Pouch Tissue Research Articles

Regulation of flow and wall shear stress in arteriolar networks of the hamster cheek pouch.

Our purpose was to define arteriolar network hemodynamics during moderate increases in interstitial adenosine or nitric oxide in the hamster (n = 34, pentobarbital sodium 70 mg/kg) cheek pouch tissue. The network consists of a feed arteriole (approximately 12-microm diameter, approximately 800-microm length) with three to six branches. Observations of diameter, red blood cell flux, and velocity were obtained at the feed before the branch and within the branch. A comparison of baseline with suffused adenosine or sodium nitroprusside (SNP) 10(-9) to 10(-5) M showed the following. First, diameter change was heterogeneous by agonist, did not reflect the expected dilatory response, and was related to location within the network. With adenosine, upstream branch points constricted and those downstream dilated, even at 10(-5) M. With SNP, upstream branch points dilated, whereas those downstream constricted. Second, with adenosine, changes in diameter, flux, and velocity together resulted in no change in wall shear stress until 10(-5) M. Wall shear stress was not maintained at a constant level with Nomega-nitro-L-arginine (10(-5) M), suggesting a role for flow-dependent diameter changes with adenosine. With SNP, diameter change correlated with the baseline (before SNP) shear stress conditions.

Optimal methods for fluorescence and diffuse reflectance measurements of tissue biopsy samples.

In developing fluorescence spectroscopy systems for the in vivo detection of pre-cancer and cancer, it is often necessary to perform preliminary testing on tissue biopsies. Current standard protocols call for the tissue to be immediately frozen after biopsy and later thawed for spectroscopic analysis, but this process can have profound effects on the spectroscopic properties of tissue. This study investigates the optimal tissue handling methods for in vitro fluorescence spectroscopy studies. The epithelial tissue of the Golden Syrian hamster cheek pouch was used in this study. Three specific experiments were carried out. First, the fluorescence properties of tissues in vivo and of frozen and thawed tissue biopsies were characterized at multiple excitation wavelengths spanning the ultraviolet-visible (UV-VIS) spectrum. Next, comparison of tissue fluorescence emission spectra in vivo, ex vivo (immediately after biopsy), and after the freeze and thaw process were systematically carried out at the excitation wavelengths corresponding to the previously identified fluorescence peaks. Lastly, intensities at the excitation and emission wavelength pairs corresponding to the fluorescence peaks were measured as a function of time after biopsy. Diffuse reflectance measurements over the UV-VIS spectrum were also made to evaluate the effects of oxygenation, blood volume, and scattering on the tissue fluorescence at these different excitation-emission wavelengths. This study indicates that the freezing and thawing process produces a significant deviation in intensity and lineshape relative to the in vivo fluorescence emission spectral data over the entire UV-VIS range between 300 and 700 nm. By contrast, examination of ex vivo emission spectra reveals that it closely preserves both the intensity and lineshape of the in vivo emission spectra except between 500 and 700 nm. The observed deviations can be explained by the diffuse reflectance measurements, which suggest increased hemoglobin deoxygenation and wavelength dependent changes in scattering in ex vivo tissues, and increased total hemoglobin absorption in the frozen and thawed samples. Furthermore, it was found that over a time window of 1.5 hours, spectroscopic changes brought about by degradation of the tissue due to biopsy or other factors are significantly smaller (10-30% variations in intensity) than those associated with the freezing and thawing process (50-70% decrease in intensity). It was found that the effects of freezing and thawing on the fluorescence properties of tissue are greater than any changes brought about by degradation of tissue over a time frame of 90 minutes after biopsy. Performing ex vivo fluorescence measurements within a reasonable time window has the advantage of more accurately reproducing the clinically relevant in vivo conditions in the case of the hamster cheek pouch tissue. Therefore, in tissue biopsy studies, the tissue sample should ideally be maintained in an unfrozen state prior to measurement.

Isolation of chymase complexed with physiological inhibitor similar to secretory leukocyte protease inhibitor (SLPI) from hamster cheek pouch tissues

A low molecular weight protein complexed with chymase was isolated from hamster cheek pouch tissues. This protein had an apparent molecular mass of about 10 kDa on SDS-PAGE and the N-terminal sequence showed some homology to secretory leukocyte protease inhibitor (SLPI), which is known as the predominant inhibitor of neutrophil elastase and cathepsin G. Remarkably enhanced inhibition of chymase activity was achieved in the presence of heparin, indicating that the functional property was also similar to SLPI. These findings suggest that this SLPI-like protein is a candidate for a physiological inhibitor of chymase.

