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Pressure-induced ischemia. II. A metabolic study in hamster cheek pouch.

The effects of pressure-induced ischemia on energy metabolism, measured as ATP and glucose content, is studied in hamster cheek pouch. Metabolic deterioration during ischaemia is studied and after 2 h the glucose content was significantly reduced but not the ATP content, which was significantly reduced after 4 h of ischemia. Restoration of glucose levels in the cheek pouch tissue was achieved within 30 min of recirculation after release of pressure. The cellular energy metabolism is unable after 4 h of ischemia to restore ATP levels in the tissue during the 120-min of postischemic observation time. There is a difference in ability to resume normal energy metabolism after 2 and 4 h of pressure-induced ischemia.

Adenosine Triphosphate↗

Effects of iloprost, a stable prostacyclin analog, and its combination with NW-nitro-L-arginine on early events following lipopolysaccharide injection: observations in the hamster cheek pouch microcirculation.

The effects of iloprost, a stable prostacyclin analog, and of its combination with NW-nitro-L-arginine (L-NAG) on the microcirculatory changes observed in early stages of endotoxemia were investigated in male hamsters treated with Escherichia coli lipopolysaccharide (LPS). The cheek pouch was studied in vivo by means of intravital microscopy and mean arterial and venous pressures, mean arteriolar internal diameter, spontaneous arteriolar vasomotion, microvascular blood flow, macromolecular permeability, leukocyte adhesion and mean survival time were evaluated in animals treated with LPS alone or with the combination of LPS+iloprost and LPS+iloprost+L-NAG. Intravenous injection of LPS (100 mg/kg) per se elicited a significant reduction in mean arterial blood pressure (MABP) and arteriolar blood flow. The observed arterioles dilated and spontaneous vasomotion ceased. Iloprost (40 ng/kg/min) prevented LPS-induced reduction of MABP, ameliorated the decrease in arteriolar blood flow and reduced the vasodilation. Arteriolar vasomotion was reduced but it did not cease. The combination of L-NAG (0.5 mg/kg) + iloprost (40 ng/kg/min) with LPS (100 mg/kg) did not improve the results obtained with iloprost alone, except that it prevented the vasodilation and the vasomotion ceased 1 h after the bolus injection of LPS+L-NAG. The mean survival time compared to LPS alone (57 +/- 7 h) was significantly increased by the combination of LPS+iloprost (102 +/- 6 h) and it did not change significantly with the combination L-NAG+iloprost (64 +/- 9 h). Topical addition of iloprost (10 ng/kg/min) evoked an early increase in macromolecular permeability and a significant decrease in leukocyte adhesion compared with animals treated with topical LPS (0.7 microgram/ml/min) alone. The combination of L-NAG+iloprost (1.3 + 10 ng/ml/min) enhanced the early increase in macromolecular permeability even further, tended to increase the macromolecular permeability and evoked a smaller decrease in leukocyte adhesion than the one observed with iloprost combined with LPS. Our results, in the hamster cheek pouch microcirculation, suggest that the use of prostacyclin could be beneficial in the treatment of early changes in endotoxic shock, but L-NAG showed no benefit in this preparation.

Animals↗

Effect of L-arginine on reactivity of hamster cheek pouch arterioles during diabetes mellitus.

The goal of this study was to determine whether exogenous application of L-arginine could restore impaired agonist-induced increases in arteriolar diameter during diabetes mellitus. We used intravital microscopy to examine reactivity of cheek pouch arterioles (50 microns in diameter) in nondiabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. In nondiabetic hamsters histamine (1.0 and 5.0 microM) dilated cheek pouch arterioles by 15 +/- 1 and 22 +/- 1%, respectively, and substance P (50 and 100 nM) dilated arterioles by 14 +/- 3 and 21 +/- 4%, respectively. In addition, dilatation of arterioles in response to histamine and substance P in nondiabetic hamsters was abolished by application of an enzymatic inhibitor of nitric oxide synthase (L-NMMA). In contrast, histamine- and substance P-induced increases in arteriolar diameter were markedly reduced in diabetic hamsters. Histamine (1.0 and 5.0 microM) dilated arterioles by only 5 +/- 1 and 4 +/- 2%, respectively, and substance P (50 and 100 nM) dilated arterioles by only 6 +/- 2 and 5 +/- 3%, respectively (p < 0.05 vs. nondiabetic hamsters). Nitroglycerin produced similar vasodilatation in nondiabetic and diabetic hamsters. Next, we examined whether exogenous application of L-arginine (100 microM) could restore impaired histamine- and substance P-induced increases in arteriolar diameter in diabetic hamsters. We found that L-arginine did not restore altered nitric oxide synthase-dependent vasodilatation in diabetic hamsters. These findings suggest that short-term diabetes mellitus alters agonist-induced increases in arteriolar diameter. In addition, the mechanism of altered arteriolar reactivity during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.

