Journal of Medical Hypotheses and Ideas最新文献

Insulin-dependent diabetes mellitus (IDDM) is considered to be a consequence of unchecked auto-immune processes. Alterations in immune system responses are thought to be the cause of the disease, but the possibility that altered metabolite levels (glucose) can establish the disease by specifically acting on and altering thymus stroma functions has not been investigated. Therefore, the direct effect of hyperglycaemia (HG) on central tolerance mechanisms as a causative agent needs to be investigated.

It is sometimes asserted, as a matter of dogma, that a local treatment cannot have systemic effects. However, treatment with radiotherapy directly localised on a tumour can profoundly affect tumour cells in the other tissues far from the radiated part. In 1953, Dr. Mole called this surprising phenomenon the ‘abscopal effect’. Since its discovery, very little is known about the exact mechanism and the key mediators of this astonishing phenomenon and many other questions in this context still remain unanswered. An understanding of this phenomenon could help to control the fatal face of cancer which is metastasis, and this discovery in turn will introduce promising strategies for treatment of advanced and not-curable cancers. Based on current information, we propose that there is a particular molecule(s) or macromolecule(s) that mediate(s) the abscopal effect. We also speculate that the frequency of the abscopal effect varies between different tumour types and the newly discovered molecule(s) or macromolecule(s) can enhance/instigate the abscopal effect in those tumour types that show a low frequency of the abscopal effect.

Despite the current existence and availability of synthetic drugs for the treatment of diabetes mellitus (DM), these medications are neither cheap nor completely effective. Furthermore, the long-term consumption of synthetic drugs may cause adverse effects, while those medications provided from natural sources are more affordable and have shown lesser adverse effects. The current belief is that oxidative stress plays a substantial role in the pathogenesis of diabetes and its complications. The characteristics of DM as a multifactorial disease are related to a deficit in the β-cells of the pancreas that results in defective production and release of insulin. Antioxidant therapy can protect β-cells from apoptosis and preserve their function. Therefore, the higher the antioxidant effects a compound might have, the higher the positive effects in diabetes anticipated. Our idea is that a combination of strong antioxidants might positively work in control of hyperglycemia by activating the production and release of insulin to the blood. In this scenario, if the strongest multi-herbal antioxidant complex called Setarud (IMOD™) is combined with curcumin and quercetin, then much stronger antioxidant activity with positive effects in the control of diabetes would be produced. To prove the idea, this combination has to be pharmaceutically prepared and then its safety and efficacy must be examined in preclinical and clinical studies.

In medicine, the relationship between erythropoietin and heart disease is sometimes mentioned. An attempt to demonstrate connection between erythropoietin and heart failure is very interesting. The attempt is based on the interrelationship among erythropoietin disturbance, anemia and heart disorder. However, the factors that can affect the endemic pattern must be considered.

Curcumin is a functional food, which provides a wide range of health benefits including anti-cancer activity and considered as a suitable alternative for chemotherapeutic agents. However, cancer cells exhibit resistance to most chemotherapeutic agents including curcumin due to overexpression of adenosine triphosphate (ATP)-binding cassette transporter proteins in the cancer cell membrane, which decrease the intracellular concentration of chemotherapeutic agents. Similarly, most chemotherapeutic agents including curcumin experience lack of cancer cell targeting, lack of aqueous solubility, rapid systemic clearance, intestinal metabolism and hepatic metabolism. These limitations hinder the clinical usefulness of curcumin in the treatment of multidrug-resistant cancers. In this article, we propose curcumin–piperine, or curcumin–quercetin or curcumin–silibinin dual drug-loaded nanoparticulate combination therapy to target and treat multidrug-resistant cancers. The proposed dual drug-loaded nanoparticulate combination is expected to reverse the multidrug resistance, prevent the rapid systemic clearance, prevent the intestinal and the hepatic metabolism, increase the aqueous solubility, enhance the bioavailability, target the cancer cells, produce a synergistic anti-cancer effect and enhance the efficacy of curcumin in the treatment of multidrug-resistant cancers.

The immune system is reported to be highly sensitive to different stressors that exist during space flight. Immune system dysregulation during and immediately following space missions is extensively reported. Solar and galactic radiation are among the major environmental factors which increase the risk of infection during extended stays of humans outside the Earth’s magnetic field. It has been reported that in addition to the effects on the host immune system, decreased antibiotic potency and enhanced microbial virulence are outcomes of long-term space flights. In long-time space missions, the probability of transformation of the neutral microorganisms into the harmful ones can pose a threat to astronauts’ health. In a widely cited publication, we suggested that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We hypothesised that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility of the selected astronauts and better protect astronauts against the unpredictable exposure to solar flares and coronal mass ejections. On the other hand, the results obtained in our recent studies indicate that exposure of laboratory animals to radiofrequency radiations emitted from a common mobile phone can induce a survival adaptive response as increased survival rate at a specific time after exposure to a pathogenic micro-organism. We recently indicated that pre-exposure of mice to radiofrequency radiations emitted from a GSM mobile phone (GSM, global system for mobile communications) increased their resistance to a subsequent Escherichia coli infection. The survival rates in 25 animals that received both adapting (radiofrequency) and challenge doses (bacteria) and the 20 animals that received only the challenge dose (bacteria) were 56% and 20%, respectively. In this light, our findings lead us to assume that this phenomenon can be used as a method for decreasing the risk of infection during deep space missions.

Aluminium phosphide (AlP) is a storage fumigant pesticide, which is used to protect stored grains especially from insects and rodents. It releases phosphine (PH₃) gas, a highly toxic mitochondrial poison, in contact with moisture, particularly if acidic. Although the exact mechanism of action is unknown so far, the major mechanism of PH₃ toxicity seems to be the inhibition of cytochrome-c oxidase and oxidative phosphorylation which eventually results in adenosine triphosphate (ATP) depletion and cell death. Death due to AlP poisoning seems to be as a result of myocardial damage. No efficient antidote has been found for AlP poisoning so far, and unfortunately, most of the poisoned human cases die. PH₃, like ammonia (NH₃), is a Lewis base with a lone-pair electron. However, boric acid (B(OH)₃) is a Lewis acid with an empty p orbital. It is predicted that lone-pair electron from PH₃ is shared with the empty p orbital from B(OH)₃ and a compound forms in which boron attains its octet. In other words, PH₃ is trapped and neutralised by B(OH)₃. The resulting polar reaction product seems to be excretable by the body due to hydrogen bonding with water molecules. The present article proposes boric acid as a non-toxic and efficient trapping agent and an antidote for PH₃ poisoning by investigating the chemical reaction between them.

The screening method for congenital thrombopathies using an impedance haematology cell counter is a challenging proposal. However, there are two important concerns, the difference of analytical properties among different kinds of analysers and the use of a specific anticoagulant in the platelet parameter study.

Glanzmann thrombasthenia (GT) and Bernard–Soulier syndrome (BSS) are hereditary autosomal recessive disorders of platelet functions. These two congenital thrombopathies are very rare. This rarity might be due to the misdiagnosis of the disease and the lack of reliable screening methods. Usually, the definitive diagnosis of these congenital defects relies on aggregometric, flow cytometric and molecular assays. Unfortunately, these expensive diagnostic tools are not always available in routine laboratories, especially in developing countries, leading to misdiagnosis and underestimation of the prevalence of these defects. In this paper, the authors suggest a simple and accessible screening method for detection of congenital thrombopathies using only a haematology counter and some reagents.