Coffee enhances the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinomas

In this study, we examined the effect of roasted coffee extract on 7,12-dimethylbenz[a]anthracene (DMBA)-induced buccal pouch carcinogenesis in male Syrian hamsters using lipid peroxidation, reduced glutathione (GSH) and glutathione peroxidase (GPx) activity as biomarkers of chemoprevention. Forty male hamsters were divided into four groups of 10 animals. The right buccal pouches of the animals in Group 1 was painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in Group 2 painted with DMBA as in Group 1, received in addition 2 ml of 8% black coffee extract intragastrically three times a week on days alternate to DMBA application. Group 3 animals received coffee extract as in Group 2. Animals in Group 4 received neither DMBA nor coffee extract and served as control. The hamsters were sacrificed after an experimental period of 14 weeks. Biochemical measurements were carried out on tumour and normal pouch tissues. Administration of roasted coffee extract had no preventive effect on DMBA-induced oral cancer as revealed by the higher mean tumour volume and tumour burden compared to animals painted with DMBA alone. Diminished lipid peroxidation in the oral tumour tissue was accompanied by a significant increase in the levels of GSH and GPx. The results of the present study suggest that coffee exerts a tumour enhancing effect when administered during DMBA-induced hamster buccal pouch carcinogenesis.

Telomerase activity during 7,12-dimethylbenz [a] anthracene-induced hamster buccal pouch carcinogenesis

Objective: To investigate the roles of telomerase activity (TA) in relation to hamster buccal pouch tumor progression. Methods: male hamster were treated three times weekly with 0.5% of 7, 12-dimethyl-benzanthracene (DMBA) over a IS weeks experimental period. Hamsters were sacrificed at 3, 6, 9, 12 and 15 weeks after treatment. Telomerase activity of hamster buccal pouch tissue were measured along with the analyses of the formation of DMBA-induced hamster buccal pouch tumors. Results: DMBA-induced squamous cell carcinomas were found at the 6th week after dosing. Telomerase activity elevation began at the 3rd week and was increasing to a plateau at the 12th week. Conclusion: Our results show that telomerase activity in the target tissue may be detected at the early stage of the DMBA-induced hamster buccal pouch tumor formation and suggests that telomerase activity may be used as a biomarker for an early clinical detection of buccal pouch cancer.

Inhibition of 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis by S-allylcysteine

Consumption of garlic has been reported to be associated with decreased risk of cancer. We used the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinoma model to assess the oral chemopreventive potential of S-allylcysteine (SAC), a water-soluble constituent of garlic. Hamsters were divided into four groups of six animals each. The right buccal pouches of the animals in group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in group II were painted with DMBA as in group I and in addition received 200 mg/kg body weight SAC intragastrically three times a week on days alternate to DMBA application. Group III animals received SAC as in group II. Animals in group IV received neither DMBA nor SAC and served as control. The hamsters were killed after an experimental period of 14 weeks. Biochemical measurements were carried out on tumour and normal pouch tissues. Measurement of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone for 14 weeks developed well-differentiated squamous cell carcinomas. Diminished lipid peroxidation in the oral tumour tissue was accompanied by a significant increase in the levels of GSH, GPx and GST. Administration of SAC significantly suppressed DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms. The results of the present study suggest that garlic may exert its chemopreventive effects by modulating lipid peroxidation and enhancing the levels of GSH, GPx and GST.

Immunolocalization and adenoviral vector-mediated manganese superoxide dismutase gene transfer to experimental oral tumors.

The anti-oxidant enzyme system protects cellular macromolecules against damage from reactive oxygen species. One component of this system, manganese superoxide dismutase (MnSOD), has also been shown to display tumor suppressor gene-like activity. The purpose of this study was to examine changes in MnSOD expression during hamster cheek pouch carcinogenesis, and the effects of MnSOD overexpression using an adenoviral vector. Tumor induction was carried out using 7,12-dimethylbenz[alpha]anthracene. Animals were killed at periodic intervals, and cheek pouch tissues were excised and examined for MnSOD expression by immunohistochemistry and digital image analysis. We observed a reduction in MnSOD expression as early as 2 weeks after the start of carcinogen application. Low MnSOD expression persisted until the end of the 23-week experimental period. Solid hamster cheek pouch carcinoma xenografts were then established in nude mice. An adenoviral vector encoding the human MnSOD gene was delivered to the xenografts by direct injection. We observed high, immediate expression of MnSOD in the xenografts that persisted for 10 days following cessation of viral construct delivery. Delivery of the MnSOD construct resulted in a maximal 50% reduction in tumor growth compared with untreated controls. Our results suggest that MnSOD may be a tumor suppressor gene in the hamster cheek pouch model system.

