RESUMEN
BACKGROUND: Expiratory central airway collapse is an increasingly recognized abnormality of the central airways and may be present in as many as 22% of patients evaluated for chronic obstructive pulmonary disease and/or asthma. Many current treatment options require invasive procedures that have been shown to cause significant morbidity and mortality. To test the hypothesis that Teflon injection will induce sufficient fibroblast proliferation and collagen deposition, we evaluated the time course on the effect of Teflon injection in the posterior membranous trachea on the histopathology of the tracheobronchial tree. METHODS: Six Yucatan Pigs were assigned to undergo general anesthesia and injection of 0.3 to 0.5 mL of sterile Teflon paste in 50% glycerin into the posterior membranous tracheal wall. A control pig received an equivalent volume of glycerin. Animals were euthanized in predefined intervals and tracheas were excised and examined under light microscopy for identifying fibroblast proliferation and collagen deposition. RESULTS: Compared with the control pig, the Teflon injection site showed tissue reaction of fibrohistiocytic proliferation and subsequent collagen deposition in all animals. Furthermore, the increased fibroblast proliferation and collagen deposition were time dependent (P<0.01). CONCLUSION: This pilot study demonstrates histopathologic changes in the trachea after Teflon injection, comprised of increased fibroblast activity and collagen deposition that could be of potential use in creating greater airway rigidity in patients with sever diffuse excessive dynamic airway collapse.
Asunto(s)
Colágeno/biosíntesis , Colágeno/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Politetrafluoroetileno/farmacología , Tráquea/efectos de los fármacos , Animales , Modelos Animales , Proyectos Piloto , Politetrafluoroetileno/administración & dosificación , PorcinosRESUMEN
We report 25 cases of skin neoplasm observed among 30 Long Evans rats serving as controls in a psychosocial behavioral study conducted in the Vivarium at Charles R. Drew University, Los Angeles, CA. The animals were 10 weeks old at the beginning of the study. All the skin tumors developed at 18 to 26 months of age and slowly enlarged over a period of 9 months. Multiple nodules occurred in 8 males and 6 females. None of the tumors regressed. The tumors were located around the hind leg and dorso-medial area and measured 1 to 2 cm. Physical examination revealed firm well demarcated dermal masses. Most of the tumor nodules were intradermal, and some had a central ulcerated or keratin-filled core. Microscopic examination performed on some of the tumors showed findings of classic Keratoacanthoma, whereas others showed histologic features suggestive of squamous cell carcinoma. These findings indicate a high rate (83%) of spontaneous skin neoplasms among aging Long Evans rats. To our knowledge, such a high rate of skin neoplasms in aged rodents has not been described in the literature. Furthermore, further studies should be undertaken to confirm these findings and to assess whether these rodents might serve as a model for studying the alterations in the immune system with aging.
Asunto(s)
Envejecimiento/patología , Carcinoma de Células Escamosas/patología , Queratoacantoma/patología , Neoplasias Cutáneas/patología , Envejecimiento/fisiología , Animales , Femenino , Masculino , Ratas , Ratas Long-EvansRESUMEN
A comparative study was performed to determine the effects of pH, osmolarity, and human urine on the transcription of several fim genes, as well as the overall expression of type 1 pili. Several fim-lacZYA fusions were constructed on single-copy plasmids to test a range of pHs and a range of osmolarities. Growth in acidic medium slightly reduced expression from all of the fim promoters (fimA, fimB, and fimE). Increased osmolarity in neutral-pH medium repressed fimA and fimB transcription by approximately 50% when 400 mM NaCl was used and nearly threefold when 800 mM NaCl was used, whereas fimE transcription rose slightly as the osmolarity increased. This effect was more pronounced in high-osmolarity acidic media; fimB and fimA expression decreased fivefold in growth media containing 800 mM NaCl compared to expression in growth media without added NaCl. Moreover, fimE expression doubled under the same high-osmolarity conditions compared to expression in a low-osmolarity acidic environment. When a fimB-lacZ or fimE-lacZ fusion was inserted into the chromosome of strain AAEC189, fimE expression changed slightly as the osmolarity increased, but fimB expression decreased by 50% in a low-pH high-osmolarity environment. When strain AAEC189 with either a plasmid-borne fimB-lacZ fusion or a plasmid-borne fimE-lacZ fusion was grown in human urine, similar changes in the levels of fimB and fimE expression were observed. Limiting-dilution reverse transcription-PCR confirmed that these changes in fim expression occurred in clinical isolates of uropathogenic Escherichia coli grown in media with different pHs and different osmolarities. Furthermore, the invertible switch region in uropathogenic strain NU149 shifted from favoring the phase-on position in a neutral-pH low-osmolarity environment to favoring the phase-off position in a low-pH high-osmolarity environment. Results obtained with an ompR mutant strain demonstrated that fimB expression was derepressed and that OmpR may neutralize repression by an acid response regulator of fimE expression in a low-pH environment. In addition, H-NS was verified to be important in regulation of fimB, but it had only a slight effect on fimE under the specific pH and osmotic growth conditions tested. Enzyme immunoassays with anti-type 1 pilus antibody and hemagglutination assays showed that fewer type 1 pili were detected with cells in a low-pH high-osmolarity environment. Together, these observations demonstrate that a combination of low pH and high osmolarity regulates the transcription of fim genes, which favors a shift in the invertible element to the phase-off orientation and a loss of type 1 pilus expression. Taken together, our data suggest that the environmental cues that we tested may regulate expression of type 1 pili in specific in vivo niches, such as murine kidneys and possibly human kidneys.