RESUMO
The development of techniques for endoscopic resection has provided new strategies for radical conservative treatment of superficial esophageal neoplasms, even those that are circumferential, such as Barrett's neoplasia. However, it is necessary to prevent the formation of scar tissue that can be responsible for esophageal strictures following circumferential resection. Preliminary data have suggested the possible efficacy of a hemostatic powder in the promotion of wound healing. The study aims to assess the effectiveness of Hemospray (Cook Medical) in a swine model of post-endoscopic esophageal stricture. Our prospective controlled study included 21 pigs. A 6-cm circumferential submucosal dissection of the esophagus (CESD) was performed in each pig. Group 1 (n = 11) only underwent CESD and Group 2 (n = 10) had repeated Hemospray applications after CESD. Clinical, endoscopic, and radiological monitoring were performed, blood levels of four inflammatory or pro-fibrotic cytokines were assessed, and histological analysis was performed. Median esophageal diameter was greater in the group treated with Hemospray (2 mm [1-3] vs. 3 mm [2-4], P = 0.01), and the rate of symptomatic esophageal stricture was 100% and 60% in Groups 1 and 2, respectively (P = 0.09). The thicknesses of esophageal fibrosis and inflammatory cell infiltrate were significantly lower in Group 2 than in Group 1 (P = 0.002 and 0.0003, respectively). The length of the neoepithelium was greater in Group 2 than in Group 1 (P = 0.0004). Transforming growth factor-ß levels were significantly lower in Group 2 than in Group 1 (P = 0.01). The application of Hemospray after esophageal CESD reduces scar tissue formation and promotes reepithelialization, and therefore is a promising therapeutic approach in the prevention of post-endoscopic esophageal stricture.
Assuntos
Ressecção Endoscópica de Mucosa , Mucosa Esofágica/efeitos dos fármacos , Estenose Esofágica/prevenção & controle , Esofagoscopia , Hemostáticos/farmacologia , Minerais/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Reepitelização/efeitos dos fármacos , Animais , Esôfago de Barrett/cirurgia , Cicatriz/prevenção & controle , Mucosa Esofágica/cirurgia , Esôfago/efeitos dos fármacos , Esôfago/cirurgia , Estudos Prospectivos , SuínosRESUMO
An extrapolation chamber of type Böhm 23392, used for the dosimetry of RQR beam qualities at the Secondary Standard Dosimetry Laboratory of King Faisal Specialist Hospital, is presented. A computer-based motorized system consisting of a stepping motor coupled to the chamber's built-in micrometer screw was designed to expedite the measurements process, giving a linear relationship between the number of motor steps and the chamber depth with a Coefficient of Determination (COD) equal to 0.9990. The extrapolation chamber along with the motorized system was used to determine the extrapolation curves. The slope of the extrapolation curves, measured for the eight RQR beam qualities with a relative uncertainty between 0.17% and 0.58%, varies linearly with the beam quality expressed in terms of HVL, with a COD between 0.9995 and 1.0000.
RESUMO
One of the well-known consequences of established hypertension is an increase in connective tissue proteins in the walls of the large arterial blood vessels. Using renal clip and Dahl salt-sensitive rat models of systemic hypertension, we investigated the effect of developing hypertension on elastin production and accumulation in rat aorta. In both models of hypertension, increased accumulation of arterial elastin appeared coincidentally with, and was proportional to, elevation of blood pressure. In spite of large increases in absolute amounts of elastin, the proportion of elastin present in the vessel wall remained essentially constant from the earliest stage of the response. These changes in elastin synthesis and accumulation took place in the absence of evidence of cell proliferation. Treatment of Dahl rats with colchicine during development of hypertension affected blood pressure rise only marginally but abolished the vascular hypertrophic response. Our results suggest that the response of elastin production to increased blood pressure is rapid and sensitive, and that the stimulus for increased synthesis is an increase in wall stress. The striking effect of colchicine may indicate a role of elements of the cytoskeleton in the perception of stress by the vascular smooth muscle cells or in the transduction of that stress into increased production of connective tissue proteins.
Assuntos
Aorta/fisiopatologia , Colchicina/farmacologia , Elastina/biossíntese , Hipertensão Renal/fisiopatologia , Hipertensão/fisiopatologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , DNA/análise , Hipertensão/patologia , Hipertensão Renal/patologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Ratos , Ratos Endogâmicos , Valores de Referência , Fatores de TempoRESUMO
Multiple isoforms of tropoelastin, the soluble precursor of elastin, are the products of translation of splice-variant mRNAs derived from the single-copy tropoelastin gene. Previous data had demonstrated DNA sequence heterogeneity in three domains of rat tropoelastin mRNA, indicating alternative splicing of several exons of the rat tropoelastin gene. Rat tropoelastin genomic clones encompassing the sites of alternative splicing were isolated and sequenced. Two sites of alternative splicing identified in rat tropoelastin mRNA sequences corresponded to exons 13-15 and exon 33 of the rat tropoelastin gene. Furthermore, the variable inclusion of an alanine codon in exon 16 resulted from two functional acceptor sites separated by three nucleotides. DNA sequences flanking exons subject to alternative splicing were analyzed. These exons contained splicing signals that differed from consensus sequences and from splicing signals of constitutively spliced exons. Introns immediately 5' of exons 14 and 33, for example, lacked typical polypyrimidine tracts and had weak, overlapping branch point sequences. Further, a region of secondary structure encompassing the acceptor site of exon 13 may influence alternative splicing of this exon. These results demonstrate that multiple cis-acting sequence elements may contribute to alternative splicing of rat tropoelastin pre-mRNA.