Bacteria in pouch tissue

Bacteria in pouch tissue

CXC and CC chemokine expression in inflamed and non-inflamed pelvic ileal pouch tissue

Background and aims Pouchitis is the major long-term complication after ileal pouch–anal anastomosis (IPAA) in patients operated on for ulcerative colitis. The cause is unknown, but both the history of ulcerative colitis and increased bacterial concentration are important factors. Chemokines are mediators for the recruitment of inflammatory cells to the site of inflammation. This study examined the tissue expression of a panel of specific chemokines and the corresponding recruitment of inflammatory cells in IPAA tissue with and without inflammation and after antibiotic treatment.

Appearance and Regression of Rat Pouch Tissue

Fibrosis, a consequence of tissue repair, can become a final common pathway to organ failure, if progressive. Prevention and regression of organ fibrosis represent targets of considerable interest. The natural fate of fibrosis differs among various tissues being either persistent, progressive or regressive. Cellular and molecular responses involving myofibroblasts (myoFb), a phenotypically transformed fibroblast-like cell of considerable functional diversity, is involved in collagen turnover at sites of repair, where they govern the fate of fibrosis. Insights gained from the natural regression of established fibrous tissue may offer strategies to remove unwanted fibrosis in failing organs. In the present study, we addressed the temporal sequence to various components of collagen synthesis and degradation involved in the appearance and subsequent regression of pouch tissue induced in the rat by subcutaneous injection of air followed by instillation of the phorbol ester croton oil. Pouch tissue was collected on day 2, 4, 10, 14, 21, 28 and 35 (n=6 at each time point). Activities of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) were determined by zymography and reverse zymography, respectively; collagen accumulation by hydroxyproline concentration; gene expression of TIMP-1 or tissue inhibitor of MMP-1, type I collagen and transforming growth factor-β1(TGF-β1) byin situhybridization; TGF-β1concentration by sandwich enzyme-linked immunosorbant assay (ELISA); and myoFb and its phenotypes by immunohistochemistry using antibodies toα-smooth muscle actin (α-SMA), vimentin or desmin. During pouch tissue formation, we found: (1) pouch weight increased progressively from day 2 to day 14 and then declined progressively thereafter; (2) type I collagen mRNA expression, barely detectable at day 2, increased at day 4, together with tissue hydroxyproline concentration (P<0.05) reaching a peak on day 10, and gradually decreased thereafter in association with declining tissue hydroxyproline concentration; (3) mRNA expression and concentration of TGF-β1, detectable at day 2, significantly (P<0.05) increased at day 4, reached a peak at day 10, and gradually declined thereafter; (4) MMP-1 activity, low at day 2, increased continually over the course of 35 days; (5) TIMP-1 mRNA, detectable at day 2 and significantly (P<0.05) increased at day 4, gradually decreased thereafter; (6) activity of TIMP-1 increased continuously from day 2 to day 14 and then was markedly reduced thereafter; and (7) myoFb were first observed in pouch tissue at day 4 and became more extensive thereafter with their phenotype changing over time. Early appearing myoFb (day 4, 10, 14, and 21) expressedα-SMA and vimentin (VA phenotype), while later appearing cells (day 28 and 35) additionally expressed desmin (VAD phenotype). Thus, in croton oil-induced rat pouch model, the subcutaneous accumulation of pouch tissue hydroxyproline over the course of 10 days is initially associated with a VA-positive myoFb phenotype and its transcription of TGF-β1, type I collagen and TIMP-1. Beyond day 10, a regression of pouch tissue collagen begins in association with the appearance of a VAD-positive myoFb phenotype and progressive increase in MMP-1 activity as the expression of TIMP-1 and TGF-β1are withdrawn. Regression of established fibrosis in failing organs may, therefore, be attainable through manipulation of myoFb phenotype and/or enhanced collagen degradation relative to collagen synthesis.

