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Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.

9,10-Dimethyl-1,2-benzanthracene↗

Acute infusion of nicotine potentiates norepinephrine-induced vasoconstriction in the hamster cheek pouch.

Although cigarette smoking and the components of cigarette smoke appear to alter nitric oxide synthase-dependent dilation of blood vessels, the effect of these substances on constrictor responses of resistance arterioles has not been examined. Thus the goal of this study was to examine the effect of a major component of cigarette smoke-that is, nicotine-on constrictor responses of cheek pouch arterioles. The diameter of cheek pouch arterioles (approximately 50 microm in diameter) was measured by using intravital microscopy. We examined the responses of arterioles to angiotensin II, arginine vasopressin, norepinephrine, and the thromboxane analog U-46619 before and after treatment with vehicle (saline solution), N(G)-monomethyl-L-arginine (L-NMMA; 1.0 micromol/L), or nicotine (2.0 microg/kg/min i.v. for 30 minutes followed by a maintenance dose of 0.35 microg/kg/min for 30 minutes). Topical application of angiotensin II (0.01 and 0.1 nmol/L), arginine vasopressin (1.0 and 10 pmol/L), norepinephrine (1.0 and 10 nmol/L), and U-46619 (0.01 and 0.1 nmol/L) produced marked reproducible constriction of cheek pouch arterioles in hamsters treated with vehicle. Topical application of L-NMMA potentiated constrictor responses of arterioles to the high dose of arginine vasopressin (28%+/-4% versus 36%+/-4%; P<.05) and to both doses of norepinephrine (14%+/-1% and 24%+/-2% versus 19%+/-1% and 31%+/-3%; P<.05). The infusion of nicotine did not alter responses to angiotensin II, arginine vasopressin, or U-46619 but modestly potentiated vasoconstriction in response to norepinephrine (12%+/-2% and 22%+/-2% versus 14%+/-2% and 26%+/-2%; P<.05). These findings suggest that the synthesis/release of nitric oxide may modulate constrictor responses of cheek pouch resistance arterioles to selected agonists. In addition, nicotine, at levels observed in smokers, may potentiate norepinephrine-induced vasoconstriction. We suggest that preservation/potentiation of vasoconstrictor responses may contribute to the pathogenesis of vascular abnormalities associated with cigarette smoking.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Functional and aesthetic reconstruction of full-thickness cheek, oral commissure and vermilion.

PURPOSE: This paper presents surgical techniques for reconstruction of the cheek, oral commissure and vermillion in the repair of full-thickness cheek defects after resection of buccal-mucosal squamous cell carcinoma. PATIENTS AND METHODS: Four reconstructions in one-stage surgery with either a free radial forearm flap or a rectus abdominis musculocutaneous flap for cheek and oral commissure were carried out. There were combined with a new approach for vermillion advancement flaps. Most challenging was the need not only for morphological reconstruction of the orifice, but also for physiological reestablishment of sphincteric and sensory functions in the vermillion. RESULTS: Morphological and physiological reconstruction of the lip with sphincteric and sensory functions was attained. CONCLUSION: This valuable reconstruction technique was demonstrated in large, full thickness defects involving the cheek, oral commissure and vermilion.

Aged↗

The Z-plasty transposition flap for reconstruction of the middle cheek.