Administration, Buccal↗

Effects of a calcium antagonist and of the adrenergic system on spontaneous vasomotion and mean arteriolar diameter in the hamster cheek pouch: influence of buflomedil.

Intravital microscopy of the hamster cheek pouch microvasculature was used for in vivo studies of the effects of diltiazem (calcium antagonist, group I), prazosin (alpha 1-adrenergic receptor antagonist, group III), rauwolscine (alpha 2-adrenergic receptor antagonist, group V), phenylephrine (alpha-adrenergic receptor agonist, group VII) and isoproterenol (beta-adrenergic receptor agonist, group IX) in a concentration range of 10(-9)-10(-5) M and their combination with 10(-7) M of buflomedil (groups II, IV, VI, VIII and X) on mean arteriolar internal diameter and spontaneous vasomotion. All drugs were applied topically. Vasomotor activity was studied in 270 arterioles (internal diameter range 20.0-75.0 microns) of 60 preparations. Diltiazem dose dependently increased the microvascular diameter and reduced and ultimately abolished the vasomotion frequency and amplitude. Addition of buflomedil did not significantly change the vasodilation evoked by diltiazem and potentiated its depressive effect on vasomotion frequency and amplitude. Prazosin dose-dependently increased the arteriolar diameter and reduced the vasomotion frequency and amplitude. Addition of buflomedil potentiated both the vasodilation elicited by prazosin and the reduction in vasomotion frequency and amplitude. Rauwolscine tended to elicit vasoconstriction at lower concentrations (10(-9) and 10(-8) M) and vasodilation at higher concentrations (10(-5) M) and significantly reduced the vasomotion frequency and amplitude. Addition of buflomedil potentiated both the vasodilation and the reduction in vasomotion frequency, but tended to increase the vasomotion amplitude. Phenylephrine significantly decreased the mean arteriolar internal diameter, moderately decreased the vasomotion frequency and did not significantly change the vasomotion amplitude. Addition of buflomedil totally blocked the vasoconstriction elicited by phenylephrine, potentiated the reduction in vasomotion frequency and amplitude when combined with lower concentrations of phenylephrine (10(-9)-10(-7) M) and restored the vasomotion frequency and amplitude when combined with higher concentrations of phenylephrine (10(-6) and 10(-5) M). Isoproterenol significantly increased the mean arteriolar diameter and reduced the vasomotion frequency and amplitude. Addition of buflomedil did not significantly change either the vasodilation or the reduction in vasomotion frequency and amplitude. The effects observed with buflomedil on the hamster cheek pouch microcirculation further support its properties as a competitive inhibitor of alpha-adrenergic receptors, not selective for either the alpha 1- or alpha 2-adrenergic receptor subtype, and as a weak calcium antagonist.

Adrenergic Agonists↗

Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch.

Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II.

Angiotensin I↗

The oxygen sensitivity of hamster cheek pouch arterioles. In vitro and in situ studies.