人工関節素材を用いた各種粉体による炎症反応に対するインドメタシンファルネシルの効果

In total joint replacement, particle induced inflammatory reactions cause periprosthetic bone resorption. Using an air pouch model in rats, we investigated the inflammatory reaction by alumina and polyethylene particles, and also investigated the anti-inflammatory effects of indometacin farnesil (IMF) . Irrigation fluid from the air pouch was collected and the total protein (TP) concentration and the prostaglandin E2 (PG E2) level were measured. To eliminate the effects of dilution, PG E2/TP was used. The pouch tissue was histologically evaluated. Without IMF, PG E2/TP was significantly higher by injecting alumina and polyethylene particles. In the polyethylene particles injected group, the level diminished with IMF 3 mg/kg/day, and was significantly lower with IMF 10 mg/kg/day. On the other hand, the level was not affected by IMF administration in the alumina particle injected group. A similar tendency was observed in the histology of pouch tissues. These results indicated that both alumina and polyethylene particles induced inflammatory reactions, however the anti-inflammatory effects of IMF depended on the characteristics of the particles.

Pouch Tissue and Angiotensin Peptide Generation

Myofibroblasts and their potential to generate angiotensin (Ang) II and transforming growth factor beta 1 (TGF-β1) at sites of infarction in the rat heart have been implicated in tissue repair. These cells likewise contribute to repair in a subcutaneous pouch model of fibrous tissue formation. Their appearance in pouch tissue coincides with high density ACE and Ang II receptor binding, suggesting a role for Ang II in tissue repair. Using pouch tissue studied at different time points of repair, the present study examined the expression of requisite mRNA for Ang peptide generation: angiotensinogen, Ao; an aspartyl protease, either cathepsin-D, Cat-D, or renin; and angiotensin converting enzyme, ACE. TGF-β1and type I collagen mRNA expression was also addressed. Unlike pouch studied on day 2 and 4, at 7, 14 and 21 days, we found: (a) expression of Ao, Cat-D but not renin, ACE and TGF-β1mRNA; (b) Ang I and Ang II peptides in pouch tissue and exudate; (c) the presence of Cat-D activity but no renin activity; (d) an increase in type I collagen mRNA with time; (e) upregulation of pouch tissue ACE mRNA expression by lisinopril treatment, whereas AT1and AT2receptor antagonists (losartan and PD 123177, respectively) downregulated the expression of mRNA for ACE, when compared to untreated controls; (f) downregulation of TGF-β1mRNA expression by lisinopril and losartan compared to untreated controls; and (g) PD 123177 had no effect, whereas lisinopril and losartan treatment significantly (P<0.05) reduced type I collagen mRNA expression. Thus, in this model of fibrous tissue formation, we found expression of component genes involved in Ang peptide (I and II) and TGF-β1generation and Ang II upregulation of TGF-β1expression, suggesting Ang II and/or TGF-β1may upregulate type I collagen expression during tissue repair. Pharmacologic intervention studies with lisinopril or losartan indicate Ang II plays a role in the reciprocal regulation of ACE mRNA expression, which modulates Ang II levels at sites of repair.

Inhibition of tissue repair by spironolactone: role of mineralocorticoids in fibrous tissue formation.