BACKGROUND: Large defects of the middle cheek may prove difficult to repair. Too wide for primary closure, such defects pose challenging reconstructive options because there are no cosmetic unit boundaries in which to camouflage incision lines without resorting to widely undermined flaps. OBJECTIVE: This article summarizes our experience with the Z-plasty and double Z-plasty transposition flaps for reconstruction of the cheek. METHODS: The Z-plasty transposition flap was used immediately after Mohs micrographic surgery to repair 14 defects of the middle cheek caused by basal cell carcinoma (n = 12) or squamous cell carcinoma (n = 2). In all cases, primary closure of the defect would have resulted in excessively long scars, scars oriented perpendicular to relaxed skin tension lines, and/or free-margin distortion. In 4 of these cases, a double Z-plasty was used. RESULTS: The cosmetic and functional outcomes were judged from good to excellent by patient and surgeon. No cases of infection occurred. In one patient, minor superficial tip necrosis healed without incident. A "spit" subcutaneous suture at one flap tip of another patient left a small nodular scar, which was primarily excised and healed well. CONCLUSIONS: The Z-plasty and double Z-plasty transposition flaps offer excellent primary reconstructive modalities for the repair of geographically isolated defects of the cheek that are large or misoriented for primary side-to-side closure. The theoretical and practical geometric characteristics of the Z-plasty transposition require preparation and practice to achieve consistently satisfying results.

Basal Cell Carcinoma↗

The evolution of techniques for reconstruction of full-thickness cheek defects.

Our experience with 20 full-thickness cheek reconstruction in 17 patients over the past 27 years is presented. The evolution of techniques for management of full-thickness cheek defects reflects our gradual appreciation of the longitudinal artery concept within axial and musculocutaneous flap units. During the 1950s, defects were managed by random flaps. Popularization of the forehead flap and introduction of the medially based deltopectoral flap during the 1960s heralded the current application of axial flaps. The 1970s saw an explosion of new techniques, including the musculocutaneous flaps and microvascular free tissue transfers, based on the longitudinal vessel concept. A method simultaneously employing the pectoralis major musculocutaneous flap for intraoral lining and the deltopectoral flap for external coverage has been described. A modification of the latissimus dorsi free flap to allow a one-stage watertight closure of large full-thickness cheek defects has been outlined. Our challenge for the 1980s lies in the improvement of techniques to reanimate the reconstructed cheek.

Adolescent↗

Cheek and eyelid reconstruction: the resurrection of the angle rotation flap.

BACKGROUND: Reconstruction of larger cheek and eyelid defects may pose a dilemma for surgeons, since flaps used in reconstruction may be difficult to design, be unreliable, require extensive dissection, and result in neck scarring. Consequently, the authors wish to simplify and expand an overlooked flap, the angle rotation flap, which moves tissue in both a medial and upward direction. METHODS: Twenty patients with cheek and eyelid defects were treated by the angle rotation flap. In this flap design, the angle designed below the ear was closed primarily and the neck tissue previously there was rotated upward and forward to lie in front of the ear. The portion of the flap that was in front of the ear was transposed to the lower lid/cheek area. This flap was modified in several patients by elevation in the deep plane and first-stage tissue expansion. RESULTS: In all cases, good coverage was provided for medial cheek and lower eyelid defects with minimal scarring on the neck. There were no flap losses of any kind. There were no major complications, and all minor incidences were treated by minimal procedures without long-term sequelae. CONCLUSION: The modified angle rotation flap is a useful tool for cheek and eyelid defects.

Arteriovenous Malformations↗

The hamster cheek pouch as a convenient ectopic site for studies of uterine morphogenesis and endocrine responsiveness.

The Syrian hamster cheek pouch was evaluated as a convenient transplantation site for studies of estrogen-dependent uterine growth and morphogenesis. At one month of age, hosts were either ovariectomized (Ovex) or ovariectomized and estrogen implanted (Ovex+E2), and at the same time the uterus from a 7-day old untreated donor was transplanted into the host's right cheek pouch. Periodic inspection (by simple eversion of the pouch) revealed viable transplants in the majority of hosts for both groups, and clear evidence of estrogen-dependent transplant growth that continued for at least 9 months. At that time, weight of the transplanted uterus was comparable to that of a given host's own in situ uterus, but uteri at both sites weighed six to eightfold more in Ovex+E2 hosts than in Ovex hosts. Histological analysis also revealed similar degrees of endometrial atrophy in Ovex hosts and hypertrophy/hyperplasia in Ovex+E2 hosts for both in situ and transplanted uteri. Furthermore, while only scant and rudimentary endometrial glands developed in both in situ and transplanted uteri within Ovex hosts, uteri at both sites within the Ovex+E2 hosts were riddled with cystic glandular structures and exhibited marked leukocytic infiltration. These data demonstrate that neonatal uteri transplanted to the hamster cheek pouch will grow, differentiate and follow an endocrine-responsive morphogenetic program that is quantitatively and qualitatively consistent with that of the host's in situ uterus. Lastly, we were able to cleanly separate epithelium from the stroma of 5-day old hamster uteri, reassociate the two tissues in vitro, transplant the recombinants into cheek pouches of adult female hamsters and subsequently observe growth and maintenance of a generally normal uterine morphology and differentiated function.

