reduces the frequency and intensity of local and mild systemic anaphylactic reactions during VIT, but not appropriately moderate adverse reactions such as abdominal pain or angioedematous reactions, which can occur more prevalently also during honeybee VIT. In contrast to hymenoptera venom (HV) anaphylaxis, these symptoms are very common during hereditary angioedema (HAE). In addition, in some patients who repeatedly experienced anaphylactic reactions during hyposensitization with HV are reported significantly lower renin, angiotensinogen I, and angiotensinogen II plasma levels. These facts may indicate that during honeybee VIT could be occurred a defective implication of renin-angiotensin system. This may be possible, because among hymenoptera, only the HV contains the antigen melittin, a potent kallikrein activator. These effects during honeybee VIT are similar to the HAE, because melittin-induced kallikrein activation on the first hand, as well as the implication of complement classical pathway during HAE on the second one, can lead both to increased bradykinin (BK) secretion, plasma extravasation, and therefore to the occurrence of angioedema and abdominal symptoms. Consequently, the clinical effectiveness of BK receptor and generator blockers such as icatibant, ecallantide or NPC 18884, shown recently during the treatment of HAE attacks and acetic acid-induced abdominal constrictions in mice, may lead to the hypothesis that a similar strategy could be useful during honeybee VIT in order to manage or prevent BK-induced symptoms such as angioedema and abdominal pain. However, the evaluation of this idea needs further appropriate experimental and clinical trials.

Lumbar interbody fusion techniques are becoming more and more minimally invasive. AxiaLIF technique can be used in low back pain caused by degenerative disc disease or minor spondylolisthesis, but there are risks for fusion failure. Intravertebral bone graft is performed in painful osteoporotic or posttraumatic vertebral compression fractures (VCFs). Until now, no attempt has been made to apply intravertebral bone graft with AxiaLIF technique.So first, we hypothesize a novel method for tridimensional intravertebral bone graft with a special designed bone grafting instrument and describe it vividly. The special instrument would mainly consist of a hollow tube and a rod, the distal parts of them would be shape into 45o slope, so the direction of grafting would be decided by the slope. By rotating the tube we can deliver cancellous bone granules in one plane, but by retreating the tube we can perform tridimensional intravertebral bone graft. Second, intravertebral bone graft is supposed to be performed combined with AxiaLIF technique in order to create biologic vertebral reconstruction and raise fusion rate. We believe this is the first description of such a method, future clinical studies are needed to validate these hypotheses.

Carious primary teeth are still a great problem in many countries. Maintaining these teeth, which play a significant role in chewing, guiding the permanent teeth to erupt normally and keeping the ideal dental arch size, is very important. The most common treatment of the deep carious primary teeth is pulpotomy. Many techniques and sub-base materials have been suggested for this purpose.All traditional sub-base materials have been found to have different percentages of failure. Bonding systems are widely used in dentistry for tooth restoration. Their greatest advantage is providing better seal in the tooth-restoration interface, which is the primary goal in restorative dentistry. The author's suggestion is to use these materials as a sub-base agent subsequent to the electrosurgical pulpotomy technique. Bonding systems are easy to use, time efficient, biocompatible, do not need sealing pressure, and additionally provide an ideal seal.

Anemia is one of the most common hematological disorders that are still the present in all countries around the world. Microcytic anemia is a specific kind of anemia presenting with small red blood cell. In this paper, the author discusses on the estimated red blood cell thickness, a new proposed parameter, comparing between that of iron deficiency anemia and thalassemia and further extrapolate on the clinical implication.

Nanoscience and Nanotechnology has enabled us to produce new atomic, molecular and cluster structures with desired properties in systematic and controlled approaches. Nanoelectronics (or Molecular Electronics) circuits which is based on molecular and quantum mechanical concepts and phenomena, can be used to design an intelligent system for the detection and prognosis of the initial electrical signals of the nervous and epileptic seizures. The design of the required power source based on the electrical currents of the nervous system and the location of the installation site are the most important features of the design and application of such an intelligent system. In the design of the molecular components needed for the nanoelectronic circuits of this system, physcochemical theoretical and computational techniques can be used. For the optimal design and performance of this prognosis system, environmental effects such as local electric and magnetic fields, and biochemical environments, should be taken into account.In this article, the idea of the design of an intelligent nanoelectronic system for the detection, prognosis and possible control of epileptic attacks is presented. The phases of the design, application and performance analysis of this system include; 1) Detailed clinical analysis of the epileptic electrical signals prior, during and after the attack. 2) Feasibility study of the simulation of the nervous system and the perturbative effects of the epileptic seizure on it using in vivo nanoprobes. 3) Feasibility study of the usage of electric signals of the nerves of other organs having less complexity compared to brain for faster and more accurate prognosis. 4) Design of an in vivo nanoelectronic circuit for the detection and prognosis of the initial signals of epileptic seizures. 5) Feasibility study of the design and production of nanoelectrodes implantable in the skull for the reduction or extinction of the perturbative nervous signals in order to minimize the effects of epileptic seizure.

Targeted delivery of drugs and proteins to liver can be achieved via asialoglycoprotein receptor, which can recognize and combine the galactose- and N-acetygalatosamine-terminated glycoproteins. Glycosyl is usually conjugated with drugs directly to fabricate prodrugs or with nanoparticles encapsulated drugs via forming covalent bonds, while the covalent bonds may lead to some shortages for drug release. Therefore, we have a hypothesis that we can prepare nanoparticles for efficient targeting by glycosylation using galactosylated poly (L-glutamic acid) (Gal-PLGA) as a carrier to entrap the model drugs in nanoparticles core physically rather than forming covalent drug conjugation. The means of incorporation of drug in nanoparticles may improve drug release to maintain its activity, raise its therapeutic index and diminish the adverse effect. Based on previous researches, it is achievable to obtain nanoparticles that we hypothesize to prepare. Due to their nanometer-size and galactosyl, the nanoparticles may be a potential delivery system for passive and active targeting to liver parenchymal cells for therapy of hepatitis and liver cancer.

The target of malarial parasite in infection process is erythrocyte. The pathology of red blood cell in malaria is of interest. Here, the author proposes an idea that malarial parasite can lead to increased erythrocyte volume and has significant effect on erythrocyte fragility.

Dissertation is the last part of student's study carried out under supervision of academic staff. Graduate theses are important sources of academic research; its results should go to science and industry. Here regarding to experiences up to now, an idea is proposed to oblige teaching of "Research Methodology" as course for Pharmacy students. Although "Research Methodology" has been launched in some universities as a workshop but the problem is just a few energetic students attend in, whereas for all doctorate students training is not over before defence of a thesis; and, because of the short time of this workshop (2-3 days) its outcome is not enough efficient.Attempts have been made to evaluate all registered theses (n=474) in library of faculty of Pharmacy, Kerman University of Medical Sciences in 20 years considering to their quality and quantity. The results showed that no statistic was used in 85% of theses. The structure of theses was not harmonized and the weakest parts of theses were analysis, discussion/conclusion. The most frequency of Pharmacy theses were in Pharmaceutics field. One out of six theses have been published in scientific journals; therefore regarding to our results and even other studies on medial theses in Iran, it seems necessarily to teach students how communicate, think, research, analyze and write scientifically and effectively to present their dissertations or articles in a professional way which should be covered by "Research Methodology" course.

Annually, multiple research projects are implemented in medical universities, but their results are not efficiently utilized. This condition has resulted in an increased focus on promoting the status of research-based knowledge transfer in the university. It was in response to this need that certain studies were conducted to determine the interventions required for efficiently utilizing research-based knowledge. The results of these studies were multiple measures and interventions that can collectively promote the status of research-based knowledge translation.Some of these interventions were as follows: designing an algorithm for selection of research projects which are legible for knowledge transfer, compiling a code of ethics for observing research stakeholder's intellectual property rights, modifying faculty member's promotion criteria to create incentives for knowledge transfer, modifications in presentation of articles, modifying proposal and final report formats, and designing a backing database. The impact of each hypothesis (intervention) will be evaluated through a study appropriate to it's content. The results of this study can be beneficial to research policy makers to utilizing research-based knowledge efficiently.

What is medical journals purpose of publishing research? These objectives have significantly changed since the first medical journals have been published; accordingly article formats have also transformed. Initially publication of articles was done with the purpose of informing the other researchers, but gradually, as the volumes of information and research target audiences increased, certain changes such as formatting abstracts and full texts were implemented in article presentations to inform target audiences in the shortest time. The question now is, how have medical journals moved on following the occurrence and development of evidence-based medicine and subsequently knowledge translation which highlight the importance of changing target audience's behavior on the grounds of new evidence?In order to identify the changes introduced in journals to promote knowledge translation, a search was conducted in electronic journals that were accessible. Eventually, it was observed that two important events had taken place in medical journals: changing article formats and creating new journals. In some journals there is a separate section that clearly highlights the essence of the study. For example inserting questions like "what does your study add to the current knowledge available?" or "how can the results of this study change target audience's behavior?". On the other hand, journals were created that only publish systematic review studies.Unfortunately, the aforementioned changes have not been addressed by many international and domestic medical journals. Therefore, in order to strengthen knowledge translation through journals in the country, we suggest inserting a section titled "Overview Box" in addition to formatting abstracts. To assess the impact of this intervention in improving the status of knowledge translation, we suggest an interventional study aimed at examining the impact of this box and properly transferring the article's messages and its impact on service provider's clinical practice. We expect to see enhancement of knowledge translation through this intervention, and to bring research knowledge closer to its rightful utilization.

Cyclosporine A (CsA) is a powerful immunosuppressant drug most widely used in management of organ transplantation and autoimmune diseases. However, in therapeutic doses CsA induces several side effects including renal and liver toxicity. CsA induced hepatotoxicity usually occurs in the first 90 post-transplant days and can limit its therapeutic use. Cumulative data showed that oxidative stress induced by reactive oxygen species (ROS) over production and compromised antioxidant capacity play an important role in the development of hepatotoxicity in CsA treated patients. CsA induced oxidative stress decreases hepatocyte reduced glutathione (GSH) and impairs the function of its related enzymes. Consequently any mechanism which removes ROS or prevents hepatic GSH depletion or induce production of GSH dependent enzymes may provide protection for hepatotoxicity in CsA-treated patient. Garlic organosulfur compounds have been reported that enhance cellular antioxidant activity by radical scavenging abilities and augmentation of endogenous antioxidants via prevention of GSH depletion and increasing of GSH dependent enzymes activity and their gene expression. Based on these facts we propose the hypothesis that garlic organosulfur compounds can prevent CsA hepatotoxicity. Before clinical use further investigations in animal models are needed.

Research-based knowledge transfer is considered an important principle in health. The status of knowledge transfer was studied in earlier studies and accordingly certain interventions were designed on the basis of its weaknesses. The idea was to design an algorithm for selection of research projects which are legible for knowledge transfer.Using literature review, grading of research projects was examined for its design and methodology. A decision was then made on the method of grading projects using relevant expert opinions. In the next stage, considering the validity of the aforementioned grading, and contextual examination, an algorithm was designed to define the method of selecting projects and their result transfer.Since articles usually dont convey all the research findings, and dont reach decision makers on time, article writing doesnt seem sufficient for knowledge transfer. It is therefore necessary to adopt a mechanism that will convey valid research findings to target audiences. The algorithm presented in this article will help research authorities systematically decide about selecting research projects for knowledge transfer. Evaluation of this intervention was suggested for future researches. The results of this study can be beneficial to research policy makers in the university.

One of the vital aspects of transferring research results is intellectual property of information. The key point in intellectual property is lack of use or misuse of research results. At times the urgent or early transfer of research results is necessary, and at times it is not possible prior to peer review. Since there were no specific rules in this field in the country, one of the innovations suggested for strengthening knowledge translation was compilation of an ethical code for research to promote knowledge translation by safekeeping stakeholder's intellectual property rights.The current status of knowledge translation in the university has been evaluated by the research team. Among the most important issues of disseminating research results prior to publication is the prerequisite of peer review. Dissemination of research results is also dependant on the contract made on intellectual property rights, the type of data, and the urgency of their early publication. The final draft is a figure that has been illustrated in the full text. After compilation and implementation of the ethical code in the country's research system, in addition to re-evaluating the knowledge translation status of the university, the role of this specific innovation should also be assessed in bringing about any change in this status.In Iran the medical universities provide resources for research. We therefore suggest two recommendations under the current circumstances: to promulgate the use of the mentioned ethical code, and to add a clause to the university's research contracts in which the university will have the right to disseminate research results in the target audience's language if they are beneficial to the community and scientifically valid.

