Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches.

Inflammatory stimuli result in the production of cutaneous eicosanoids, which are known to contribute to the process of tumor promotion. Cyclooxygenase (COX), the rate-limiting enzyme for the production of prostaglandins (PG) from arachidonic acid, exists in at least two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays various physiological roles, whereas increased COX-2 expression is known to occur in several types of epithelial neoplasms. Enhanced PG synthesis is a potential contributing factor in UVB-induced nonmelanoma skin cancers (NMSC). Increased COX-2 staining occurs in murine skin neoplasms after chronic exposure to carcinogenic doses of UVB. In this study, immunohistochemical and Western blot analyses were employed to assess longitudinally COX-2 expression in a standard mouse UVB complete carcinogenesis protocol and in human basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). During UVB irradiation of mice, COX-2 expression consistently increased in the hyperplastic skin, the benign papillomas and the SCC. COX-2 expression was also increased in human actinic keratoses, SCC and BCC as well as in murine SCC and BCC. The pattern of COX-2 expression was quite variable, occurring in a patchy distribution in some lesions with staining confined mainly to suprabasal cell layers. In general, COX-2 expression progressively became more extensive in benign papillomas and well-differentiated murine SCC. The staining was predominantly cytoplasmic and perinuclear in some focal areas in tissue stroma around both murine and human tumors. Western blot analysis confirmed negative COX-2 expression in normal skin, whereas acute UVB exposure resulted in increased enzyme expression, which continued to increase in developing papillomas and SCC. Because of the evidence indicating a pathogenic role for eicosanoids in murine and human skin neoplasms, we performed studies to assess the anti-inflammatory and anticarcinogenic effects of green tea extracts, which are potent antioxidants. Acute exposure of the human skin to UVB (minimum erythema dose x 4) caused a transient enhancement of the COX-2 expression, which reverted to baseline within hours; however, in murine skin the expression persisted for several days. Pretreatment with the topically applied green tea extract (1 mg/cm2) largely abrogated the acute COX-2 response to UVB in mice or humans. In summary, enhanced COX-2 expression serves as a marker of epidermal UVB exposure for murine and human NMSC. These results suggest that COX-2 inhibitors could have potent anticarcinogenic effects in UVB-induced skin cancer.

Chronic exertional rhabdomyolysis.

This article presents a brief description of what is known about the cause and pathogenesis of chronic intermittent rhabdomyolysis in horses. Clinically applicable diagnostic tests and published results in affected horses, prophylaxis, and treatment of the acute case are discussed.

Bioelectric potential gradients may initiate cell cycling: ELF and zeta potential gradients may mimic this effect.

When a number of experimental studies in bioelectromagnetics were reviewed, those in which weak, exogenous extremely low frequency (ELF) fields were applied in fixed juxtaposition to their target tissues, were found to initiate mitogenesis or mitogenesis-related signals more successfully than when the target tissue moved freely during the irradiation. It is suggested that ELF fields in fixed juxtaposition to their target tissue and implanted foreign bodies or endogenous tissues with a significant zeta potential, mimic bioelectric fields generated at wounds. When the potential is high enough, they assist healing by moving cells into the wound and stimulating quiescent cells at the wound margin to cycle. Electrophoresis may help the initial migration of cells into the wound to form a clot, and migration of fibroblasts and epithelial cells from the wound margin. When exposed for a long time in a fixed juxtaposition to a potential gradient too weak to show in situ microelectrophoresis along the cell membrane surface, surface particles may coalesce to form microclusters, where like-charged surface particles are in close proximity, and growth factor receptor oligomerization and other cycle-initiating reactions are facilitated.

Attitudes toward health risks and sunbathing behavior.

Sunbathing confers the benefits of looking and feeling good but presents the long-term risk of skin cancer. In a disguised experiment exploring attitudes toward sunbathing by British adults, participants were asked to rate their willingness to take a hypothetical new drug (with different levels of risk) that would make them look and feel good. One aspect of the resulting risk profiles was significantly related to a positive attitude to open-air sunbathing but not to sunbed use, possibly because it was erroneously thought that using a sunbed is not risky. The well-established finding that women are more cautious was confirmed; the risk function for men was curvilinear, in contrast to women, who were willing to increase their risk linearly over their lifetime.

Hepatic intracellular pH in vivo using F-quene 1 and 19F NMR spectroscopy.

Intracellular pH (pHi) has been determined in vivo in livers from anaesthetized rats using both 31P NMR and 19F NMR spectroscopy. In the 31P NMR study pHi, determined from the chemical shift of endogenous Pi, was found to be 7.26 +/- 0.02. In the 19F NMR study on a separate group of animals pHi was determined from the chemical shift of F-Quene 1 infused via the portal vein and found to be 7.18 +/- 0.01. In approximately half of the 19F NMR studies no 19F signal could be detected in the liver probably because of the two probes could be caused by different intra- or intercellular distributions or by unknown effects of F-Quene 1 on metabolism.

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals.

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.

Image latency and recall as functions of array size.

A comparison of image latencies and recall as a function of increasing arrays of objects involved three groups of subjects listening to descriptions of arrangements of objects and responding when they had visualized each array as a whole. After each latency response, one group of subjects indicated if they had visualized all the objects, another group free recalled, and a third group had no additional task. A fourth group recalled the arrays immediately after the end of the description. Increasing array size, and hence the demands on the resources of the visual imagery system, produced a concomitant exponential-like deterioration in performance according to the latency and recall measures. However, the deterioration in recall only started above arrays of four objects compared with an increase in latencies across these array sizes; so the latency function is not produced by the unavailability of information, at least for smaller array sizes. The group who immediately recalled did not remember spatial positional information concerning the middle serial positions of six-object arrays as well as the group who underwent wholistic visualization prior to recall, indicating that the wholistic visualization process can facilitate the coding of spatial information.