Animals↗

Cheek-neck advancement-rotation flaps following Mohs excision of skin malignancies.

The cheek-neck advancement-rotation flap has proved extremely useful for delayed reconstruction of the face following the microscopically controlled surgical excision (MCSE) of skin malignancies. We have recently used these flaps successfully to repair combined defects of the cheek and nose in eight patients, isolated cheek defects in six patients, combined defects of the cheek and lips in two patients, and isolated defects of the nose, temple, and an antral cutaneous fistula in each of three patients. Defects as large as 6.0 X 10.0 cm have been closed in one stage with this flap. This flap is extremely hearty and its scars can be well concealed. It is especially valuable in the elderly patient and should always be considered as one of the options for reconstruction of the face following MCSE of skin malignancies.

Aged↗

An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch.

Topical antigen challenge in cheek pouches of immunized hamsters led to an acute inflammatory reaction which was characterized by intravital microscopy. The response consisted of short-lasting arteriolar spasm, followed by leakage of plasma, vasodilation, and accumulation of leucocytes. Several observations indicated that the reaction was due to mast cell activation. Thus, a very similar inflammatory response was seen after challenge with compound 48/80, and both antigen and compound 48/80 degranulated the numerous mast cells present in the cheek pouch. In addition, fluorescein-labelled antigen bound specifically to mast cells in cheek pouches of immunized animals, also suggesting the presence of mast cell-fixed antigen-specific antibodies, possibly immunoglobulin E. However, although antigen and compound 48/80 caused similar microvascular responses, cross-desensitization experiments indicated that the two stimuli activated mast cells via different mechanisms. The histamine antagonist mepyramine, which abolished plasma leakage induced by exogenous histamine, substantially inhibited the increase of microvascular permeability evoked by antigen or compound 48/80, but did not appear to affect the vasospasm and leucocyte accumulation. It is concluded that the hamster cheek pouch may be a most useful tool for investigation of dynamic microvascular events during allergic mast cell-dependent inflammation.

Acute-Phase Reaction↗

A new preparation for microcirculatory studies of the hamster cheek pouch.

Existing methods of preparing the hamster cheek pouch for observation under an intravital microscope have several disadvantages. The everted method, described by Duling (Microvasc. Res. 5: 423-429, 1973), appears to restrict blood flow by placing unnatural tension on the retractor muscle and by requiring an incision in the tip of the pouch. The method of Yamaki et al. (Microvasc. Res. 21: 299-301, 1981) requires an incision in the tip of the pouch and complete disconnection of the retractor muscle. The chamber method of Greenblatt et al. (Microvasc. Res. 1: 420-432, 1969) has a limited optical resolution because the tissue cannot easily be transilluminated with properly condensed light. We have devised a less traumatic method of preparing the pouch, which eliminates these disadvantages. The hamster is anesthetized, and a thin, glass support plate is inserted into the left cheek pouch. The plate is constructed and positioned so that it does not restrict flow to any part of the pouch. The free end of the plate is secured to the animal stage. An incision is made in the skin to expose the cheek pouch, and the loose, avascular connective tissue investing the pouch and the retractor muscle is removed. The pouch is positioned at an angle of 20 degrees from the hamster's body in a temperature-controlled chamber over a standard microscope condensor system. Throughout both surgical and experimental procedures, the pouch is superfused with Ringer-bicarbonate solution at 37.5 degrees C. This preparation minimizes surgical trauma and allows the entire vascular supply to the cheek pouch to be studied.

