Cell turnover

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Salicylic acid has a keratolytic effect, thus eliminating superficial pigmented keratinocytes and stimulating cells turnover. This superficial peeling allows TCA to act a low concentration to remove pigmented keratinocytes through papillary dermis (see Fig. 14.12). 

Anthony IC, Bell JE (2008) The neuropathology of HIV/AIDS. Int Rev Psychiatry 20 15-24 Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Does drug abuse alter microglial phenotype and cell turnover in the context of advancing HIV infection Neuropathol Appl Neurobiol 31 325-338... 

Martinez-Marcos A., Ubeda-Banon I. and Halpem M. (2000). Cell turnover in the vomeronasal epithelium evidence for differential migration and maturation of subclasses of vomeronasal neurons in the adult opossum. J Neurobiol 43, 50-63. 

Wilson K.C. and Raisman G. (1980). Age-related changes in the neurosensory epithelium of the mouse vomeronasal organ extended period of post-natal growth in size and evidence for rapid cell turnover in the adult. Brain Res 185, 103-113. 

Prostaglandins, one of the most important epithelial growth factors, inhibit gastric acid secretion and have numerous mucosal protective effects, the most important of which include the stimulation of both mucus and phospholipid production, promotion of bicarbonate secretion, and increased mucosal cell turnover. Damage to the mucosal defense system is the primary method by which HP or NSAIDs cause peptic ulcers. 

Keratinocyte proliferation is central to the clinical presentation of psoriasis. Keratinocytes are skin cells producing keratin which act as a skin barrier. Increased keratinocyte cell turnover (hyperkeratosis) results in the characteristic thick scaly skin lesions seen in patients with psoriasis.10,11 Hyperkeratosis results from immune derangements. 

Benzoyl peroxide is easy to use and recommended as first-line therapy in the treatment of mild to moderate noninflammatory acne. Benzoyl peroxide has a comedolytic effect that increases the rate of epithelial cell turnover and helps to unclog blocked pores. It also has antibacterial activity against P. acnes, which appears to be the main reason for the effectiveness of this product.13... 

Retinoids, which are highly effective in the treatment of acne, stimulate epithelial cell turnover and aid in unclogging blocked pores. Retinoids also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis.8 Because of these comedolytic and antiinflammatory effects, topical retinoids are recommended as first-line treatment for mild to moderate comedonal and inflammatory acne.3 While success is seen with monotherapy, using a retinoid in combination with benzoyl peroxide or topical antibacterials is also an appropriate and effective therapeutic treatment option.3 Tretinoin, adapalene, and tazarotene are topical retinoids available for use in the treatment of acne. Table 62-2 describes the strengths and formulations of these agents. 

In acute uric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts and ureters. This syndrome is a well-recognized complication in patients with myeloproliferative or lymphopro-liferative disorders and results from massive malignant cell turnover, particularly after initiation of chemotherapy. Chronic urate nephropathy is caused by the long-term deposition of urate crystals in the renal parenchyma. 

Tretinoin (a retinoid topical vitamin A acid) is a comedolytic agent that increases cell turnover in the follicular wall and decreases cohesiveness of cells, leading to extrusion of comedones and inhibition of new comedo formation. It also decreases the number of cell layers in the stratum corneum from about 14 to about five. 

Anthralin products must be applied only to affected areas because contact with uninvolved skin may result in excessive irritation and staining, which usually disappear within 1 to 2 weeks of discontinuation. Staining of affected plaques indicates a positive response because cell turnover has been slowed enough to take up the stain. 

From the comparison by Nyman et al. between plasma Hp level and different red cell destruction indices (half-life of CrB1-tagged erythrocytes, endogenous CO formation, stercobilin (urobilin) excretion in feces) it is evident that anhaptoglobinemia is a very common, but not an invariable accompaniment of increased red cell turnover. The exceptions are possibly persons with increased Hp synthesis. Individual differences in efficiency to destroy red cells outside the circulation without Hb return may be reflected by the wide normal variation range of plasma Hp as well by the promptness with which anhaptoglobinemia develops on even slight increase in Hb turnover. 

