The lower esophageal sphincter (LES) is characterized by basal tone and appropriately timed neurogenic relaxation. The physiological mechanisms underlying these crucial LES functions remain poorly understood. The current studies were designed to characterize the electrophysiological properties and neural regulation of LES circular smooth muscle (CSM), and to determine whether interstitial cells of Cajal (ICC) play a role in neurotransmission. Conventional intracellular recordings were performed in CD1, nNOS knock-out, eNOS knock-out and W/Wv mutant mice. Mouse LES consists of “sling” and “clasp” smooth muscle, which were studied separately in CD1 mice. In subsequent studies of mutant mice and respective controls, only the clasp muscle was examined, Immunohistochemical c-Kit staining of ICC was performed in wild-type and W/Wv mutant mice that were first characterized electrophysiologically. The smooth muscle of the LES clasp and sling displayed unitary membrane potentials with a resting membrane potential (RMP) of ~ -43 mV. Spontaneous nifedipine-sensitive action potentials superimposed on the unitary potentials were usually recorded in the LES clasp, but not sling muscle. A monophasic inhibitory junction potential (IJP) was recorded in sling CSM, whereas a biphasic IJP consisting of an initial IJP, followed by long-lasting slow IJP (LSIJP) was recorded in clasp. Further pharmacological studies using control and various knockout mice suggest that: 1. the CSM of the mouse LES is innervated by cholinergic, nitrergic and purinergic nerves; 2. the LSIJP is mediated entirely by nitrergic nerves, whereas purinergic and nitrergic nerves produce the monophasic IJP in the LES sling and initial phase of biphasic IJP in the LES clasp; 3. Ca2+/CaM-kinase II is involved in the regulation of the nitrergic IJPs; 4. TREK-1 K+ channels are not involved in the nitrergic IJP; 5. purinergic and cholinergic neurotransmission is intact in LES CSM of W/Wv mutant mice, whereas nitrergic neurotransmission is impaired in about half of the animals. In animals in which nitrergic neurotransmission was intact, ICC-IM were markedly deficient immunohistologically, suggesting that ICC are not required for nitrergic neurotransmission; 6. impaired nitrergic neurotransmission in W/Wv mutant mice is associated with dysfunction of a Ca2+-dependent signaling cascade primed by spontaneous Ca2+ release from the sarcoplasmic reticulum. / Thesis (Ph.D, Physiology) -- Queen's University, 2008-01-24 15:54:52.175

The U.S. Army Medical Department (AMEDD) has used the interstitial building system (IBS) as a design component for some of the hospitals in its healthcare infrastructure portfolio. Department of Defense (DoD) leadership is aware of increases in healthcare costs and understands the importance of safely reducing costs, which may be possible through design initiatives. An analysis was performed on facility maintenance metrics for ten different U.S. Army hospitals, including IBS design and conventional / non-interstitial building system (NIBS) design. Statistical analysis indicated a significant difference in cost and time data between IBS and NIBS for most of the building systems considered (HVAC, electrical, plumbing, and interior). Scheduled maintenance for the plumbing building system was not found to have a significant difference in costs; scheduled maintenance for the HVAC and plumbing building system was not found to have a significant difference in time expended. The data in this study showed that facility maintenance cost and time were generally lower for IBS than NIBS. Time spent (and associated cost) for scheduled maintenance of the electrical and plumbing building systems were slightly higher in IBS, though not significantly higher for plumbing. It may be easier to reach the plumbing and electrical building systems due to the greater accessibility afforded by IBS design. While a cost premium is estimated for integrating IBS design, the savings provided by life cycle facility maintenance is estimated to be up to three and a half times the initial cost premium.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Techn. Universiẗat, Diss., 2004--Dresden.