Animals↗

Response of hamster cheek pouch microcirculation to endothelin and endothelin receptor antagonists.

Our goal was to examine the effects of endothelin-1 and endothelin-3 on hamster cheek pouch arterioles in vivo in the absence and presence of endothelin receptor antagonists. Endothelin-1 (0.1, 1.0 and 10 pM) and endothelin-3 (0.1 and 1.0 nM) produced dose-related constriction of cheek pouch arterioles which was inhibited by the endothelin ETAB receptor antagonist PD 142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp) and endothelin ETA receptor antagonist PD 147953 [FR 139317: (hexahydro-1H-azepinyl)carbonyl-Leu-(N-Me)-D-Trp- D-2-Pya]. The thromboxane analogue, U-46619 (0.1 and 1.0 nM) also produced dose-related constriction of cheek pouch arterioles, but in contrast to endothelin-1 and endothelin-3 this vasoconstriction was not abolished by endothelin receptor antagonists. These findings suggest that endothelin-1 and endothelin-3 produce marked constriction of cheek pouch arterioles which appears to be mediated by activation of endothelin ETA receptors.

Amino Acid Sequence↗

Microvascular pressure distribution and responses of pulmonary allografts and cheek pouch arterioles in the hamster to oxygen.

Despite extensive investigations of the pulmonary circulation using both in vitro and in vitro preparations, few direct microcirculatory studies have been made. Consequently, the mechanisms involved in the response of the pulmonary microvasculature to changes in oxygen tension remain unclear. The present study represents the first direct observation of the responses in pulmonary microvessels to alterations in oxygen tension. Neonatal lung tissue was transplanted into the hamster cheek pouch using a chamber technique. Both tissues were characterized with respect to their microvascular pressure profile and vascular response to hypoxia. The results showed the two tissues to be remarkably different. Small pulmonary and cheek pouch arterioles exhibited opposite responses to changes in oxygen environment; hypoxia elicited a constriction of pulmonary arterioles, but a dilation of cheek pouch arterioles. Pulmonary capillary pressure, although comparable to that measured in the intact lung (13 mm Hg), was substantially lower than cheek pouch capillary pressure, which was within the range of that described for several systemic vascular beds. The microcirculatory effects of oxygen on both tissues were confined to the arteriolar segments. The characteristics of this pulmonary microcirculation are such that it is a unique model for further physiological and pharmacological studies.

Animals↗

Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch.