We tested the hypothesis that a parenchymally derived mediator is required for arterioles to exhibit oxygen sensitivity. To that end, the parenchyma was dissected and removed from around hamster cheek pouch arterioles, and the oxygen sensitivity of these "aparenchymal arteriolar segments" was studied, either in vitro, after cannulation, or in situ. Arteriolar segments in situ with and without parenchyma had similar oxygen sensitivities (20% constriction as Po2 increased from 15 to 150 mm Hg). Arteriolar occlusion, which eliminated blood flow in the in situ aparenchymal segments, did not eliminate their oxygen sensitivity. The oxygen-induced constriction in the occluded aparenchymal segments was blunted but not eliminated by covering the segments with glass plates to prevent changes in Po2 from occurring around these vessels. We hypothesized that propagation of a portion of the oxygen response might explain the persistent response in the covered and occluded arteriolar segments. Oxygen sensitivity could be shown in only 32% of the in vitro cannulated arterioles (16% mean constriction as Po2 increased from 20 to 150 mm Hg). In contrast, 75% of aparenchymal arterioles were sensitive to changes in Po2 in situ. These data led us to reject the hypothesis that a parenchymally derived mediator is absolutely required for arterioles to exhibit oxygen sensitivity. We infer that the oxygen sensitivity of hamster cheek pouch arterioles results partially or totally from the local action of oxygen on some component of the arteriolar wall or blood, that a portion of the oxygen response may be the result of a propagated phenomenon, and that the oxygen-sensitive component is fragile and is easily lost in preparation for in vitro measurements or in cannulation. It is emphasized that the O2 sensor need not reside in vascular smooth muscle.

Animals↗

Dose-related effects of adenosine and bradykinin on microvascular permselectivity to macromolecules in the hamster cheek pouch.

The hamster cheek pouch preparation was used to assess microvascular permselectivity responses to three vasodilating agents: bradykinin, adenosine, and papaverine. Fluorescein isothiocyanate-dextran 150 was injected intravenously as a macromolecular tracer. To quantify changes in permeability, we calculated fluorochrome clearance values from the ratio of suffusate to plasma fluorescein isothiocyanate-dextran 150 concentration. The microcirculation was recorded on videotape, using epifluorescence and bright-field light microscopy. Topical application of bradykinin elicited dose-dependent increases in macromolecular permeability. Adenosine also augmented permeability in a dose-dependent fashion. The increases in tracer clearance, relative to control, were 9.4 nl/min for 10(-5) M adenosine and 39.4 nl/min for 10(-4) M adenosine. The standard error for these doses was 1.5 nl/min. Adenosine, 10(-6) M, did not alter permeability. The increment in clearance induced by 10(-4) M was comparable to that of bradykinin, 8 X 10(-7) M. Pretreatment with phenidone had no effect on the permeability response mediated by 10(-5) M adenosine. Topical application of papaverine enhanced the transvascular exchange of macromolecules in one-half of the preparations examined. Comparable doses of adenosine were approximately three times as effective. This study indicated that adenosine, like bradykinin, is capable of modifying microvascular permeability responses in the hamster cheek pouch. This modulatory effect appears to be due to a direct action on the postcapillary microvascular membrane.

Adenosine↗

A comparison of some of the permeability characteristics of intact and tape-stripped hamster cheek pouches in vitro.

Cheek pouches were removed from anesthetized hamsters and were either tape-stripped or left intact and then mounted in Ussing chambers, where they were bathed in Krebs-Ringer bicarbonate saline. A potential difference could be measured across all pouches and was stable for over an hour across the unstripped pouches. The electrical resistance across the unstripped pouches was high (8960 omega.cm2), whereas the resistance across the tape-stripped pouches was significantly lower (p less than 0.01), suggesting that these pouches are likely to be more permeable than the unstripped pouches. Reflection coefficients of urea, ethanol, and glycerol were derived by means of streaming potentials. Values for intact pouches were all close to 1 and for tape-stripped pouches were 0.938, 0.822, and 0.509, respectively. Permeability coefficients for urea and ethanol across intact and tape-stripped pouches were, respectively, 12.5 X 10(-9)cm/min; 27.6 X 10(-9) cm/min; 2325 X 10(-9)cm/min; and 28471 X 10(-9) cm/min. The hamster cheek pouch has a high electrical resistance; it is an impermeable structure in which the keratin layer appears to provide a major barrier to the passage of water, ions, and certain solutes.

Animals↗

The folded trapezius flap for through-and-through cheek defects.

A through-and-through defect of the cheek is a reconstructive challenge--functionally, technically, and cosmetically. The goal of reconstruction is to reliably and expediently bridge a poorly vascularized gap with healthy tissue. Since 1979, five patients have undergone folded trapezius flap reconstruction of the cheek. Despite a history of radiation in four of the five, all flaps have healed and complications have been minimal. The key to success seems to be careful attention to the venous drainage. This technique provides a one-stage reconstruction of a difficult surgical defect.