Introdução: a cistite intersticial é doença crônica do trato urinário inferior cujos sintomas são: aumento da freqüência urinária, nictúria, dor pélvica ou perineal que piora com a repleção vesical e melhora com a micção. A etiopatogenia não é totalmente conhecida, mas há indícios de que os glicosaminoglicanos e proteoglicanos que revestem o urotélio vesical possam participar da sua gênese. A perda destes componentes protetores facilitaria o contato de íons e solutos presentes na urina com as porções mais profundas do urotélio desencadeando e perpetuando um processo inflamatório local. Para tentar entender seu metabolismo, investigamos o comportamento dos glicosaminoglicanos na urina e no tecido (biópsia do urotélio vesical) de pacientes portadoras de cistite intersticial e de incontinência urinária de esforço genuína. Casuística e métodos: o perfil e expressão gênica de glicosaminoglicanos no tecido, e o perfil dos glicosaminoglicanos da urina de 11 pacientes com cistite intersticial foram comparados aos de 11 pacientes com incontinência urinária de esforço. A análise estatística foi feita através de teste T e Anova, considerando significativos valores p<0,05. Resultados: verificamos que pacientes com cistite intersticial excretam menor concentração de glicosaminoglicanos na urina do que as portadoras de incontinência urinária de esforço (0,45 ± 0,11 x 0,62 ± 0,13 g/mg creatinina, p<0,05), porém sem redução do conteúdo de glicosaminoglicanos no urotélio. Na imunofluorescência o urotélio de pacientes com cistite intersticial mostrou maior marcação de TGF-beta, decorim (um proteoglicano de condroitim/dermatam sulfato), fibronectina e de ácido hialurônico. Foi identificada menor expressão gênica (PCR em tempo real) das sintases e uma hialuronidase do ácido hialurônico no urotélio das cistites intersticiais. Conclusão: a combinação desses resultados sugere que os glicosaminoglicanos podem estar relacionados ao processo contínuo de inflamação e remodelamento do urotélio disfuncional presente na cistite intersticial. O estudo da expressão gênica pode representar uma altenativa para o entendimento da doença. / Introduction: interstitial cystitis is a chronic disease of the lower urinary tract whose symptoms are: increased urinary frequency, nocturia, perineal or pelvic pain that worses with bladder filling and improves with urination. The pathogenesis is not fully known, but there is evidence that proteoglycans and glycosaminoglycans lining the bladder urothelium can participate in its genesis. The loss of these protective compounds facilitate the contact of ions and solutes in the urine with deeper portions of bladder wall triggering and perpetuating a local inflammatory process. We investigated GAG behavior in urine and tissue (biopsy of bladder urothelium) of patients with IC/PBS and genuine stress urinary incontinence (SUI) in an attempt to better understand its metabolism. Patients and Methods: gene expression and glycosaminoglycans profile in tissue, and glycosaminoglycans profile in urine of 11 patients with interstitial cystitis were compared to 11 patients with pure urinary stress incontinence. Statistical analysis were performed using t Student test and Anova, considering significant when p<0,05. Results: patients with interstitial cystitis excreted lower concentration of glycosaminoglycans in urine when compared to those with pure urinary stress incontinence (respectively 0.45 + 0.11 x 0.62 + 0.13 mg/mg creatinine, p< 0.05). However, there was no reduction of the content of glycosaminoglycans in the urothelium of both patients. The immunofluorescence study showed that patients with interstitial cystitis had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. We were able to indentify by real-time PCR lower gene expression of hyaluronic acid synthases and hyaluronidase in the urothelium of patients with interstitial cystitis. Conclusion: the results suggest that glycosaminoglycans may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the interstitial cystitis. The study of the gene expression may represent an alternative to understand the disease

