Cellular mitosis

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Taxol i is a naturally occurring substance isolated from the Pacific yew tree Taxus brevifolia), which has been approved for clinical treatment of cancer patients. Taxol enhances polymerization of tubuhn and the consequent formation of stable microtubules, inhibiting cellular mitosis. 

During cellular mitosis, DNA and certain cellular proteins bundle together into chromosomes, which are visible under a microscope. These chromosomes duplicate themselves and then divide evenly into two separate cells called daughter cells. 

Retinoids are differentiation agents related to or derivative of vitamin A. They bind to a cellular protein that facilitates their transfer from the cytoplasm to the nucleus where they are believed to increase DNA, RNA, and protein synthesis and to affect cellular mitosis. 

Colchicine binds to tubulin and prevents its polymerization into microtubules, subsequently disrupting microtubule function. Consequently, it alters nuclear structure, intracellular transport, and cytoplasmic motility, ultimately causing cell death. Colchicine is a potent inhibitor of cellular mitosis. 

Griseofulvin is exclusively active against dermatophytes, through inhibition of cellular mitosis. It also binds to host cell keratin and reduces its degradation by fungal keratinases. It may also interfere with dermatophyte DNA production. 

It has been noticed that somatal cell lines cultured in vitro reproduce about 20 to 50 times and then the cells die. This has prompted biologists to specnlate that there is a natural end to multicellular BU in vivo. One reason for this may be events in the process of cellular mitosis, as chromosomes are split and replicated. Replication requires an involved series of steps, and includes RNA priming, DNA primase, DNA polymerase, and DNA ligase in an intricate set of maneuvers. These steps, however, are not able to replicate the end of the DNA strand. Errors in the replication process can... 

The initial tissue response when a biomaterial is implanted in the body is dependent on release of specific growth factors. It has been indicated by Frost [1] that the inevitable bone injury resulting from surgery and the presence of an implant will release various types of growth factors that will sensitize cells and promote cellular mitosis. This is a general healing response that will result in growth of all sorts of local connective tissues, bone as well as various types of soft tissue. 

It is now believed that much of the pharmacological activity of these drugs derives from their direct interaction with double-helical deoxyribonucleic acids (Gale et al, 1972 Lown, 1977). By perturbing DNA structure, these drugs may inhibit the synthesis of nucleic acids and interfere with cellular mitosis. The antitumor activity of many of these drugs likely involves this inhibition of DNA synthesis. 

Methotrexate belongs to the class of antimetabolites. As a derivative of folic acid it inhibits the enzyme dihydrofolate reductase resulting in a decreased production of thymidine and purine bases essential for RNA and DNA synthesis. This interruption of the cellular metabolism and mitosis leads to cell death. 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

Microtubules are universally present in eukaryotes from protozoa to the cells of higher animals and plants (Porter, 1966 Hardham and Gunning, 1978 Lloyd, 1987), but they are absent in mammalian erythrocytes and in prokaryotes. Microtubules participate in a number of cellular functions including the maintenance of cell shape and polarity, mitosis, cytokinesis, the positioning of organelles, intracellular transport to specific domains, axoplasmic transport, and cell locomotion. The diversity of microtubule fimctions suggests that not all microtubules are identical and that different classes of microtubules are present in different cell types or are localized in distinct domains in the same cell type (Ginzburg et al., 1989). 

Eehner In the epidermis it is quite reproducible. After mitosis 13, when the syncytial division cycle is stopped, cellularization occurs followed by a pulse of string expression that allows cells to go through mitosis 14. Then they go immediately into S phase and wait in the next G2 phase until the next pulse of string comes up, driving mitosis 15. After mitosis 15, they go again immediately into S phase and wait in G2 until string comes up, triggering the final division. 

Since cellular immunity results in the release of chemotactic lymphocytes that in turn enhance phagocytosis, a deficiency in cellular immunity may also result in chronic infections. Cellular immunity is mediated by T cells, macrophages, and NK cells involved in complex compensatory networks and secondary changes. Immunosuppressive agents may act directly by lethality to T cells, or indirectly by blocking mitosis, lymphokine synthesis, lymphokine release, or membrane receptors to lymphokines. In addition, cellular immunity is involved in the production and release of interferon, a lymphokine that ultimately results in blockage of viral replication (Table 15.4). Viruses are particularly susceptible to cytolysis by T cells since they often attach to the surface of infected cells. Thus, immunosuppression of any of the components of cellular immunity may result in an increase in protozoan, fungal, and viral infections as well as opportunistic bacterial infections. 

Among the many phosphorus compounds selected by Mitchell and his collaborators may be mentioned tetrasodium 2-methyl l 4-naphthohydroquinone diphosphate (VTH). A concentration of 4 x 10 6 M of (VIII) produced a 50 per cent mitotic inhibition using chick fibroblasts in tissue culture. It is thought that the inhibition of the entry of cells into mitosis depends on the blockage of cellular synthetic processes involving phosphoryla-... 

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