Adult↗

[Results of radiotherapy in a series of 250 carcinomas of the mucosal surface of the cheek (author's transl)].

This paper presents the results of a retrospective clinical study of 250 cases of monocentric carcinoma of the mucosal surface of the cheek, i.e. all the primaries treated by radiotherapy at our Institute between January 1948 and December 1965. Neoplastic lesions found at follow-up were regarded as marginal recurrences if in the proximity of the treated area and as secondary tumors in other cases. From 1948 to 1957 conventional radium therapy was the usual treatment for the primary tumor whereas from 1958 to 1965 cobalt teletherapy was given most frequently. Surgery was reserved for lymph node metastases when present on clinical examination. In our experience radiotherapy is effective in cancers of the mucosal surface of the cheek, for it checked local spread in 50.9% of cases, however treated and regardless of initial clinical appearance, whereas in the T1-T2 cases the local failure rate dropped to 35.8%. The higher the T level the greater are the difficulties confronting radiotherapy; for more extensive lesions appropriate combination therapy (radiosurgical) in line with the well-defined rules explained in the text is useful. In our experience radiotherapy yields good long term results regardless of T level and even in the more unfavorable cases. Our study confirms the low rate of lymph spread of these carcinomas: over half of the patients were N0 before treatment; only 56.7% of the patients receiving surgical treatment on the neck had histologically positive lymph nodes; there were very few neck recurrences at follow-up; the presence of suspect or frankly metastatic nodes on clinical examination, being movable and homolateral (N1), did not worsen the prognosis. However, considering the techniques used for irradiation of the primary, some patients received a substantial dose to the neck; hence radiotherapy probably played its part in the low rate of neck metastases.

Aged↗

Increased apoptosis during morphogenesis of the lower cheek teeth in tabby/EDA mice.

In wild-type (WT) mice, epithelial apoptosis is involved in reducing the embryonic tooth number and the mesial delimitation of the first molar. We investigated whether apoptosis could also be involved in the reduction of tooth number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA mice. Using serial histological sections and computer-aided 3D reconstructions, we investigated epithelial apoptosis in the lower cheek dentition at embryonic days 14.5-17.5. In comparison with WT mice, apoptosis was increased mainly mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear to play any causal role in positioning inter-dental gaps. Analysis of the present data suggests that the increased apoptosis in Ta mice is a consequence of impaired tooth development caused by a defect in segmentation of dental epithelium.

Animals↗

Psychometric properties of the Revised Cheek and Buss Shyness Scale.

Although the Revised Cheek and Buss Shyness Scale (RCBS; Cheek, 1983) is widely used, its psychometric properties largely are unknown. In this investigation, we examined the normative data, factor structure, internal consistency, test-retest reliability, and convergent/discriminant validity of the RCBS using a sample of 261 university students. Results provided strong support for the stability of normative data over time, reliability of the measure, and its predicted associations with contemporary measures of shyness, social anxiety, and related constructs. Although support was obtained for a unifactorial conceptualization of shyness, an exploratory factor analysis revealed an alternative 3-factor solution that was supportive of a previously proposed meta-analytic model of shyness (Jones, Briggs, & Smith, 1986) and was consistent with other prominent shyness theories (Buss, 1980; Pilkonis, 1977a, 1977b; Zimbardo, 1977). This factor model was replicable on a holdout sample, and there were some data to support the discriminant validity of factors.

Adolescent↗

The numb cheek syndrome: a sign of infraorbital neuropathy.

Three patients with skin cancer had numbness isolated to one cheek, in the distribution of the infraorbital nerve. Hypesthesia also involved the medial and lateral upper incisors and canine teeth, and adjacent gingiva, sparing the more posterior teeth and gums. The molar and premolar teeth and gums are innervated by the posterior and middle superior alveolar nerves; because these structures were spared, the pathologic process was localized to the infraorbital foramen, and we could exclude involvement of the maxillary division more proximally. In two patients, cheek numbness heralded recurrent squamous cell carcinoma. Analogous anatomy at the mental foramen should help distinguish intracranial leptomeningeal from local mandibular lesions producing isolated numbness of the chin.

Aged↗

Characteristics of monkey tryptase purified from cheek pouch vascular tissues.