As comunidades da fauna de copépodes de águas intersticiais da zona hiporrêica de um igarapé da Amazônia Central e de um rio da mata atlântica da região Sudeste do Brasil são comparadas quanto à composição, diversidade, e distribuição dos organismos. A relação das espécies identificadas com os fatores abióticos é analisada, com o objetivo de se estabelecer quais são os fatores determinantes para a distribuição das mesmas. Os fatores abióticos mensurados são: temperatura, pH, oxigênio dissolvido e granulometria do sedimento. Na areia grossa, há dominância de copepoditos e do gênero Forficatocaris (uma espécie para a mata atlântica e duas novas para a Amazônia). Essas três espécies e os copepoditos exploram o mesmo tipo de micro-hábitat no substrato. Quando a areia média é o substrato predominante, há o aumento na presença dos outros gêneros, como Potamocaris (uma espécie para a mata atlântica e uma nova espécie para a Amazônia) e Parastenocaris (mata atlântica), além do declínio no número de copepoditos. Há uma relação direta entre a temperatura e a distribuição dos microcrustáceos, ocorrendo o predomínio destes animais em temperaturas mais baixas. Há diferenças significativas dos valores de pH quando comparadas localidades distintas (Amazônia e mata atlântica); no entanto, quando comparadas as estações seca e chuvosa de um mesmo local, essa diferença não aparece. Sugere-se que o pH influencie na composição das espécies, e não em sua distribuição. Há um número similar de espécies ocupando os dois ambientes e um padrão de distribuição da fauna hiporrêica. Estas semelhanças apontam para a existência de padrões na estrutura e funcionamento destas comunidades naturais de microcrustáceos intersticiais, moldadas por pressões seletivas parecidas. / The assemblages of the copepod fauna from interstitial waters in the hyporheic zones from a stream in Central Amazon and a stream in the Atlantic rainforest of southeastern Brazil were compared in terms of composition, diversity and organism distribution. The relation of the identified species with abiotic factors was analyzed, aiming at establishing which factors were determinant for their distribution. The abiotic factors analyzed were: temperature, pH, dissolved oxygen, and sediment granulometry. In thick sand, there is predominance of copepodites and of the genus Forficatocaris (one species found in the Atlantic rainforest and two new species in the Amazon). These three species of Forficatocaris and the copepodites explore the same kind of microhabitat in the sediment. When medium size of sand grains prevail, there is an increase in the presence of other genera, such as Potamocaris (one species for the Atlantic rainforest and one new species for the Amazon) and Parastenocaris (Atlantic rainforest), besides a decline in number of copepodites. There is a direct ratio between the temperature and the distribution of microcrustaceans, with a predominance of these invertebrates in lower temperatures. There are significant differences in pH values when both localities (Amazon and Atlantic rainforest) are compared; however, comparisons between seasons (lower rainfall versus rainy periods) in a same location did not yield differences. It is suggested that the pH influences species composition, but not species distribution. There is a similar number of species inhabiting both environments and a distribution pattern for the hyporheic fauna. These similarities point at the existence of patterns in the structure and behavior in these natural communities of interstitial microcrustaceans, molded by similar selective pressures.

Abstract Antioxidants function as blockers of radical processes and eliminate harmful reactive oxygen species (ROS) produced during normal cellular metabolism. A complex antioxidant defence system has evolved to protect the cellular homeostasis. This system includes antioxidant enzymes (AOEs), such as superoxide dismutases (SODs), which are intracellular MnSOD and CuZnSOD and extracellular ECSOD, H2O2 scavenging enzymes catalase and glutathione peroxidase, and hemeoxygenase-1 (HO-1), an important enzyme in heme metabolism, which has also been suggested to have antioxidant capacities. ROS play an important role in the pathogenesis of interstitial lung diseases. These diseases represent a group of disorders with different etiology, histopathology, treatment and prognosis. Sarcoidosis, extrinsic allergic alveolitis and two different forms of idiopathic pulmonary fibrosis, usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) were included in this study. The purpose of this research was to evaluate the expressions of inducible nitric oxide synthase (i-NOS), endothelial nitric oxide synthase (e-NOS) and xanthine oxidase (XAO), oxidant generating enzymes commonly associated with tissue injury, and, on the other hand, the expressions of AOEs suggested to be involved in the defence of lung tissue against oxidant stress. The methods included immunohistochemistry on lung biopsies (n=48) and Western blotting, Northern blotting or reverse polymerase chain reaction (RT-PCR) on human inflammatory cells and cells obtained from bronchoalveolar lavage. I-NOS was intensively expressed in inflammatory, but not in fibrotic lesions, similar e-NOS expression was found in control lung and in all interstitial lung diseases, while XAO was mainly negative. MnSOD and HO-1 were highly expressed in the granulomas of sarcoidosis. In contrast the expressions of MnSOD and HO-1 in late fibrotic lesions of UIP were low or undetectable by immunohistochemistry. CuZnSOD and catalase showed similar immunoreactivity in healthy and diseased lung. A cell specific expression and regulation of various enzymes may play an important role during acute inflammatory diseases and also in the progression of lung fibrogenesis.

京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第19654号 / 薬博第824号 / 新制||薬||240(附属図書館) / 32690 / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 松原 和夫, 教授 中山 和久, 教授 金子 周司 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20252号 / 医博第4211号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 三森 経世, 教授 伊達 洋至, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM