Medical principles and practice : international journal of the Kuwait University, Health Science Centre
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Chronic obstructive pulmonary disease (COPD) is a major global health problem which is increasing throughout the world and a major cause of death. However, current therapies fail to prevent disease progression or mortality. The mainstay of current drug therapy are long-acting bronchodilators; several longer-acting inhaled beta(2)-agonists and muscarinic antagonists (and combinations) are now in development. ⋯ Broad-spectrum anti-inflammatory drugs may be more effective, and include inhibitors of the enzymes phosphodiesterase-4, p38 mitogen-activated protein kinase, NF-kappaB kinase and phosphoinositide 3 kinase-gamma and -delta, but side effects will be a major limitation so that inhaled delivery may be necessary. Perhaps the most promising approach is reversal of corticosteroid resistance through increasing histone deacetylase-2 activity. This might be achieved by theophylline-like drugs, phosphoinositide 3 kinase-delta inhibitors, more effective antioxidants and non-antibiotic macrolides.
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Variation in the quality or quantity of nutrients consumed during pregnancy can exert permanent and powerful effects upon the developing fetus. This programming of fetal development is emerging as a new risk factor for non-communicable diseases of adulthood, including coronary heart disease and the metabolic syndrome. Epidemiological studies show that indicators of nutritional deficit in pregnancy are associated with greater risk of diabetes and cardiovascular mortality. ⋯ It is noteworthy that minor perturbation of maternal nutritional status can programme fetal development. It is suggested therefore that programming is a product of altered expression of key genes. This drives the tissue remodelling response and future disease risk.
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The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy. Development of chemoresistance is a persistent problem during the treatment of local and disseminated disease. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. ⋯ Adjuvant therapy with P-glycoprotein inhibitors and, in specific instances, the use of growth factor and protein kinase C inhibitors are newer experimental approaches that may also prove effective in abrogating or delaying onset of resistance. Gene knockout using antisense molecules may be another effective way of blocking drug resistance genes. Conversely, drug resistance may also be used to good purpose by transplanting retrovirally transformed CD34 cells expressing the MDR gene to protect the bone marrow during high-dose chemotherapy.
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Androgens and estrogens are primarily made from dehydroepiandrosterone (DHEA), which is made from cholesterol via four steps. First, cholesterol enters the mitochondria with the assistance of the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia (lipoid CAH), a potentially lethal disease in which virtually no steroids are made. ⋯ The ratio of the 17,20 lyase to 17alpha-hydroxylase activity of P450c17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated posttranslationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase (POR), the presence of cytochrome b5 and the serine phosphorylation of P450c17. Mutations of POR are a new, recently described disorder manifesting as the Antley-Bixler skeletal dysplasia syndrome, and a form of polycystic ovary syndrome.
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It is well known that smoking contributes to the development of lung cancer and cardiovascular disease, and there is weighty evidence that it has a considerable influence on oral health. Smoking has many negative effects on the mouth, including staining of teeth and dental restorations, reduction of the ability to smell and taste, and the development of oral diseases such as smoker's palate, smoker's melanosis, coated tongue, and, possibly, oral candidosis and dental caries, periodontal disease, implant failure, oral precancer and cancer. ⋯ Quantitatively, however, importance has been attached to periodontitis, which affects a large proportion of the population, and during recent years more attention has been given to implant survival rates. Dentists have an important role to play in preventing the harmful effects of smoking in the mouth, and consequently smoking counselling should be as much a part of the dentist's job as plaque control and dietary advice.