Medical Hypotheses RSS feed: Current Issue. Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives. The Aims and Scope of Medical Hypotheses are no different now from what was proposed by the founder of the journal, the late Dr David Horrobin. In his introduction to the first issue of the Journal, he asks 'what sorts of papers will be published in Medical Hypotheses? and goes on to answer 'Medical Hypotheses will publish papers which describe theories, ideas which have a great deal of observational support and some hypotheses where experimental support is yet fragmentary'. (Horrobin DF, 1975 Ideas in Biomedical Science: Reasons for the foundation of Medical Hypotheses. Medical Hypotheses Volume 1, Issue 1, January-February 1975, Pages 1-2.). Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations. Submitted manuscripts will be reviewed by the Editor and external reviewers to ensure their scientific merit. All reviewers will be fully aware of the Aims and Scope of the Journal and will be judging the premise, originality and plausibility of the hypotheses submitted. Abstracting/indexing Medical Hypotheses is indexed and abstracted in: ADONIS, BIOSIS, Chemical Abstracts, Elsevier BIOBASE/Current Contents/Life Sciences, EMBASE Excerpta Medica, Index Medicus, Medical Documentation Service, Reference Update, Research Alert, Science Citation Index, SciSearch UMI (Microfilm), Russian Academy of Science http://www.medical-hypotheses.com/?rss=yesElsevier Inc.en © 2012 Elsevier Ltd. All rights reserved. Medical Hypotheses0306-9877783March 2012 © 2012 Elsevier Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.medical-hypotheses.com/article/PIIS0306987712000527/abstract?rss=yesTitle page/Editorial Board10.1016/S0306-9877(12)00052-7Medical Hypotheses 78, 3 (2012)2012-03-01Medical Hypotheses2012-03-01783S0306-9877(12)X0002-1iihttp://www.medical-hypotheses.com/article/PIIS0306987711006244/abstract?rss=yesAbstract: Radiotherapy (RT) has been established to improve both local control as well as overall survival rates in breast cancer. However, RT especially in left-sided breast cancer also irradiates a portion of the heart. Radiation associated toxicity to the heart assumes significance because of improval in survival of breast cancer patients. A circadian pattern has been reported in the myocardial oxygen demand and myocardial ischaemia with the cardiac tissue being more susceptible to injury between 6am and noon. Radiation damages blood vessels of all sizes causing an increase in capillary wall permeability and dilatation of vessels leading to the characteristic radiation erythema followed by an inflammatory cell infiltrate. Coronary artery spasm may be the reason behind some cases of sudden death occurring in patients after radiation therapy. Endothelial behaviour also has a circadian variation and vasodilation is significantly attenuated in the morning. Critical coronary artery disease occurs 10–15years after radiotherapy. Radiation in the morning hours may be one of the associated risk factor. The application of chrono-therapeutics with radiation therapy in carcinoma breast and in other chest wall irradiation, could possibly decrease the radiation associated cardiac toxicity.Cardioprotective radiotherapy: The circadian wayDeepak Gupta, Pragya Shukla, Anusheel Munshi, Jai Prakash Aggarwal10.1016/j.mehy.2011.12.009Medical Hypotheses 78, 3 (2012)2012-01-19Medical Hypotheses2012-01-19783S0306-9877(12)X0002-1Articles353355http://www.medical-hypotheses.com/article/PIIS0306987711006232/abstract?rss=yesAbstract: Keloids are benign tumours composed of fibrous tissue produced during excessive tissue repair triggered by minor injury, trauma or surgical incision. Although it is recognized that keloids have a propensity to form in the upper torso of the body, the predisposing factors responsible for this have not been investigated. It is crucial that the aetiopathoical factors implicated in keloid formation be established to provide guidelines for well-informed more successful treatment. We compared keloid-prone and keloid-protected skin, identified pertinent morphological differences and explored how inherent structural characteristics and intrinsic factors may promote keloid formation. It was