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Effect of cigarette smoking on salivary epidermal growth factor (EGF) and EGF receptor in human buccal mucosa.

The mouth acts as a primary target for cigarette smoke which is associated with several oral diseases and cancer. The present study investigated the effect of cigarette smoking on salivary EGF and the buccal EGF receptor. Samples of whole saliva and buccal biopsy were obtained from 15 healthy volunteers (10 smokers and 5 non-smokers). The smokers smoked 20 or more cigarettes/day for more than 5 years. Salivary cotinine (a major metabolite of nicotine) was determined by radioimmunoassay (RIA). The salivary cotinine level was consistent with the self-reported smoking status (smokers, 106-530 ng/ml saliva; non-smokers, < 2 ng/ml saliva). As compared to the non-smokers, the salivary EGF concentration (determined by RIA) was 32% lower in those smokers whose salivary cotinine level was 250 ng/ml or higher (non-smokers, 2.21 +/- 0.16; smokers, 1.57 +/- 0.09 ng/ml saliva; mean +/- S.E.M., P < 0.01). There was no significant difference in 125I-labeled EGF binding to the buccal receptor between the two groups. However, EGF stimulated the autophosphorylation of a 170-kDa protein band in the sample of non-smokers, but not in the smokers. The immunoblot analysis using anti-EGF receptor antibody indicated that the smoking-related deficiency in EGF receptor autophosphorylation was due to the functional alteration of the receptor proteins. In conclusion, cigarette smoking reduces the salivary EGF level and impairs the function of buccal EGF receptor, which may be associated with the pathology of smoking-related oral disease.

Blotting, Western↗

Enhanced penetration of nitrosonornicotine across oral mucosa in the presence of ethanol.

There is evidence for synergy between tobacco and alcohol in the etiology of oral cancer but the reason for such an effect is unclear. One possible explanation is that alcohol enhances the penetration of carcinogens through the oral lining. We measured the permeability in vitro of three regions of porcine oral mucosa to the tobacco associated carcinogen, nitrosonornicotine (NNN) alone and in the presence of 5% or 50% ethanol. 50% ethanol did not significantly alter the permeability of oral mucosa to NNN except for buccal mucosa, where it was reduced. However, there was a significant increase in the permeability of gingiva and floor of mouth mucosa (but not buccal mucosa) in the presence of 5% ethanol; this increase occurred after far shorter exposures for floor of mouth than for gingiva. These results accord well with studies showing that the floor of mouth is a "high risk area" for oral carcinoma and that there is an increased relative risk of oral cancer for heavy smokers and drinkers and, in particular, for those individuals who consume beverages with a low alcohol content.

Animals↗

[Prevention and therapy of acute radiation injuries of the skin and mucosa. I. Results of a German multicenter questionnaire].

BACKGROUND: The acute radiation related morbidity is an essential factor for the patient's outcome in radiotherapy. The prophylactic and therapeutic management of acute side effects has a wide clinical range between different radiation oncology departments. In this work, it was to evaluate the remedies, which are used for prevention and therapeutic management of acute radiation related morbidity of the skin and mucosa (mouth, pharynx, esophagus, small and large bowel, rectum and vagina). METHODS: A questionnaire was sent to 130 radiotherapeutic departments in Germany in July 1995. The questionnaire had been designed with 22 open questions concerning the preventive and therapeutic management of acute radiation related morbidity of skin and mucosal sites. It has been correlated to the scoring system of the RTOG/EORTC and its German modification according to Seegenschmiedt and Sauer. The evaluation was performed anonymously. RESULTS: From 130 questionnaires, 89 (68.4%) were sent back till August 1995. All of them were evaluable. The recommendations showed a broad spectrum for each site. Especially the oral mucositis was treated in many different ways and combinations. The prevention and therapy of complicating superinfections seem to be the joint principle of most of the recommendations. CONCLUSIONS: The management of the acute radiation related morbidity has a wide clinical spectrum among different radiation therapy centers. Systematic prospectively designed investigations are necessary in order to achieve a further reduction in the radiation related acute morbidity. Therefore, a multicenter collaborative working group has been founded.

Acute Disease↗

[Morphology of the oral mucosa in rats exposed to increased phosphorus levels].

The experiments on rats kept for 1, 2, 3 and 4 months in phosphorous-producing workshops revealed the influence of elementary phosphorous and its nonorganic derivatives on the mouth mucosa tissues. At the early stages of the experiments the above agents caused the increase in the number of the epithelial layer cell elements, and strengthening of the keratosis process, leading to the development of hyperkeratosis. By the end of the experiment the development of dystrophic and atrophic processes in the epithelium were observed, which sometimes caused thinning of the epithelial layer. The connective tissue of submucous basis was characterized by microcirculation disorders and dystrophic disturbances of blood vessel walls becoming more pronounced by the end of the experiment.

Air Pollutants, Occupational↗

Biochemistry of glycosaminoglycans in the skin and oral mucosa of the rat.

Glycosaminoglycans (GAG) were extracted by digestion with papain followed by ultrafiltration and separated by cellulose-acetate electrophoresis and by chromatography of their cetyl-pyridinium complexes on cellulose microcolumns. The uronic-acid content of the tissues ranged from 0.8 to 2.4 mg/g of dry defatted tissue. Hyaluronic acid and dermatan sulphate were found in all tissues with chondroitin-4-sulphate also in skin, palatal mucosa and gingiva. There was 3-fold more hyaluronic acid in palatal mucosa than in any other tissue; it was concentrated in the antemolar rugae. A substance of presumptive salivary origin staining with alcian blue was found in cheek and floor of mouth mucosa. It migrated differently from reference GAG by electrophoresis and was not degraded by testicular hyaluronidase.

