Journal of Medical Hypotheses and Ideas
Volume:8 Issue: 2, 2014

Although beta-amyloid (Aβ) has been regarded as the principal toxic factor in the pathogenesis of Alzheimer’s disease (AD), it plays important physiological roles in phenomena such as neuron survival, synaptic plasticity, and memory formation. There are numerous plausible reasons to assume that all of the mentioned pathological and physiological functions of Aβ may be partially mediated via alpha 7 nicotinic acetylcholine receptor (nAChR). Agonistic and antagonistic aspects of Aβ on nAChRs may explain this paradox in peptide–receptor function. It seems that Aβ shows antagonistic effects on α7 nAChR in a dose-dependent manner, and its pathologic function may partially correlate with antagonization of the receptor.If this hypothesis is supported, the related mechanisms of neurotoxicity, neuroprotection, memory formation, and AD pathogenesis might be identified. In addition, such knowledge helps make a more valid interpretation of neuron signaling and a better design of AD animal models. In addition, it may provide new insights into AD therapy development via reducing the amount of Aβ and inhibiting peptide aggregation.

Viral diseases such as influenza, which are easily transferable from person to person or even country to country, pose one of the biggest threats to health today. Viruses such as avian influenza viruses (N1H5 and H9N1) have been reported to spread in the present decade and, very recently, the novel coronavirus that has caused many life-threatening illnesses and deaths all around the world has received much attention.To prevent these highly contagious viral infections, we have proposed the combination of IMOD™ and Arbidol to increase their immunomodulatory effects as a novel medicine to prevent and cure influenza and some other infectious diseases such as hepatitis B and C. On the one hand, IMOD™ within the last few years has been proven to safely and effectively increase the life expectancy for human immunodeficiency virus (HIV)-infected individuals by increasing CD4 lymphocytes. On the other hand, Arbidol, an antiviral agent has been used safely and effectively in the past two decades to prevent and cure all types of influenza and flu. Therefore, the combination of both in a single dosage to further increase CD4 lymphocytes and interferon gamma (IFN-γ) could be a better choice for treatment of viral infections. This proposal tries to provide enough support and background for approval of a randomized clinical trial by a relevant team of investigators.

Cerebral arteriovenous malformations (AVMs) occur universally in 1. 1 per 100،000 people. These malformations are the cause of serious neurological morbidity or even death when they bleed. AVMs are not necessarily static congenital abnormalities. They can undergo internal changes due to angiogenesis resulting in vascular remodelling. They can even regrow after successful therapy. Vascular endothelial growth factors (VEGFs) play an important role in angiogenesis. Drugs that block the action of VEGF on vascular endothelial growth factor receptors (VEGFRs) on the endothelial cell surface are available. This blockade causes an anti-angiogenetic effect. Anti-angiogenic drugs are widely used as adjuvant therapy in the management of cancers because they suppress the formation of new blood vessels required by the tumour for growth. For similar reasons، they are used in the treatment of age-related macular degeneration. The present treatment options for AVMs are surgery، embolisation and irradiation either on their own or in combination. Irradiation with stereotactic radiosurgery (SRS) offers the advantage of being non-invasive، but it relies on the late radiation effects to achieve its therapeutic goal of complete obliteration. This latent time (1–3 years)، during which the risk for a bleed remains، is an inherent drawback of SRS. The histopathology of surgical specimens of post-SRS AVMs demonstrates a role of endothelial cells in repairing the radiation damage. Suppressing their activity post SRS by a VEGF blockade has the potential to enhance the radiation damage and hence speed up the obliteration process and reduce the latent time. It is postulated that such a ‘VEGF blockade’ could be useful as an adjuvant therapy to SRS. In addition، there is also the potential for a neo-adjuvant use، whereby a VEGF blockade could cause regression in the size of the AVM، making definite therapy easier. The rationale for the VEGF-blockade concept is presented and discussed.

The initiating event in multiple sclerosis (MS) pathogenesis is not known yet. However, in general, breakdown of the blood-brain barrier (BBB) and subsequent infiltration of immune cells into the central nervous system (CNS) has been thought to be the main initiating event. Nonetheless, the mechanism by which the BBB gets disrupted and allows immune cells to infiltrate into the CNS is not fully understood. Evidence indicates that prior to cellular infiltration, over passing peripherally generated cross-reactive immunoglobulin G (IgG) through the transiently permeable BBB during systemic inflammation, hypoxia, hyperthermia, transient hypertension or acute stresses may cause CNS inflammation, BBB breakdown and then initiation of MS disease. Here, we discuss the possible detailed mechanisms that may be involved in cross-reactive IgG-mediated MS autoimmunity.

Mandibular destruction resulting from tumours, trauma, congenital, ankylosis and other reasons leads to disturbed masticatory function. The ideal goal would be to reconstruct a condyle that is similar to the original. However, each of the condylar reconstruction approaches in current has specific shortcomings. Tissue engineering can provide a method to overcome these difficulties. A tissue-engineered mandibular condyle composed of bone and cartilage has been reported, but the strength and shape of the scaffolds used cannot meet the requirement of the clinical use. Freeze-dried allogenic condylar bone is biocompatible, bioresorbable of low antigenicity and provides the morphology for the condyle similar to the original. It is a good scaffold material for tissue engineering. The three-dimensional porous internal titanium scaffold is also biocompatible; it can be easily made into the shape that we need. The two scaffolds have sufficient mechanical strength before no bone formation. Hence, we hypothesise using a three-dimensional porous titanium scaffold or an allogenic bone scaffold combined with osteogenic, chondrogenic material and bone marrow stromal stem cells in vivo tissue engineering to repair condylar defects. This article discusses the hypotheses.

Science is a knowledge based on hypotheses, observations, and experiments. From its very beginning science has served the humanity and will continue to do so until the needs of human being are fulfilled. History is rich of many scientists who have contributed to different fields of science free of politics, religion, cast, and region. Every human being must have the right to use science and technology for beneficial purposes. Mutual coordination between academia and industries is extremely important for the growth of science. The spread of ideas is only possible with publication and distribution of information to all in the world. Unpublished new ideas will remain hidden. With no doubt, many of publications and products get the spirit from the very first ideas. It is necessary that all scientists share their ideas, opening new opportunities for others to work in the various aspects. We are of the view that, to find a solution to our problems or satisfy human needs, it is important to ponder new ways in science, generate new ideas and share with others, so the concept of “science for the benefits of all” remain alive forever.