Tryptase purified from rat and dog tissues has been reported, although the characteristics of these enzymes are different from human tryptase. For pathophysiological studies of human tryptase, studies on species that have a similar tryptase to humans is needed. In this study, we purified monkey tryptase from cheek pouch vascular tissues using heparin affinity and gel filtration columns. The monkey tryptase, which had a molecular weight of 130 kDa by gel filtration, consisted of a tetramer of 33 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The N-terminal sequence showed high homology with tryptases from other species. The optimum pH and temperature were 7.5-9.0 and 25-40 degrees C, respectively. The enzyme was labile in high-KCl buffer, and the optimum KCl concentration was 0.1 M. The enzyme activity was completely inhibited by diisopropyl phosphorofluoridate and leupeptin but not by soybean trypsin inhibitor and alpha-antitrypsin. The enzyme hydrolyzed vasoactive intestinal peptide but did not affect angiotensin I, somatostatin and bradykinin. In the present study, we first isolated monkey tryptase from cheek pouch vascular tissues and showed that the characteristics of monkey tryptase are very similar to those of human tryptase.

Animals↗

Histomorphology of the hamster cheek pouch.

Histomorphology of the cheek pouch was studied in 14 hamsters by light and transmission electron microscopy. The cheek pouch wall was devoid of any lymphatic tissue and dense subepithelial tissue (i.e. the lamina propria) would render lymph drainage almost impossible and might constitute impermeable morphological barrier for non-recognition of transplants evoking a host immune response. Because in the literature it was reported that there is absence of any arteriovenous anastomoses on the pouch wall, and interruption of arterial supply failed to alter the growth rate of tissue grafts, we speculated that epidermal growth factors present in the saliva could play a role in maintaining the growth of tissue transplants.

Animals↗

Evaluation of the photosensitizer Tookad for photodynamic therapy on the Syrian golden hamster cheek pouch model: light dose, drug dose and drug-light interval effects.

We have evaluated the efficacy of the new photosensitizer (PS) Tookad in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection-light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels.

Animals↗

Keloid heterograft in the hamster (Mesocricetus auratus) cheek pouch, Brazil.

PURPOSE: To study the integration of keloid heterograft in hamster (Mesocricetus auratus) cheek pouch. METHODS: The sample is formed by 18 male hamsters, heterogenic ones, aged between 10 and 14 weeks. Keloid fragments were obtained from keloid scars of the breast region of adult female mulatto patient. Each hamster received keloid fragments into both of its pouches, in a total of 36 grafted fragments. Animals were distributed into 6 groups for having their grafts assessed in the days 5, 12, 21,42, 84, and 168. A macroscopic assessment is performed by comparing the pouch containing the grafted fragment, at each time point, with the same pouch in the immediate post surgical moment through a comparison of standardized photographs. Under microscope, the presence of blood vases is considered within the conjunctive tissue of the grafted fragment, as a criterion of its integration. Other events, as keratin secretion, the presence of cellular infiltrated, epithelium and keloid collagen fibers aspects are also analyzed. RESULTS: Macroscopy reveals intensive vascularization of the pouch up to 12 days from the transplantation and the presence of constant dark brown pigmentation on the grafted keloid fragments. In microscopy, the integration of keloid fragments is considered by the presence of blood capillary vases within conjunctive tissue. The presence of intensive cellular inflammatory type infiltrated up to 12 days is also observed, as well as the remaining of keloid epithelium up to 21 days, and the appearing of melanocytes from the day 42. CONCLUSION: Hamster cheek pouch represents, a priori, an experimental model for the investigation of keloid.

Animals↗

Primary cutaneous T-cell lymphoma involving the cheek: an infant case with a unique clinicopathologic feature.

We report a clinicopathologic feature of primary cutaneous T-cell lymphoma (CTCL) in a five-year-old boy with increasing swelling of his cheek since two years of age. Histologically, an infiltrate of atypical lymphoid cells with mature T-cell phenotype and clonality was prominent from the dermis to the subcutaneous tissue of the cheek. Although little effect was seen with aggressive multidrug-combined chemotherapy, therapy with interferon-alpha and steroids achieved a prolonged remission. This patient may provide important clues to understanding the clinicopathologic feature of rare primary CTCL in young children.

Cheek↗