Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.

Composição da matriz extracelular do ligamento cardinal de mulheres na pós-menopausa com e sem prolapso uterino / Composition of extracellular matrix of the cardinal ligament in postmenopausal women with and without uterine prolapse

O prolapso uterino tem sua incidência aumentada na pós-menopausa. O objetivo deste estudo é identificar as alterações na matriz extracelular do ligamento cardinal associadas à menopausa e ao prolapso uterino. Ligamento cardinal de três diferentes grupos de mulheres, pré-menopausa, prolapso uterino e pós-menopausa, foram identificados e biopsiados durante 57 histerectomias abdominais ou vaginais. As amostras foram processadas por métodos bioquímicos para caracterização e quantificação de glicosaminoglicanos sulfatados e colágeno. As concentrações relativas de glicosaminoglicanos foram obtidas por eletroforese. Procedimentos histológicos foram feitos para identificar fibras elásticas (Weigert), distribuição de colágeno (Picro Sirius) e decorin (imunohistoquímica). Nossos resultados mostraram aumento na concentração de GAG de 72,2%, redução na concentração de colágeno de 37% e diminuição de 22% de fibras elásticas no grupo de prolapso uterino quando comparado ao grupo da pós-menopausa (p<0,05, p<0,04 e p<0,05 respectivamente). As concentrações relativas de glicosaminoglicanos sulfatados para condroitin sulfato, heparan sulfato e dermatan sulfato não mostraram diferenças entre os três grupos. A organização do colágeno foi similar entre os três grupos e a marcação do decorin pareceu estar diminuída no grupo de prolapso uterino. Nossos resultados indicam alterações no metabolismo do tecido conjuntivo. O ligamento cardinal da mulher na pós-menopausa possui uma matriz extracelular mais densa. Esta alteração não ocorre na mulher com prolapso uterino.

Uterine prolapse has increase of incidence after menopause. The aim of this study was to identify the changes in extracellular matrix of cardinal ligaments associated to menopause and uterine prolapse. Cardinal ligament of 3 different groups (pre-menopause, menopause and uterine prolapse) are identified and biopsied during 57 women's abdominal or vaginal hysterectomy. Biopsy specimens were assessed by biochemical methods to characterize and quantify sulfated glycosaminoglycans and collagen. Relative concentrations of GAG were obtained by electrophoresis. Histological procedures are made to identify elastic fibers (Weigert) collagen distribution (Picro sirius) and decorin (immunohistochemistry). Our results showed increase in GAG concentration 72.2% in uterine prolapse group compared to menopause group (p<0.05). Collagen concentration was 37% lower in uterine prolapse group compared to menopause group (p<0.04). Relative concentration of GAG: heparan sulfate, chondroitin sulfate and dermatan sulfate showed no differences among three groups. Elastic fibers showed a significant reduction of aproximately 22% uterine prolapse group compared to menopause group (p<0.05). Collagen organization was similar in three groups and the staining pattern of decorin seemed to be decreased in uterine prolapse group. Our results indicate changes in connective tissue metabolism. Cardinal ligament in postmenopausal women has a denser extracellular matrix. This change is not observed in women with uterine prolapse.

Respiratory mechanics do not always mirror pulmonary histological changes in emphysema

OBJECTIVE: To verify the accordance of functional and morphometric parameters during the development of emphysema. METHODS: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days. Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed. To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma. RESULTS: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema. However, only the mean linear intercept values remained increased until the 40th day. The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day. The number of macrophages increased beginning on the 1st day. The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day. However, 8-isoprostane expression was only increased on the 1st and 3rd days. CONCLUSIONS: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics. Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process.

Alterações do tecido conjuntivo e músculo liso no pênis de coelhos diabéticos / Connective tissue and smooth muscle alterations in diabetic rabbit penis

Introdução: Embora a disfunção erétil seja um problema frequente em pacientes com diabete mellitus, poucos estudos avaliaram as alterações da estrutura peniana nesta condição. Objetivo: Avaliar a densidade volumétrica de colágeno, fibras do sistema elástico e células musculares lisas no corpo cavernoso (CC), corpo esponjoso (CE) e túnica albugínea (TA) no pênis de coelhos diabéticos. Método: Vinte seis coelhos Nova Zelândia foram utilizados. A diabete foi induzida em 13 coelhos com 8 semanas de idade com injeção intravenosa de 100 mg/kg de aloxano. 13 colehos normais serviram como controle. Após 10 semanas os animais foram mortos com overdose de thiopenthal sódico endovenoso. Os pênis foram dissecados retirando-se um fragmento da porção média sendo fixado em formol 10% tamponado (pH 7.3). Todo material foi processado para inclusão em parafina seguindo a técnica histológica de rotina. Principais medidas: A análise estereológica do colágeno, das fibras do sistema elástico e do músculo liso foi realizada em cortes de 5um no sistema teste M42. Os dados foram expressos em densidade volumétrica (Vv %). A organização de colágeno foi avaliada pela coloração do Picrosirius red sob polarização. Resultados: na túnica albugínea de coelhos diabéticos, houve um aumento de 88% da espessura (p<0.0003) com um acentuado turnover do colágeno. Além disso, o conteúdo de fibras elásticas foi 34% maior (p<0.0001). No CC dos coelhos diabéticos o colágeno diminuiu 45% (p<0.0001) com a presença de um colágeno mais organizado. As fibras do sistema elástico tiveram um decréscimo de 46% (p<0.0001). A diabete induziu um aumento de 11% de colágeno no CE (P<0.0235) com um acentuado turnover do colágeno. No CC de coelhos diabéticos houve um aumento de 40% de músculo liso (p<0.0001), enquanto no CE uma diminuição de 38% (p<0.0001). Conclusão: Os tecidos do pênis foram afetados de formas diferentes pela diabete, possivelmente devido à heterogeneidade celular...

Introdution: Although erectile dysfunction is a frequent problem in patients with diabetes mellitus, few studies have evaluated penile structure alteration in this condition. Aim: To assess the volumetric density of collagen, elastic system fibers and smooth muscles cells in the corpora cavernosa (CC), corpus spongiosum (CE) and tunica albuginea (TA) in the penis of diabetic rabbits. Methods: Twenty-six New Zealand white rabbits were used. Diabetes was induced at 8 weeks of age in 13 rabbits by intravenous injection of 100 mg/kg of alloxan. The remaining 13 rabbits served as a control group. After 10 weeks, the rabbits were killed using sodium thiopenthal. Mid-shaft fragments of the penis were obtained and processed by routine histological techniques. Main Outcome Measures: Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in 5-um sections by using a M42 System Test grid. Data were expressed as volumetric density (Vv - %). Collagen organization was evaluated by Picrosirius red staining under polarization. Results: In the TA of diabetic rabbits, thickness increased by 88% (p<0.0003) with an enhanced collagen turnover. Moreover, the elastic fiber content was 34% higher (p<0.0001). In the CC of diabetics, collagen was diminished by 45% (p<0.0001) with a more organized collagen. The elastic fibers were decreased by 46% (p<0.0001). Diabetes induced a 11% increase in CS collagen (p<0.0235) with an enhanced collagen turnover. Smooth muscle in the CC of diabetic rabbits was increased by 40% (p<0.0001), whereas in the CS it was decreased by a similar amount (p<0.0001). Conclusion: Penile tissues were affected differently by diabetes, possibly due to cellular heterogeneity. These changes could have an impact on blood flow and tissue resistance, and therefore, might adversely affect erection...

A comparative study of aging of the elastic fiber system of the diaphragm and the rectus abdominis muscles in rats

In the present study the age-related changes of the striated muscle elastic fiber system were investigated in the diaphragm and rectus abdominis muscles of 1-, 4-, 8- and 18-month-old rats. The activation patterns of these muscles differ in that the diaphragm is regularly mobilized tens of times every minute during the entire life of the animal whereas the rectus abdominis, although mobilized in respiration, is much less and more irregularly activated. The elastic fibers were stained by the Verhoeff technique for mature elastic fibers. Weigert stain was used to stain mature and elaunin elastic fibers, and Weigert-oxone to stain mature, elaunin and oxytalan elastic fibers. The density of mature and elaunin elastic fibers showed a progressive increase with age, whereas the amount of oxytalan elastic fibers decreased in both diaphragm and rectus abdominis muscles and their muscular fascias. These age-related quantitative and structural changes of the elastic fiber system may reduce the viscoelastic properties of the diaphragm and rectus abdominis muscles, which may compromise the transmission of tensile muscle strength to the tendons and may affect maximum total strength