Abstract：
:Drug biotransformations are controlled in the body by tissue-differentiated choice of a selection of the induced and constitutive 57 isoforms of the human cytochromes P450 (CYP). CYP are the mixed function oxidase enzyme family (EC 1.14.14.1: mono-oxygenases that contain iron-dependent protohaematin IX). Many of the major side effects of clinical therapeutical agents have been attributed to the generation of highly toxic "reactive oxygen species" (ROS). Such ROS generation can be circumvented however by the ability to exert control over which forms of CYP are present: and as to which are bioactive in tissues other than the drug-target ones. Up to 57 isoenzymes of human cytochromes P450 are likely to be present: generation of a variety of species of ROS can be anticipated therefore with outcomes that include cancer, premature ageing, heart (arterial) damage and osteoporosis (in association with oestrogen/testosterone imbalance). Moreover, therapeutic vaccines could be constructed to remove the most harmful forms of cytochromes P450. Designer CYP protein enzymes can now be readily constructed by genetic engineering techniques: these include site-directed mutagenesis to place the modified cyp gene in suitable enzyme expression location in particular tissues only. Furthermore, gene therapy could be arranged to augment (or replace activities lost) for example the production of insulin in the Islets of Langerhans of the pancreas by production of the appropriate form of human insulin in the liver.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Wiseman Adoi
10.1016/j.mehy.2004.10.010keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
802-5issue
4eissn
0306-9877issn
1532-2777pii
S0306-9877(04)00575-4journal_volume
64pub_type
杂志文章abstract：:Alcoholism is a major and world-wide health problem. A characteristic pattern of congenital defects, known as the fetal alcohol syndrome, has been detected in the offspring of mothers who are chronic alcoholics. The mechanism underlying the teratogenic effects of ethanol is not known. An important hypothesis is that e...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90185-2
更新日期：1991-02-01 00:00:00
abstract：:The disturbances of the 11p15.5 chromosomal region are associated with Beckwith-Wiedemann syndrome, Russell-Silver syndrome, Wilms tumor, IMAGe syndrome, and idiopathic hemihyperplasia. The aim of this research was to examine the hypothesis that 11p15.5 initially became unstable in the European population about 200 ye...
journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
doi：10.1016/j.mehy.2018.09.008
更新日期：2018-12-01 00:00:00
abstract：:It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells. Should this be true, then treatment with a calcium antagonist (CA) may possibly be of value. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(94)90049-3
更新日期：1994-07-01 00:00:00
abstract：:Nearly two million people suffer traumatic brain injury in the US each year. These injuries alter adversely the metabolism of myelin, a major lipid material in brain, both in people and in experimental injuries of animals. A newly discovered and severe human neuropathy from copper deficiency provides evidence that som...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.09.011
更新日期：2013-12-01 00:00:00
abstract：:Mandibular asymmetry (MA) is one of the most common craniofacial malformations. However, there is no optimal technique for this malformation nowadays. A novel technique for both children and adults with less disadvantages is a must. Parathyroid hormone (PTH) is a straight-chain polypeptide secreted by the parathyroid ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.10.047
更新日期：2010-04-01 00:00:00
abstract：:Viral infections are often the etiological agents of severe acute and chronic human diseases. Their peculiar biology usually leads to the need of design specific therapies for each virus, and the eradication of the viruses and the healing of the patients very often are not reached also after decades of theoretical and...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.06.004
更新日期：2012-09-01 00:00:00
abstract：:The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable con...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00414-0
更新日期：2003-03-01 00:00:00
abstract：:Alpha-fetoprotein (AFP) is overexpressed in the majority of hepatocellular carcinomas (HCCs), and thus may offer attractive target for immunotherapy against this neoplasm. CD40 ligand (CD40L) is the major signal that induces B cells to efficiently present antigen to T cells, and CD40-activated B (CD40-B) lymphocyte ce...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.12.050
更新日期：2009-11-01 00:00:00
abstract：:The modern living standard has imposed upon society a situation of chronic sleep deprivation. This chronic loss of sleep affects women more than it does men. As a result, the postponement of pregnancy has become a common choice due to the priority given to social and domestic activities. For women, pregnancy represent...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.07.036
更新日期：2010-12-01 00:00:00
abstract：:SARS-CoV-2 virus has resulted in a devastating pandemic of COVID-19. Exploring compounds that could offer a breakthrough in treatment is the need of the hour. Re-positioning cheap, freely available and safe drugs is a priority. The paper proposes evidence for the potential use of diethylcarbamazine (DEC) in the treatm...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.109843
更新日期：2020-10-01 00:00:00
abstract：:Solutes concentration in the aqueous humor of the eye is highest near the ciliary processes in the posterior chamber (p.c.) and lowest near the trabecular meshwork in the anterior chamber (a.c.). The high osmotic gradient across the semipermeable iris causes it to easily move forward at this location and occasionally ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00338-9
更新日期：2003-03-01 00:00:00
abstract：:Oxidative stress plays a crucial role in a variety of clinical settings of atherogenesis, and mediates many pathways linked to atherosclerosis and inflammation. gamma-Glutamyltransferase (GGT), an enzyme responsible for the extracellular catabolism of antioxidant glutathione, may directly take part in atherogenesis an...
journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2006.04.010
更新日期：2006-01-01 00:00:00
abstract：:Silicone may, like any other adjuvant, induce an inflammatory reaction and diseases. There is no data about its use in renal transplant recipients. Increased immunogenicity of silicon may manifest by activation of both the innate and the adaptive immune system cells what promotes a chronic pro-inflammatory response. D...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2018.12.012
更新日期：2019-02-01 00:00:00
abstract：:The prevalence of adult and childhood obesity are increasing. Most of the human newborn's body fat accumulates in the last half of intrauterine life. Fat in the fetus was thought to be mostly synthesized from glucose, but now it is commonly accepted that the bulk of it is the product of placental transfer of maternal ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2018.10.022
更新日期：2019-01-01 00:00:00
abstract：:The accepted paradigms of mainstream neuropsychiatry appear to be incompletely adequate and in various cases offer equivocal analyses. However, a growing number of new approaches are being proposed that suggest the emergence of paradigm shifts in this area. In particular, quantum theories of mind, brain and consciousn...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.02.013
更新日期：2017-04-01 00:00:00
abstract：:An increase in pro-inflammatory cytokines, decrease in endothelial nitric oxide (eNO) and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones such as incretins and cholecystokinin that regulate satiety, hunger, and food intake occur in metabolic syndrome. Thus, metabolic syndrom...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.11.013
更新日期：2011-03-01 00:00:00
abstract：:It is postulated that the metabolically variable fine structure of pericellular heparan glycosaminoglycans affects the ability of these molecules to influence cell proliferation-associated proteinase-catalysed reactions occurring at cell surfaces. Evidence suggesting the possibility of a wide repertoire of glycosamino...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(83)90093-2
更新日期：1983-07-01 00:00:00
abstract：:The 'Big Bang' is used to describe the origin of the Universe. While such an event could not create itself the expression is graphic. Tissue damage, traumatic, thermal, chemical; bites; insect, animal or human are all bad, but also well known factors which favor and initiate pathogenic activity. Antedating and outrank...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90036-x
更新日期：1991-06-01 00:00:00
abstract：:Some cancer patients live many decades after diagnosis while others are not so fortunate. Understanding why this occurs is a fundamental issue in cancer research. We hypothesize that among the factors controlling favorable outcome are a class of genes that we describe as "good oncogenes". These genes have a paradoxica...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.10.015
更新日期：2011-02-01 00:00:00
abstract：BACKGROUND:The hypotheses of autoimmune, allergic or infectious etiology of severe mental illness have been reported in the scientific literature repeatedly. The main objective of this work is to study the relationship of inflammatory, autoimmunity or recent infection markers with the fact of suffering Severe Mental Di...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2019.109279
更新日期：2019-09-01 00:00:00
abstract：:Logic, a fundamental component of research in the exact sciences is often not applied in prominent fields of medical research. Investigation into the aetiopathogenesis of headache, vertigo, and fatigue--acknowledged as the commonest and amongst the most prominent and debilitating of symptoms known to mankind--may be s...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90025-a
更新日期：1990-04-01 00:00:00
abstract：:Many experimental evidences indicate that infection with Trypanosoma cruzi delays or inhibits the growth of malignant tumors in different strains of mice and in rats. These facts were verified by different workers. Although earlier workers proposed that this effect would be due to a toxin of T. cruzi, most of the accu...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0808
更新日期：2000-01-01 00:00:00
abstract：:A hypothesis is presented concerning the origin of the action of muscles in the human and animal bodies It is advanced that muscle action originates with very rapid chemical reactions known as percussion reactions. These give rise to the temporary precipitation of solids in muscle cells. The accompanying volume change...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00149-4
更新日期：2002-08-01 00:00:00
abstract：:Recent studies using a combination of isotope and balance techniques have shown that, in the postabsorptive state, the human kidney contributes substantially to overall glucose production and consumption. The kidney may contribute as much as the liver to gluconeogenesis and play an important role in the counterregulat...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1997.0655
更新日期：1999-05-01 00:00:00
abstract：:Body size and body composition have been suggested as the best explanation for the temporal trend toward early menarche over the last 100 years. There is evidence from human and animal studies that indicates that body size is not the primary factor in influencing the occurrence of menarche. The data actually show that...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(81)90124-9
更新日期：1981-11-01 00:00:00
abstract：:Posterior capsule opacification (PCO) is a debilitating and relatively common complication of cataract surgery despite modern medical and surgical advances. The pathophysiology of this condition has largely been attributed to peptide mediators, such as transforming growth factor-beta (TGFβ), epidermal growth factor (E...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.042
更新日期：2013-04-01 00:00:00
abstract：:Preliminary reports have demonstrated that anterior nucleus thalamus high-frequency electrical stimulation (ANT-HFS) is an effective treatment for patients who suffer from medically refractory epilepsy. However, its extensive application has been hampered by the high cost and the unpredictable outcome before the opera...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.06.001
更新日期：2013-09-01 00:00:00
abstract：:A hypothesis is presented describing the operation of mammalian brains on the basis of rapid percussion chemical reactions and shock waves generated by such reactions. It is shown that the products of these are various chemical compounds identified as present in the brain. The manner in which the brain deals with vari...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00296-7
更新日期：2002-12-01 00:00:00
abstract：:Normally, the transport of allergens through the intestinal epithelia to the blood is limited. It is hypothesised that if these compounds arrive in the blood circulation, they must percolate through the epithelial cell layer. Thus, food allergy (and thus atopic eczema) implies an increased intercellular leakage of the...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2004.10.018
更新日期：2005-01-01 00:00:00
abstract：:Most of the evidence of formation of amblyopia is derived traditionally from electrophysiological studies. Recently, there have been many discoveries from genetics, histopathology, biochemistry, immunology and interventional studies. On the basis of evidence gathered in the last five years, the various types of amblyo...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(97)90275-9
更新日期：1997-02-01 00:00:00