The effects of a clinically used purified micronized flavonoid fraction (S 5682) containing 90% diosmin and 10% hesperidin on increased microvascular permeability induced by histamine, bradykinin, and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. The authors also investigated the effects of S 5682 on macromolecular permeability increase and leukocyte adhesion during ischemia-reperfusion by using the same preparation. S 5682, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for ten days at 20 mg/kg/day (10 mg/kg twice a day). Fluorescein isothiocyanate (FITC)-labeled dextran (mol wt 150,000) was given intravenously, thirty minutes after completion of the cheek pouch preparation. The leukocytes were stained by continuous IV infusion of acridine orange (0.5 mg/kg/minute). Histamine (2 microM), bradykinin (1 microM), and LTB4 (0.01 microM), applied topically for five minutes, increased the number of fluorescent vascular leakage sites in postcapillary venules. A temporary ischemia with total circulatory arrest of the cheek pouch was obtained by clamping the neck of the everted pouch. The maximum number of leaky sites (per cm2 in the prepared area) that occurred either at five minutes after the beginning of each topical application or ten minutes after the onset of reperfusion was quantified in ultraviolet light microscopy. The results from 60 animals divided into 10 groups of 6 animals each are presented as means +/- SEM. In comparison with vehicle, S 5682 significantly inhibited the macromolecular permeability increasing effect of histamine (343.5 +/- 22.3 versus 207.5 +/- 32.0 leaks/cm2; P < 0.01), bradykinin (345.2 +/- 19.0 versus 206.2 +/- 21.6 leaks/cm2; P < 0.01), and LTB4 (353.3 +/- 27.5 versus 242.7 +/- 33.6 leaks/cm2; P < 0.05). At reperfusion, after thirty minutes of ischemia, S 5682 significantly decreased the observed macromolecular permeability (103.6 +/- 15.4 versus 42.6 +/- 9.3 leaks/cm2; P < 0.01). Flavonoid-treated animals also displayed a statistically significant lower number of adhering leukocytes to the venular endothelium (83.5 +/- 9.5 versus 48.4 +/- 12.3 per 6 mm2; P < 0.05). These results demonstrate that oral administration of S 5682 for ten days at 20 mg/kg body weight/day had a protective effect against leakage of macromolecules after application of permeability-increasing substances and during ischemia-reperfusion in the cheek pouch microvasculature. Since firm leukocyte attachment to the endothelial wall and subsequent emigration of leukocytes into the interstitium is a mechanism for tissue damage during inflammation, attenuation of this phenomenon during conditions of ischemia-reperfusion can in part explain previous observations that this purified micronized flavonoid fraction decreases edema formation. The present data illustrating the inhibitory effect of a clinically relevant dose of S 5682 on the inflammatory processes induced in this in vivo model of microcirculation may serve as a rational basis to explain its clinical efficacy.

Administration, Oral↗

Hamster cheek pouch carcinoma: effect of incision and cortisone on growth, invasion, and metastasis.

After cheek pouch carcinomas were induced in hamsters by the application of dimethylbenzanthracene (DMBA) to the right pouch for 13 weeks, the animals were divided into four groups and observed for seven more weeks. The control group received no further treatment, two experimental groups had incisional biopsies performed on tumors in their pouches, one of these also received injections of cortisone throughout the 20-week experimental period, and a fourth group received cortisone only. The wet weights of the cancerous cheek pouches were determined, and the submandibular and parotid salivary glands with associated cervical lymph nodes, the lungs, and the liver were examined with light microscopy. The cancerous pouches of the animals that received cortisone weighed significantly less than those of animals that received no cortisone but had incisional biopsies of the tumors. There was no significant difference in the degree of histodifferentiation of the tumors among the four groups. The animals in the two groups that received cortisone had significantly more tumors that were invasive than did the animals that did not receive cortisone. Cervical lymph node metastasis occurred in 21% to 38% of the animals but was not significantly different in the four groups. Distant metastases to the lungs or the liver were not found. Incisional biopsy of the tumors stimulated local growth of the cheek pouch tumors, and systemic cortisone administration produced more invasive cheek pouch tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Inoculation of Lacazia loboi into the subcutaneous tissue of the hamster cheek pouch.

The subcutaneous tissue of the hamster cheek pouch, a site of immunologic privilege, has been used to investigate the potential infectivity of different types of parasites. It has been demonstrated that the implantation of fragments of lesions induced by the fungus Lacazia loboi, the etiologic agent of Jorge Lobo's disease, into the subcutaneous tissue of the hamster cheek pouch resulted in parasite multiplication and dissemination to satellite lymph nodes16. Here we describe the evolution of lesions induced by the inoculation of the isolated fungus into this immunologically privileged site. The morphology of the inflammatory response and fungal viability and proliferation were evaluated. Inoculation of the fungus into the cheek pouch induced histiocytic granulomas with rare lymphocytes. Although fungal cells were detected for a period of up to 180 days in these lesions, the fungi lost viability after the first day of inoculation. In contrast, when the parasite was inoculated into the footpad, non-organized histiocytic lesions were observed. Langhan's giant cells, lymphocytes and fungal particles were observed in these lesions. Fungal viability was observed up to 60 days after inoculation and non-viable parasites were present in the persistent lesions up to 180 days post-inoculation. These data indicate that the subcutaneous tissue of the hamster cheek pouch is not a suitable site for the proliferation of Lacazia loboi when the fungus isolated from human tissues is tested.