determined that keloid prone areas were covered with high tension skin that had low stretch and a low elastic modulus when compared with skin in keloid protected areas where the skin was lax with a high elastic modulus and low pre-stress level. Factors contributing to elevated internal stress in keloid susceptible skin were the protrusion of hard connective tissue such as bony prominences or cartilage into the dermis of skin as well as inherent skin characteristics such as the bundled arrangement of collagen in the reticular dermis, the existent high tension, the low elastic modulus, low stretch ability, contractile forces exerted by wound healing fibroblastic cells and external forces.Stress promotes keloid formation by causing dermal distortion and compression which subsequently stimulate proliferation and enhanced protein synthesis in wound healing fibroblastic cells. The strain caused by stress also compresses and occludes microvessels causing ischaemic effects and reperfusion injury which stimulate growth when blood rich in growth factors returns to the tissue. The growth promoting effects of increased internal stress, primarily, and growth factors released by reperfusing blood, manifest in keloid formation. Other inherent skin characteristics promoting keloid growth during the late stages of wound healing in the upper torso are the thinner epidermis, the presence of vellus hairs, the absence of protective immunoglobulin A (IgA), and the thick fragile quality of upper torso skin. As it is not known why there is a predilection for keloids to form in the upper torso of the body, this hypothesis implicating and associating inherent morphological characteristics and elevated stress in the aetiopathogenesis of keloids is of potential value in terms of prevention, management and treatment of these enigmatic tumours.Involvement of upper torso stress amplification, tissue compression and distortion in the pathogenesis of keloidsShamin Bux, Anil Madaree10.1016/j.mehy.2011.12.008Medical Hypotheses 78, 3 (2012)2012-01-09Medical Hypotheses2012-01-09783S0306-9877(12)X0002-1Articles356363http://www.medical-hypotheses.com/article/PIIS0306987711006219/abstract?rss=yesAbstract: At the present time, the function of the mastoid remains unknown. One of the main hypotheses accredited in the literature interprets the mastoid as a pressure buffer. Other theories underline the role of the mastoid mucosa in pressure regulation by transmucosal gas exchanges. The question is what advantage does air reabsorption and the creation of a certain degree of negative pressure that mastoid seems to produce, bring to the middle ear and hearing? In the authors’ opinion, it is possible that the mastoid, or, in general, every kind of mucosa contained in the middle ear of mammals, would act to create a quite constant, although slight, negative pressure to obtain favorable compliance and impedance conditions in the middle ear to hear and transmit high frequency sounds and ultrasounds. The Eustachian tube, in this perspective, would compensate excessive values of negative pressure. Clearly, that function of mastoid pneumatization in humans would have lost its role, due to the absence of a sensorineural system to analyse ultrasounds.Mastoid: A vestigial function in humans?Matteo Alicandri-Ciufelli, Federico Maria Gioacchini, Daniele Marchioni, Elisabetta Genovese, Daniele Monzani, Livio Presutti10.1016/j.mehy.2011.12.006Medical Hypotheses 78, 3 (2012)2012-01-16Medical Hypotheses2012-01-16783S0306-9877(12)X0002-1Articles364366http://www.medical-hypotheses.com/article/PIIS0306987711006098/abstract?rss=yesAbstract: According to the core activity of calcium in the bone cellular expression, a new hypothesis linking calcium transport with the mechanical loading is proposed to explain the mechano-adaptation of bone tissue. Due to the piezoelectric coupling, the tensile and compressive areas of bone produce different electrical environments for the osteocytic cells that are embedded in the lacuno-canalicular porosity. This electrical asymmetry engenders a calcium enrichment–exclusion effect that strongly changes the calcium concentration in the lacuno-canalicular fluid and thus modifies the remodelling process. A bibliographic body of evidence supporting this idea is given and its experimental validation is suggested.Possible role of calcium permselectivity in bone adaptationThibault Lemaire, Salah Naili10.1016/j.mehy.2011.12.005Medical Hypotheses 78, 3 (2012)2012-01-05Medical Hypotheses2012-01-05783S0306-9877(12)X0002-1Articles367369http://www.medical-hypotheses.com/article/PIIS0306987711006086/abstract?rss=yesAbstract: Peri-implantitis can lead to bone destruction around a dental implant through inflammation and immune reactions caused by bacteria adhering to the surface of the implant abutment. Electromagnetic irradiation can inhibit bacterial growth, increase bone formation, decrease bone resorption and reduce the inflammatory response. Our hypothesis is that electromagnetic irradiation may be a new treatment approach for peri-implantitis and may simultaneously maintain bone mass around the dental implant. The results would be more significant when combined with other agents, because the effect of some antibiotics and anti-inflammatory drugs is strengthened by electromagnetic irradiation. This non-invasive therapy is expected to be conducted in a convenient manner, and even by patients at home, thereby facilitating the prevention and treatment of peri-implantitis.Electromagnetic irradiation may be a new approach to therapy for peri-implantitisZhensheng Cao, Yijia Chen, Yuxue Chen, Qing Zhao, Xiaomei Xu, Yangxi Chen10.1016/j.mehy.2011.12.004Medical Hypotheses 78, 3 (2012)2012-01-16Medical Hypotheses2012-01-16783S0306-9877(12)X0002-1Articles370372http://www.medical-hypotheses.com/article/PIIS0306987711006074/abstract?rss=yesAbstract: The mechanisms behind certain co-morbid conditions associated with chronic HIV disease still remain elusive. HIV-associated peripheral neuropathy is one among those rarely studied manifestations in HIV-1 infection. Numerous underlying factors associated with peripheral neuropathy have been described in HIV disease. Herein, we hypothesized certain heretofore undescribed potential mechanisms that lead to HIV associated neuropathy. Being a multifactoral manifestation, HIV-associated neuropathy is presumed to have an association with physiological factors namely, adrenal inadequacy/steroid resistance and lipodystrophy-induced cushion-effect loss in peripheral nerves. Therefore, management of the adrenals with steroids at the time-point of high inflammatory burden thereby preventing lipodystrophy by selecting the optimum treatment regimen could markedly alleviate the severity of HIV-associated neuropathic manifestations.Lipodystrophy and adrenal insufficiency: Potential mediators of peripheral neuropathy in HIV infection?Palanisamy Jayakumar, Esaki Muthu Shankar, Murugesan Karthikeyan, Pandian Ravikannan10.1016/j.mehy.2011.12.003Medical Hypotheses 78, 3 (2012)2012-01-16Medical Hypotheses2012-01-16783S0306-9877(12)X0002-1Articles373376http://www.medical-hypotheses.com/article/PIIS0306987711006062/abstract?rss=yesAbstract: Bisphosphonates are used in the oncological setting to treat and prevent skeletal-related events and preserve bone mineral density. Bisphosphonates also possess a hypocalcaemic effect. When undesired, hypocalcaemia can result in increased morbidity and complications. The currently understood mechanism of bisphosphonate-induced hypocalcaemia is by osteoclast inhibition. The effect of bisphosphonates on osteoblasts is less well understood. Laboratory studies demonstrate that bisphosphonates increase osteoblast and osteoblastic metastases maturation, activity and bone mineralization. We hypothesize that where large populations of osteoblasts exist increased mineralization may result in hypocalcaemia. Consequently patients with bone-metastatic prostate cancer may be more susceptible to symptomatic hypocalcaemia following bisphosphonate therapy. We are currently designing a study to investigate our hypothesis and to identify the risk factors of hypocalcaemia.Bisphosphonate stimulation of osteoblasts and osteoblastic metastasis as a mechanism of hypocalcaemiaJoon Wee Ho10.1016/j.mehy.2011.12.002Medical Hypotheses 78, 3 (2012)2011-12-29Medical Hypotheses2011-12-29783S0306-9877(12)X0002-1Articles377379http://www.medical-hypotheses.com/article/PIIS0306987711006050/abstract?rss=yesAbstract: Pituitary adenomas are common benign intracranial neoplasms representing about 10–25% of all intracranial neoplasm. Significant morbidity can occur along with pituitary adenomas due to hormonal dysfunction and mass effects. The pathogenesis of pituitary adenoma is unclear, however, etiologic factors include genetic events, hormonal stimulation, and growth factors , all of which promote cell proliferation and transformation in the tumor. However, genetic events play the most important role in tumorigenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, not only have function in pituitary cell proliferation and apoptosis but also in neoplastic transformation. It has been shown that miRNAs are differentially expressed in pituitary adenoma when compared with the normal pituitary gland; moreover, miRNAs have been identified as a predictive signature of pituitary adenoma and can be used to predict the histotype. The expression of miRNAs can be used not only to differentiate microadenomas from macroadenomas, but to also distinguish samples of treated patients from samples of non-treated patients. Therefore, we hypothesized that a miRNA-based network may be involved in pituitary tumorigenesis and it can potentially serve as useful diagnostic markers to improve the classification of pituitary adenomas. Here, we reviewed the therapeutic potential that different types of miRNAs may play in tumorigenesis. Moreover, miRNAs may emerge as potential therapeutic targets. We speculated the mechanism of miR-21 is involved in tumorigenesis, leading to improvements in therapies and prevention of metastasis.MicroRNAs-based network: A novel therapeutic agent in pituitary adenomaXiuhua Shi, Bangbao Tao, Hua He, Qingfang Sun, Changyan Fan, Liuguan Bian, Weiguo Zhao, Yi-cheng Lu10.1016/j.mehy.2011.12.001Medical Hypotheses 78, 3 (2012)2012-01-05Medical Hypotheses2012-01-05783S0306-9877(12)X0002-1Articles380384http://www.medical-hypotheses.com/article/PIIS0306987711006049/abstract?rss=yesAbstract: Dupuytren’s disease (DD) is a benign progressive fibro-proliferative disorder of the fascia palmaris of the hand. Currently, treatment consists of surgical excision with a relatively high recurrence rate and risk of complications. To improve long-term outcome of DD treatment, research focus has shifted towards molecular targets for DD as an alternative to surgery. Therefore, complete and exact understanding of the cause of DD is needed.Transforming growth factor (TGF)-β is considered a key player in DD. We recently showed that increased TGF-β expression in DD correlates not only with elevated expression and activation of downstream Smad effectors, but also with overactive ERK1/2 MAP kinase signaling. Both TGF-β/Smad and non-Smad signaling pathways increase expression of key fibrotic markers and contractility of Dupuytren’s myofibroblasts. What is not yet known is whether these two signaling cascades each accelerate DD autonomously, successively or in conjunction. Elucidation of this mechanism will help develop new potential non-surgical treatments.We hypothesize that TGF-β-induced short-term activation of the MAPK pathway leads to an autonomous non-Smad driven fibrosis. Therefore, successful treatment strategies will target not only TGF-β/Smad, but also intracellular MAPK signaling. In this review we discuss possible scenarios in which such a drift from TGF-β induced Smad signaling to autonomous non-Smad signaling could be observed in DD. The potential therapeutic effects of small cytokine signaling cascades inhibitors, such as TGF-β type I receptor-, (pan-) tyrosine- or ERK1/2 MAP-kinase inhibitor will be highlighted. To abrogate the fibrotic trait and the recurrence of DD, we speculate on sequential and co-application of such molecules in order to provide possible new non-operative strategies for DD.Concurrent inhibition of TGF-β and mitogen driven signaling cascades in Dupuytren’s disease – Non-surgical treatment strategies from a signaling point of viewC. Krause, P. Kloen10.1016/j.mehy.2011.11.023Medical Hypotheses 78, 3 (2012)2011-12-26Medical Hypotheses2011-12-26783S0306-9877(12)X0002-1Articles385388http://www.medical-hypotheses.com/article/PIIS0306987711006037/abstract?rss=yesAbstract: Tuberculosis is a human disease caused by infection with Mycobacterium tuberculosis. M. tuberculosis (Mtb) is a facultative intracellular pathogen. The alveolar macrophages provide a critical niche for the intracellular pathogen. It has been shown that virulent strains mycobacteria (Mtb-H37Rv, Mycobacterium bovis) induce less apoptosis in host macrophage than avirulent mycobacteria strains (Bacillus Calmette-Guérin, H37Ra). Comparative genomics analysis has revealed that the region of difference (RD1) of M. tuberculosis is absent from all strains of Bacillus Calmette-Guérin (BCG). On the contrary, it presents in all virulent strains of M. tuberculosis and M. bovis. The culture filtrate protein 10 (CFP10) and early secretory antigenic target protein 6 (ESAT6) are encoded by RD1 genes Rv3874 and Rv3875, respectively. Recent studies indicated that the CFP10 and ESAT6 played an important role in M. tuberculosis virulence. It has been shown that incorporation of the RD1 region into BCG to restore the expression of CFP10 and ESAT6 leads to increasing the virulence and immunogenicity of bacterium. On the contrary, deletion of the genes encoding CFP10 and ESAT6 from the virulent M. bovis strain results in attenuation of virulence. Meanwhile, several studies showed that CFP10 and ESAT6 could inhibit and/or promote the production of tumor necrosis factor α (TNF-α) from macrophages. Furthermore, TNF-α can induce apoptosis and necrosis of infected macrophages in tuberculosis. Considering above results, we hypothesize that the CFP10 and ESAT6 may be involved in the virulence of Mycobacterium through modulating macrophage cell death.The CFP10/ESAT6 complex of Mycobacterium tuberculosis may function as a regulator of macrophage cell death at different stages of tuberculosis infectionSi Guo, Rui Xue, Yi Li, Shan Mei Wang, Lin Ren, Jing Jing Xu10.1016/j.mehy.2011.11.022Medical Hypotheses 78, 3 (2012)2011-12-23Medical Hypotheses2011-12-23783S0306-9877(12)X0002-1Articles389392http://www.medical-hypotheses.com/article/PIIS0306987711006025/abstract?rss=yesAbstract: Insulin resistance is a hallmark of type 2 diabetes (T2D). The mechanisms underpinning β-cell mass expansion and their functionality in insulin-resistant states still remain elusive. It has recently been shown that insulin resistance in skeletal muscles leads to production of myokines that impact negatively on β-cell function. We hypothesize that multiple intramuscular injections (IM) of mesenchymal stromal cells (MSCs) at different sites would aid in countering the insulin resistance in T2D. These IM injections are expected to have dual effects in overcoming muscle insulin resistance. It is likely to modulate the micro environmental niche of insulin-insensitive myocytes under the influence of paracrine secretions from MSCs, in turn changing the myokine secretion pattern to positively regulate β-cell function. Further, it may stimulate the satellite cell population to generate new myocytes, which would be insulin-sensitive. If our hypothesis proves to be right, it might offer a user-friendly approach to control T2D.Can multiple intramuscular injections of mesenchymal stromal cells overcome insulin resistance offering an alternative mode of cell therapy for type 2 diabetes?Renjitha Gopurappilly, Ramesh Bhonde10.1016/j.mehy.2011.11.021Medical Hypotheses 78, 3 (2012)2011-12-22Medical Hypotheses2011-12-22783S0306-9877(12)X0002-1Articles393395http://www.medical-hypotheses.com/article/PIIS0306987711005925/abstract?rss=yesAbstract: Incidence of cardiovascular disease in patients with chronic autoimmune disorder like rheumatoid arthritis is much higher than in general population. Cardiovascular events (e.g. myocardial infarction or stroke) are caused by premature accelerated development of atherosclerosis. Chronic inflammation-enhanced atherosclerosis syndrome is proposed as a separate syndrome occurring in patients suffering of chronic inflammation. It is suggested that atherosclerosis as an inflammatory disease and long-lasting extravascular inflammation have common mechanisms resulting in an increase in atherosclerosis and its sequellae, cardiovascular diseases.Chronic inflammation-enhanced atherosclerosis: Can we consider it as a new clinical syndrome?Eugene Joseph Kucharz10.1016/j.mehy.2011.11.020Medical Hypotheses 78, 3 (2012)2011-12-19Medical Hypotheses2011-12-19783S0306-9877(12)X0002-1Articles396397http://www.medical-hypotheses.com/article/PIIS0306987711005913/abstract?rss=yesAbstract: Recently, there have been increasing evidences that microRNA-146 (miR-146) is related to up-regulated immune and inflammatory signaling through its target genes, such as IRAK1 and TRAF6. Additionally, abundant data continue to support the hypothesis that progressive up-regulation of inflammatory gene expression and elevated inflammatory signaling facilitate the development and progression of Alzheimer’s disease (AD). This review focuses on the recent findings regarding the role of miR-146 in modulating immune response and its subsequent effects in the pathogenesis of AD.The potential role of microRNA-146 in Alzheimer’s disease: Biomarker or therapeutic target?Li-Ling Wang, Yue Huang, Gang Wang, Sheng-Di Chen10.1016/j.mehy.2011.11.019Medical Hypotheses 78, 3 (2012)2012-01-03Medical Hypotheses2012-01-03783S0306-9877(12)X0002-1Articles398401http://www.medical-hypotheses.com/article/PIIS0306987711005901/abstract?rss=yesAbstract: Any classification is a step forward and it should help to determine the reason, the course, the prognosis, the treatment of a disease. The current classification of diabetes mellitus (DM) is really very convenient for work, but it has some drawbacks, and the absence of differentiation of type 2 diabetes is the main. The problem is the absence of an adequate criterion, based on pathogenesis for differentiation.We suppose that cell mediated immunity (CMI) to insulin plays the central role in the diabetes genesis. Autoimmune process may be triggered by viruses family Paramyxoviridae, in 10–20% of type 1 diabetes patients the disease is a consequence of direct cytotoxic effect of other viruses to the islet cells of pancreas. In acute phase of viral infection (measles, mumps, parainfluenza) CMI against viruses is developed, in some patients CMI to insulin appeared. We suppose that autoimmune reactions in these cases are the result of cross reaction between viral antigens and insulin. The majorities of patients suppress these reactions and recover from acute infection diseases with the antiviral immunity development and without any complications. Other patients are not able to suppress autoimmune reactions to insulin and pathological process is triggered. Type 1A diabetes is a result of direct CMI to insulin, and this process is responsible for beta-cells destruction; may be type 1B DM is due to the direct cytotoxic effect of other viruses or toxins to them.Some patients with acute viral infection cannot destroy the aggressive clone and they suppress autoimmune reaction to insulin by prostaglandin synthesizing cells (PGSC) or сells with histamine receptors (CHR). As a result of this process the insulin resistance is developed, because these cells or their cytokines form a block to the insulin receptors not only on immunocompetent cells, but in insulin sensitive tissues too.Patients with different reactions to insulin have different courses and outcomes of DM. We suppose that CMI to insulin is acceptable criterion for differentiation of DM, for identifying high risk group of patients in whom DM or its complications may develop. Moreover, prophylactic measures for decreasing of insulin resistance by nonsteroid anti-inflammatory drugs or histamine H2 receptor antagonists in persons with high activity of PGSC or CHR respectively can give good results.Furthermore, our hypothesis explains the initial reason for insulin resistance development, accordingly, it explains the reason for metabolic syndrome and atherosclerosis.Cell-mediated immunity to insulin: A new criterion for differentiation of diabetes mellitus?Nailya S. Asfandiyarova10.1016/j.mehy.2011.11.018Medical Hypotheses 78, 3 (2012)2011-12-19Medical Hypotheses2011-12-19783S0306-9877(12)X0002-1Articles402406http://www.medical-hypotheses.com/article/PIIS0306987711005895/abstract?rss=yesAbstract: Ovarian carcinoma is a significant cause of cancer mortality in women worldwide. As a heterogeneous disease, distinct clinical and molecular characteristics exist among different histologic subtypes. With the developments in proteomics, surfaced-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is sensitive enough to detect minute quantity of proteins from serum or microdissected cryostat sections. Herein we hypothesized that differentially expressed protein profiles exist in ovarian carcinomas with distinct histologic subtypes. Compared with endometrioid carcinoma, two peaks were significantly higher in serous carcinoma with the m/z of 3622Da and 4778Da, reinforcing the need to treat different histologic subtypes of ovarian cancer as different disease entities. Better understanding of these potential diagnostic and therapeutic biomarkers followed with proof-of-target effect will finally contribute to rational combinations of novel therapy and improve individual ovarian cancer patient outcome.Proteomic analysis reflects different histologic subtypes of epithelial ovarian cancerLin Jia, Hui Zhang, Xun Qu, Biping Deng, Beihua Kong10.1016/j.mehy.2011.11.017Medical Hypotheses 78, 3 (2012)2012-01-09Medical Hypotheses2012-01-09783S0306-9877(12)X0002-1Articles407409http://www.medical-hypotheses.com/article/PIIS0306987711005706/abstract?rss=yesAbstract: The serotonin transporter gene (SLC6A4) promoter polymorphism (5HTTLPR) has been associated with individual stress responses such that individuals with childhood abuse history have higher rates of depression in later life if they are homozygous short (s/s) of the gene. It is hypothesized that these findings could be explained by an integrated model of a role of the glial cell transporter and a functional difference of 5HTTLPR in the capacity of absorbing serotonin from the synapse.A hypothetical integrated model of the SLC6A4 function and the role of glial cells are put forward to explain accumulating results of recent investigations exploring the relationship between the gene and the diverse mental activities including depression and stress response.A model based on SLC6A4 variation is proposed to explain individual differences in stress vulnerability/resilience. The role of the glial cell transporter surrounding the synapse is integrated in the model to understand the modulation of the neurotransmission. It is hypothesized that a synapse with less serotonin transporter contributes to unstable processing in neurotransmission as compared to a synapse with more serotonin transporter. As such, based on functional differences of 5HTTLPR in the expression of the serotonin transporter, it is asserted that individuals with the s/s genotype process neurotransmission differently and in a reactive way.This integrated model of 5HTTLPR and glial cells suggests that the efficacy of serotonin reuptake in the synapse may play a crucial role in variability of neurotransmission, which can lead to differences in the stress response and the pathophysiology of depression.The integrated model of serotonin transporter gene variation (5HTTLPR) and the glial cell transporter in stress vulnerability and depressionGen Shinozaki10.1016/j.mehy.2011.10.043Medical Hypotheses 78, 3 (2012)2012-01-11Medical Hypotheses2012-01-11783S0306-9877(12)X0002-1Articles410414http://www.medical-hypotheses.com/article/PIIS0306987711006220/abstract?rss=yesSucralfate, which is used to treat gastric ulcers and other intestinal injuries , has a gastric cytoprotective effect due to its increase of mucosal defence mechanisms. It is minimally absorbed into the body, and it acts exclusive on the stomach and duodenum. Sucralfate is a locally acting substance, which reacts with hydrochloric acid in the stomach to form a cross-linked, viscous, paste-like material that can act as an acid buffer for up to six to eight hours. In addition, sucralfate prevents back diffusion of hydrogen ions, and adsorbs both pepsin and bile acids. Furthermore, sucralfate has been reported to stimulate the secretion of prostaglandin E2 and gastric mucus.Can sucralfate be effective to protect on peritoneal membrane in patients receiving peritoneal dialysis treatment?Erim Gulcan, Mustafa Keles, Abdullah Uyanik, Aynur Gulcan10.1016/j.mehy.2011.12.007Medical Hypotheses 78, 3 (2012)2012-01-09Medical Hypotheses2012-01-09783S0306-9877(12)X0002-1Correspondence415415