Health consequences of procyanidins in the human diet are relatively unknown, but the toxicity for human beings may be similar to the toxicity observed in experimental animals (12). Bender and Mohammidiha (31) proposed that increased fecal nitrogen from rats fed diets containing large quantities of cooked legumes was due to increased gastrointestinal mucosal cell turnover, rather than poor... 

Scheding S, Ersoez 1, Hartmann U et al. Peripheral blood telomere length measurements indicate that hematopoietic stem cell turnover is not significantly increased in whole blood and apheresis platelets donors. Transfusion 2003 43 1089 1095. 

Brummendorf TH, Mak J, Sabo KM et al. Longitudinal studies of telomere length in feline blood cells implications for hematopoietic stem cell turnover in vivo. Exp.Hematol. 2002 30 1147 1152. 

Bmmmendorf TH, Balabanov S. Telomere length d3mamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 2006 20 1706-1716. 

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

Tretinoin or retinoic acid is the acid form of vitamin A. Actually it is the all-trans isomer of retinoic acid. It is an effective topical agent for acne vulgaris. Its mechanism of action is believed to be associated with increased epidermal cell turnover. Some 10% of the topically applied dose is absorbed, metabolized by the liver and excreted in the urine and bile. To be effective tretinoin should be applied in a concentration that results in mild irritation and erythema. Patients should be advised to avoid or minimize sun exposure and use a protective sun screen as animal studies have raised some concern about possible carcinogenic effects under the influence of ultraviolet radiation. There are no indications that topical tretinoin is associated with an increased risk for birth defects. 

Continuous cell division is foimd, for example, in stem cells, which serve as precursors for other cells, and in tissue in which dying cells must be replaced. This requires the continuous effects of mitogenic signals. In this case, cell division must ensme homeostasis of the cell structure or the tissue. An increase in the cell number through cell division compensates for loss of cells that die as a part of normal cell turnover or that are eliminated by programmed cell death, or apoptosis. 

The anemia of hyperthyroidism is usually normochromic and caused by increased red blood cell turnover. The anemia of hypothyroidism may be normochromic, hyperchromic, or hypochromic and may be due to decreased production rate, decreased iron absorption, decreased folic acid absorption, or to autoimmune pernicious anemia. LDH, lactic dehydrogenase AST, aspartate aminotransferase. 

Retinoic acid has several effects on epithelial tissues. It stabilizes lysosomes, increases ribonucleic acid polymerase activity, increases prostaglandin E2, cAMP, and cGMP levels, and increases the incorporation of thymidine into DNA. Its action in acne has been attributed to decreased cohesion between epidermal cells and increased epidermal cell turnover. This is thought to result in the expulsion of open comedones and the transformation of closed comedones into open ones. 

The remarkable efficacy of topical corticosteroids in the treatment of inflammatory dermatoses was noted soon after the introduction of hydrocortisone in 1952. Numerous analogs are now available that offer extensive choices of potencies, concentrations, and vehicles. The therapeutic effectiveness of topical corticosteroids is based primarily on their antiinflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover. The general pharmacology of these endocrine agents is discussed in Chapter 39. 

Dopamine oxidation. In Parkinson s disease, cell death is localised to the dopamine-producing cells of the substantia nigra. Radicals are produced during the oxidation of DA, but whether the formation of these species is responsible for neuronal cell death or occurs as a consequence of cell turnover has not been established. Haque et al. have observed semiquinones from DA and is meta-... 

Acrylonitrile is toxic at high dose in several organs, which is possibly related to its glutathione-depleting activity. This toxicity might lead to tmnour formation by an indirect mechanism, although no data to support this are evident from the available toxicity data, such as increased cell turnover or DNA labelling. 

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