Animals↗

Effects of chlorhexidine on the structure and permeability of hamster cheek pouch mucosa.

This study examined the effects of chlorhexidine (CHD) on the clinical appearance, morphology, and in vitro permeability of hamster cheek pouch mucosa. The cheek pouches were treated daily for 3 weeks with topical applications of saline, 0.2% CHD, or 2.0% CHD. Treatment with 2.0% CHD resulted in the formation of discrete white lesions in every animal in the group, whereas no changes were identified in any animal treated with 0.2% CHD or saline. Upon microscopic examination it was determined that treatment with 2.0% CHD resulted in a statistically significant (P less than 0.01) increase in epithelial thickness, when compared to the other groups, and the lesions were found to consist of hyperplastic areas of epithelium with associated inflammatory cell accumulations. Daily treatments with 2.0% CHD, 0.2% CHD or saline had no effect on the very low permeability of cheek pouch mucosa to 14C-CHD. However, treatment with 2.0% CHD resulted in decreased permeability to 3H2O (P less than 0.05) when compared to the other groups. Treatment with 2.0% CHD also resulted in a thickened permeability barrier (P less than 0.01), as determined using a tracer, horseradish peroxidase. It is concluded that topical applications of 0.2% T CHD have no detectable effect on cheek-pouch mucosa while applications of 2.0% CHD result in hyperplasia and a decrease in mucosal permeability. Our results suggest that CHD should be used with caution clinically and at a concentration of 0.2% or less.

Administration, Topical↗

Rat cheek gland compounds: behavioural response to identified compounds.

Cheek gland secretions from sexually mature and reproductively active male and female laboratory rats (Wister strain), Rattus norvegicus albinus were analysed by gas chromatography/mass spectroscopy. Alkanes, aliphatic acids esters and alcohols were identified in the secretions. Cheek gland preparation from males contained predominantly three compounds, viz. di-n-octyl phthalate (I); 1,2-benzene diacarboxylic acid butyl (2-ethyl hexyl) ester (II); and 1,2 benzene dicarboxylic acid (2-methylpropyl) ester (III) whereas in the cheek gland of females two compounds, viz, 1,2-benzene dicarboxylic acid (2-methylpropyl) ester (I); and 2,6,10 dedecatrien-1-ol, 3,7,11-trimethyl-(Z, E) (II) were the major fractions. The identified compounds were tested for odour preferences. Compounds II and III of males and I and II of females attracted both male and female conspecifics. By contrast, compound I from males only attracted females. The level of attraction also varied from compound to compound. The results suggest that cheek gland secretions have pheromonal functions.

Animals↗

Gore-Tex implant as tissue filler in cheek-lip groove rejuvenation.

The cheek-lip grooves, often referred to as nasolabial folds, are one of the facial characteristics most commonly complained about by patients in all age groups. A variety of methods for correction have been proposed, using implants or autografts. Some of the methods have relied on diminishing the crest lateral to the groove thus camouflaging the depth of the cheek-lip fold. These procedures have proven to be of limited effect, either because of the amount of correction obtained or because they are short-lasting. The Gore-Tex implant proved its safety and biocompatibility over the past decade as a vascular graft. The characteristics of this implant material are described and compared to other commonly used synthetic implants. A surgical technique of applying the Gore-Tex soft tissue patch in facial aesthetic surgery, particularly in cheek-lip rejuvenation, is presented. This technique has been applied in 17 consecutive patients for the correction of prominent cheek-lip grooves with a follow-up period of eight months. Results showed satisfactory improvement without significant complications.

Cheek↗