In today's world the importance of research has reached a stage where, in academic settings the rate of presenting research articles is considered as a merit in scientific evaluations. The numbers of research articles published in internationally acclaimed databanks are also taken into account and scored in academic promotion criteria. This is indicative of the progress research has made in the country. The important point is that once a project is over the only way the results reach target audiences is through publication of articles, and proper measures are not taken to transfer the research results to their respective target audiences and apply them (knowledge translation). Therefore the studies conducted are not applied in meeting the country's research needs, community's health and decision makings at macro level. It is now time to encourage researchers toward utilization of research by considering research-based knowledge translation activities in the faculty member's promotion criteria. In this study we examined the promotion criteria of renowned universities in the world for the presence of knowledge translation activities and compared them with our own criteria. The result is the suggestion of allocating scores to studies conducted at various levels (organizational units of the university or its equivalent, the university or national level) that result in change in service delivery, management techniques, and/or lifestyles.

To date, there have been no curative drugs for inflammatory bowel disease (IBD). Conventional drugs and biologic agents are not always effective and may cause serious side effects. Therefore, it is still challenging to develop effective and safe novel drugs for IBD. Although the exact etiology of IBD remains elusive, it is generally accepted that the immune system of the gut plays a central role in the pathogenesis of IBD. Recently, the nuclear transcription factor kappa B (NF-κB) has been identified as the pivotal elements in the regulation of the increased inflammatory activity. Moreover, recent studies have shown that Cordyceps pruinosa extract is a inhibitor of NF- κB activation and can enhance weak immune functions. Based on these facts, I hypothesize that Cordyceps pruinosa extract may thus exert its therapeutic effect on IBD by regulating NF-κB activity and improving impaired immune functions.

The use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a hopeful idea for skeletal muscle repair. Autologous stem cells derived from muscle and bone marrow stem cells offers hope for the treatment of intractable muscle degenerative disorders; however, because the stem cell population is very small and decrease of mesenchymal stem cells (MSCs) in bone marrow with increased age, the problem of inadequate tissue supply for therapeutic scale arises. We hypothesized that endometrial stromal cells are more suitable candidate for muscle regeneration.

Cisplatin, a simple inorganic compound, has been one of the leading antitumor drugs especially for solid tumors for near 30 years. The mechanisms of cisplatin include denaturation of DNA and cell mitochondria, arresting cell cycle in the G2 phase and eventually causing apoptosis, inflammation, necrosis and death in cells. Apoptosis is a process of programmed cell death through cystein proteases named ‘caspases'. Pathways of caspase-mediated apoptosis can classified as ‘mitochondrial' pathway and ‘death receptor' pathway Especially caspase-3 plays a crucial role in cisplatin-induced nephrotoxicity through the pathways of apoptosis. The mammalian target of rapamycin (mTOR), is a serine/threonine kinase that regulates both cell growth and cell cycle progression through the phosphotidyl 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. mTOR regulates both cell growth, cell cycle progression and angiogenesis. By targeting mTOR, the immunsuppressant and antiproliferative agent Rapamycin inhibits signals required for cell cycle progression, cell growth, cell proliferation and angiogenesis. Angiogenesis is extremely important in tumor progression and metastasis. Although rapamycin is proapoptotic agent especially in cancers, there is an evidence that rapamycin can also have antiapoptotic properties through pleiotropic function in the regulation of cell death depending on the cell type and activation state as well as downstream targets of antiapoptotic molecules such as p53 and Bcl-2 proteins. Activation of caspase signaling pathways and dysregulation of pro- and antiapoptotic Bcl-2 proteins have been described previously. So there are links between the mTOR and caspase signaling pathways. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity such as acute tubuler necrosis (ATN) causing acute renal failure (ARF). Several agents have been tested to see whether they could ameliorate or augment the nephrotoxicity of cisplatin. Therefore, we hypothesize that mTOR inhibitor rapamycin can inhibit cisplatin induced ATN and ARF through the mechanisms including PI3K/Akt signaling and mitochondrial cell death pathway by affecting apoptosis. If this hypothesis will be proved by experimental and clinical studies, the patients with solid tumors receiving cisplatin may also be treated with mTOR inhibitors to reduce cisplatin induced nephrotoxicity.