Animals↗

Penetration pathways of different compounds through epidermis and oral epithelia.

The permeability of skin and oral mucosa to various compounds has been measured but the actual pathways substances take in traversing the epithelia have not been identified. In this study, radiolabelled cholesterol, ethanol or water were placed on the surface of porcine skin, keratinized gingiva, or nonkeratinized floor of mouth mucosa, and incubated at 37 degrees C for 2 h. The tissue was then snap-frozen, and sectioned in a cryostat, picked up on precoated slides and exposed at -20 degrees C for 40 days for light microscopic autoradiography. Some tissues were freeze-dried and directly embedded in low viscosity resin and prepared for electron microscopic autoradiography. Examination of autoradiographs revealed silver grains over, or adjacent to, intercellular spaces. Counts of the grains over the extra- and intracellular compartments were made in random light and electron microscope fields. For all compounds and tissue regions, there were significantly more (p less than 0.05) grains over the intercellular spaces than over the cells. The results indicate that the intercellular compartment is the predominant route for compounds moving across the superficial barrier layer of epidermis and oral epithelia. The nature of the intercellular material is, thus, a primary determinant of epithelial permeability.

Animals↗

Oral mucosal permeability and stability of transforming growth factor beta-3 in vitro.

PURPOSE: To investigate the permeability and localization of topically applied 125I-TGF-beta3 in porcine floor-of-mouth mucosa as a function of concentration and exposure. METHODS: The 125I-TGF-beta3 diluted in three different vehicles was applied to the tissue samples mounted in perfusion cells maintained at 37 degrees C. Flux and Kp values were calculated from the perfusate collected over a 24 hour period. The quantity of 125I-TGF-beta3 present in the tissue was determined by horizontal sectioning and subsequent counting. The stability of 125I-TGF-beta3 in saliva and in the tissue was analyzed by SDS polyacrylamide gradient gel electrophoresis. RESULTS: 125I-TGF-beta3 was relatively stable in saliva and in the epithelium; approximately 50% of the total counts in the deeper epithelium were resident in the 25kDa TGF-beta3 homodimer. A steady-state flux was reached approximately 6 hours post application and Kp value was 4.0+/-0.6 x 10(-6) (mean +/- sem). Penetration of 125I-TGF-beta3 to the basal cell layer was concentration dependent but reached nanomolar concentrations even after extensive surface rinsing, representing over one-thousand fold the IC50 for epithelial cell cycle arrest. CONCLUSIONS: The data suggest that topical application of TGF-beta3 to the oral mucosa in an appropriate vehicle can provide effective therapeutic delivery to the tissue.

Absorption↗

[Effect of prodigiozan on the course of candidiasis of the oral mucosa clinically and in an experiment].

The effect of various doses of prodigiozan on Candida infection was studied under experimental and clinical conditions. Hamsters and guinea pigs were used in the experiments. Prodigiozan was administered intramuscularly to the hamsters in doses of 100 gamma/kg of the body weight 1 hour before the infection and intracutaneously to the guinea pigs in doses of 50 gamma/kg 2 days before the infection. The results showed that the drug accelerated the recovery of the animals. In complex therapy of a group of 22 patients with candidosis of the mouth mucosa of various localization prodigiozan was administered thrice in doses of 50 gamma/kg. This provided faster elimination of the pathological process.

Animals↗

Thin-layer chromatographic analyses of lipids in different layers of porcine epidermis and oral epithelium.

Frozen cryosections were cut parallel to the surface of porcine skin and palatal, buccal and floor-of-mouth mucosa so as to provide separate samples representing various epithelial layers. The samples were dried, extracted with chloroform:methanol, and the lipids were chromatographed on silica gel plates in various solvent systems. After charring, lipids were quantified with a scanning densitometer. Overall, greater differences in proportions and distributions of lipid components were evident between keratinized and non-keratinized epithelia than between epidermis and keratinized oral epithelium. For epidermis and palate there was an increase in neutral lipids, including ceramides, from the deeper layers to the surface; ceramides were most abundant in surface layers. In buccal epithelium there was a distinct increase in glycosylceramides toward the surface, and in both non-keratinized regions ceramides were present in only very small amounts. The results suggest that although neutral lipids may be associated with a superficial barrier layer in skin and oral mucosa, there are differences in the composition of this barrier between keratinized and non-keratinized epithelia.

Animals↗

[Oral transmucosal fentanyl citrate (OTFC) in the treatment of breakthrough pain].

Breakthrough pain in patients receiving opioids for pain relief is traditionally treated with opioids given orally. This, however, implies a long time to clinical effect and a long duration of action resulting in difficult titration. It is possible to give fentanyl orally for transmucosal absorption (OTFC) with a new formulation using a stick with a specially designed tablet that can be rubbed against the mouth mucosa. This gives a short time to effect and with a short duration of action. Clinical studies have shown that patient tolerance of OTFC is high and the analgesic effect is comparable to that of intravenous fentanyl, without the need for an i.v. line. Clinical indication will be breakthrough pain in patients receiving opioids for baseline pain medication.

Administration, Oral↗