Mineralocorticoids have been implicated in promoting fibrous tissue formation in various organs. In the present study, we sought to address the potential contribution of mineralocorticoids to fibrous tissue formation using a skin pouch model which has proved valuable for the analysis of inflammatory and wound healing responses. Skin pouches were induced in rats by administration of a phorbol ester, croton oil (0.5 ml of a 1% solution). After 2 weeks, rats were killed and intact pouch tissue collected. Pouch weights of control and aldosterone-treated (0.75 microg/h via osmotic minipump) rats were similar (3.33 +/- 0.44 g vs. 3.70 +/- 0.28 g respectively). However, pouch weights were reduced by more than 50% in spironolactone-treated (25 mg/day powdered in food) animals (1.62 +/- 0.22 g and 1.27 +/- 0.23 g respectively in aldosterone and spironolactone alone groups). To ascertain the effects of different treatments on collagen accumulation, hydroxyproline concentration was measured. Compared with controls, hydroxyproline concentration was significantly reduced following spironolactone treatment (17.1 +/- 0.08 vs. 7.5 +/- 2.0 microg/mg dry wt, respectively, p < 0.01). This response to spironolactone was negated by coadministration of aldosterone (hydroxyproline concentration was 18.6 +/- 2.1 microg/mg dry wt). Following bilateral adrenalectomy, spironolactone reduced pouch weight and hydroxyproline concentration, which was not the case for adrenalectomy alone. Two week aldosterone administration in uninephrectomized rats on high salt diet was deemed ineffective in modulating pouch development (pouch wet wts were 3.48 +/- 0.4 g vs. 3.00 +/- 0.19 g in controls and aldosterone-treated rats, respectively). Mineralocorticoid receptor expression in pouch tissue was demonstrated by RT/PCR. Furthermore, NADP+-dependent 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity was detected in pouch tissue, together with lower levels of NAD+-dependent 11beta-HSD2. Spironolactone (p < 0.05) significantly reduced 11beta-HSD1 activity compared with controls. Thus, fibrous tissue possesses requisite components of MC action, and antagonism of mineralocorticoid receptors by spironolactone attenuates its formation. Pouch formation is under the influence of circulating MC and, we would like to propose, is also mediated through corticosteroids generated de novo at the site of tissue repair.

Studies on development of dosage forms for pediatric use (V) oral mucosal irritation study of gummi drugs in hamster cheek pouch.

In the present study we investigated irritation of the oral mucosa and the safety of gummi drugs containing acetaminophen (AAP). The oral mucosae of hamsters were macroscopically examined for any evidence of irritation after gummi drugs were inserted into the cheek pouch and left there for 1 h. The cheek pouch tissue was also macroscopically and microscopically examined 24 h after gummi drugs were withdrawn from the cheek pouch. As a result, no evidence of irritation was found macroscopically 1 h after insertion, or macroscopically and microscopically 24 h after the withdrawal of the gummi drugs or placebos as compared with negative controls (saline). Considering these results, the gummi drugs administered in the present study produced no irritation to the oral mucosa.

Studies of the activities of lysosomal enzymes in serum and buccal pouch tissue of hamsters during 7,12-dimethylbenz[a]anthracene-induced carcinogenesis.

Alterations in the activities of certain lysosomal enzymes such as beta-D-galactosidase, beta-D-glucosidase, beta-D-glucuronidase, alpha-L-fucosidase, N-acetyl-beta-D-glucosaminidase, cathepsins B and D were studied in serum and tissue homogenates of buccal mucosa of hamsters treated with 0.5%, 7,12-dimethylbenz[a]anthracene (DMBA) in liquid paraffin. Among the enzymes studied, the activities of beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase showed significant elevation both in serum and tissue homogenates fro papilloma onwards and the elevations were progressive with the development of carcinomas. The elevations in the activities of alpha-D-fucosidase and cathepsin D were found to be significant from papillomatous tissue onwards whereas in serum they showed higher activities only in carcinoma stages. The activities of beta-D-glucosidase, beta-D-glucuronidase and cathepsin B in both serum and in tissue homogenate were elevated markedly only in carcinoma stages. It is suggested that beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase may be used as diagnostic markers for premalignant and malignant lesions of oral mucosa.

The role of Hoxa-3 in mouse thymus and thyroid development.

Targeted disruption of Hoxa-3 results in a number of regionally restricted defects in tissues and structures derived from or patterned by mesenchymal neural crest. However, analysis of mutant embryos with injections of a carbocyanine dye or with molecular markers that label these cells indicates that neither the amount nor the migration patterns of this neural crest population are grossly affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic capacity of this neural crest cell population to differentiate and/or to induce proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa-3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is first evident as an expansion of mesenchymal neural crest in the posterior part of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1 expression is observed in these cells in the mutant embryos. As pax-1 mutant mice also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to maintain pax-1 expression in these cells and that the reduction of pax-1 expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid gland is formed from the fusion of two structures of separate embryonic origin, the thyroid diverticulum, which is formed from endodermal epithelium in the floor of the pharynx, and the ultimobranchial body, formed from mesenchymal neural crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are defective in mutant mice. Often a vesicle is observed in mutant mice that is exclusively composed of calcitonin-producing cells, suggesting the persistence of an ultimobranchial body. Both aspects of the thyroid phenotype show variable expressivity among mutant animals, even on the two sides of the same mutant animal. This variability suggests the presence of a compensating gene or genes, whose utilization is stochastic. A reasonable candidate for providing this compensatory function is the paralogous gene Hoxb-3.

Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors.

We have recently put forward the hypothesis that the dual inhibition of proinflammatory nitric oxide (NO) and prostaglandins (PG) may contribute to the antiinflammatory properties of nitric oxide synthase (NOS) inhibitors. This hypothesis was tested in the present study. A rapid inflammatory response characterized by edema, high levels of nitrites (NO2-, a breakdown product of NO), PG, and cellular infiltration into a fluid exudate was induced by the administration of carrageenan into the subcutaneous rat air pouch. The time course of the induction of inducible nitric oxide synthase (iNOS) protein in the pouch tissue was found to coincide with the production of NO2-. Dexamethasone inhibited both iNOS protein expression and NO2- synthesis in the fluid exudate (IC50 = 0.16 mg/kg). Oral administration of N-iminoethyl-L-lysine (L-NIL) or NG-nitro-L-arginine methyl ester (NO2Arg) not only blocked nitrite accumulation in the pouch fluid in a dose-dependent fashion but also attenuated the elevated release of PG. Finally, carrageenan administration produced a time-dependent increase in cellular infiltration into the pouch exudate that was inhibited by dexamethasone and NOS inhibitors. At early times, i.e., 6 h, the cellular infiltrate is composed primarily of neutrophils (98%). Pretreatment with colchicine reduced both neutrophil infiltration and leukotriene B4 accumulation in the air pouch by 98% but did not affect either NO2- or PG levels. In conclusion, the major findings of this paper are that (a) selective inhibitors of iNOS are clearly antiinflammatory agents by inhibiting not only NO but also PG and cellular infiltration and (b) that neutrophils are not responsible for high levels of NO and PG produced.

Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic.

We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX-2 mRNA and protein coincided with the production of PGs in the pouch tissue and cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to macrophages obtained from the fluid exudate as well as to the inner surface layer of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the stomach. Furthermore, NS-398, a selective COX-2 inhibitor, and indomethacin, a nonselective COX-1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the air pouch. In contrast, only indomethacin blocked gastric PG and, additionally, produced gastric lesions. These results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects (e.g., gastric ulcers) associated with the nonselective, COX-1-directed antiinflammatory drugs.

Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue

Exogenous administration of epidermal growth factor (EGF) enhances tumor growth of H2T, a hamster pancreatic cancer that is inoculated in the cheek pouch. The effect of endogenous EGF on tumor growth, however, is not known. The main source of EGF in the body is the submandibular glands. This study examined the influence of submandibular gland resection (SMx) on H2T tumor growth in the cheek pouch and compared it to the growth in SC tissue. Bilateral SMx or sham operation was performed on male Syrian golden hamsters. In 30 hamsters (n = 15 for each operation group), 5 x 10(4) and 5 x 10(5) H2T cells were inoculated in the bilateral cheek pouches and intrascapular SC tissue, respectively (Exp. 1). In another 30 hamsters (n = 15 for each operation group), 5 x 10(5) and 1 x 10(6) H2T cells were inoculated at the same sites (Exp. 2). Two longest perpendicular diameters of the tumor were measured once a week for 12 wk (Exp. 1) or 8 wk (Exp. 2), and the tumor area was calculated. The tumor area in the cheek pouch became significantly smaller in the SMx group than the sham-operated group after the 8th wk (Exp. 1) or the 7th wk (Exp. 2). On the other hand, the tumor area in the SC tissue did not show any difference between groups through the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue angiotensin I-converting enzyme activity in spontaneously hypertensive hamsters

The purpose of this study was to measure angiotensin I-converting activity in heart, kidney, lung and cheek pouch tissue homogenates of spontaneously hypertensive and normotensive hamsters. We also determined inhibitor sensitivity and the effects of chloride anion concentration on kidney angiotensin I-converting activity in these animals. We found no significant differences in angiotensin I-converting activity between hypertensive and normotensive hamsters in all tissues tested. Inhibitor sensitivity of kidney angiotensin I-converting activity with captopril and lisonopril was similar in both groups. Finally, kidney angiotensin I-converting activity increased significantly in both groups as chloride anion concentration in the assay buffer increased. Substituting chloride anion for citrate abrogated the increase in angiotensin I-converting enzyme activity.