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1.
J Chem Phys ; 143(11): 114313, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26395711

RESUMO

Coupled cluster quantum chemical calculations of the potential energy surface and the induced dipole surface are reported for the He-Ar van der Waals collisional complex. Spectroscopic parameters are derived from global analytical fits while an accurate value for the long-range dipole coefficient D7 is obtained by perturbation methods. Collision-induced absorption spectra are computed quantum mechanically and compared with existing measurements.

2.
Zoolog Sci ; 29(7): 458-62, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22775255

RESUMO

Based on LM, TEM, and histochemical methods, the study describes the specific structure of subepidemal capillary loops in the integument of the hippopotamus (Hippopotamus amphibius). At 25- 60 µm, the diameter of the capillaries was more than twenty times larger than those found in other mammals, as was the diameter of the epidermal contact area of the hairpin turn, which had enlarged up to 200-400 µm(2). At about 13,400, the number of loops per cm(2) was three times higher than in the few other mammalian species measured to date. The remarkable sheath (thickness 2- 20 µm) of the capillary loops consists of a multitude of fine collagen IV fibres, which were in direct contact with the epidermal stratum (str.) basale, emphasizing an origin from the lamina fibroreticularis of the basement membrane. Additionally, the sheath contained many regions filled with free fatty acids. All observations confirmed the view that the walls of the subepidermal capillaries in the hippopotamus are adapted to withstand high blood pressure, permitting a high rate of blood vesselbased heat transfer from the periphery of the body. Until now this function is only known as an important thermoregulatory response in highly active mammals, e.g. dolphins. However, under hot climatic conditions but without strong exercise for cooling, such ability could be an effective and energy-saving procedure in semi-aquatic mammals.


Assuntos
Artiodáctilos/anatomia & histologia , Capilares/metabolismo , Capilares/ultraestrutura , Pele/irrigação sanguínea , Animais , Epiderme/ultraestrutura
3.
Exp Dermatol ; 19(4): 313-24, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20158518

RESUMO

Fish skin is a multi-purpose tissue that serves numerous vital functions including chemical and physical protection, sensory activity, behavioural purposes or hormone metabolism. Further, it is an important first-line defense system against pathogens, as fish are continuously exposed to multiple microbial challenges in their aquatic habitat. Fish skin excels in highly developed antimicrobial features, many of which have been preserved throughout evolution, and infection defense principles employed by piscine skin are still operative in human skin. This review argues that it is both rewarding and important for investigative dermatologists to revive their interest in fish skin biology, as it provides insights into numerous fundamental issues that are of major relevance to mammalian skin. The basic molecular insights provided by zebrafish in vivo-genomics for genetic, regeneration and melanoma research, the complex antimicrobial defense systems of fish skin and the molecular controls of melanocyte stem cells are just some of the fascinating examples that illustrate the multiple potential uses of fish skin models in investigative dermatology. We synthesize the essentials of fish skin biology and highlight selected aspects that are of particular comparative interest to basic and clinically applied human skin research.


Assuntos
Dermatologia , Peixes/fisiologia , Fenômenos Fisiológicos da Pele , Pele , Animais , Dermatologia/métodos , Peixes/microbiologia , Humanos , Modelos Animais , Pele/citologia , Pele/imunologia , Pele/microbiologia
4.
Zoolog Sci ; 27(10): 826-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20887181

RESUMO

The cuticle structure of the wool hairs (secondary hairs) of six otter species was examined by scanning electron microscopy to clarify the specific function of this hair type in the Lutrinae. The species studied were chosen according to the different genera, climatic regions, and degrees of association to water of the Lutrinae. Independent of their preferred habitats, the cuticle of every wool hair examined exhibited in all animals a rather similar shape and arrangement of the scales. This specific adaptive feature allows a flexible interlocking of adjacent wool hairs, which also helps to form thin wool hair bundles that surround small oval shaped spaces. Thus, the trapping of an effective insulating air layer is facilitated and heat loss from the body is reduced.


Assuntos
Cabelo/ultraestrutura , Lontras/anatomia & histologia , Animais , Feminino , Masculino , Microscopia Eletrônica de Varredura
5.
Exp Dermatol ; 17(7): 592-609, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18558994

RESUMO

Since the discovery of epithelial hair follicle stem cells (eHFSCs) in the bulge of human hair follicles (HFs) an important quest has started: to define useful markers. In the current study, we contribute to this by critically evaluating corresponding published immunoreactivity (IR) patterns, and by attempting to identify markers for the in situ identification of human eHFSCs and their niche. For this, human scalp skin cryosections of at least five different individuals were examined, employing standard immunohistology as well as increased sensitivity methods. Defined reference areas were compared by quantitative immunohistochemistry for the relative intensity of their specific IR. According to our experience, the most useful positive markers for human bulge cells turned out to be cytokeratin 15, cytokeratin 19 and CD200, but were not exclusive, while beta1 integrin and Lhx2 IR were not upregulated by human bulge keratinocytes. Absent IR for CD34, connexin43 and nestin on human bulge cells may be exploited as negative markers. alpha6 integrin, fibronectin, nidogen, fibrillin-1 and latent transforming growth factor (TGF)-beta-binding protein-1 were expressed throughout the connective tissue sheath of human HFs. On the other hand, tenascin-C was upregulated in the bulge and may thus constitute a component of the bulge stem cell niche of human HFs. These immunophenotyping results shed further light on the in situ expression patterns of claimed follicular 'stem cell markers' and suggest that not a single marker alone but only the use of a limited corresponding panel of positive and negative markers may offer a reasonable and pragmatic compromise for identifying human bulge stem cells in situ.


Assuntos
Células-Tronco Adultas/metabolismo , Biomarcadores/metabolismo , Folículo Piloso/metabolismo , Células-Tronco Adultas/citologia , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Conexina 43/metabolismo , Fibrilina-1 , Fibrilinas , Imunofluorescência/métodos , Folículo Piloso/anatomia & histologia , Folículo Piloso/citologia , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Proteínas de Filamentos Intermediários/metabolismo , Queratina-15/metabolismo , Queratina-19/metabolismo , Proteínas com Homeodomínio LIM , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Microscopia de Fluorescência , Proteínas do Tecido Nervoso/metabolismo , Nestina , Estatísticas não Paramétricas , Tenascina/metabolismo , Fatores de Transcrição/metabolismo
6.
Ann Anat ; 190(3): 264-76, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18489983

RESUMO

Based on sensitive light and electron microscopical lectin histochemistry, the distribution of saccharide residues is demonstrated in endothelial cells and/or the walls of integumental blood vessels of domesticated and wild mammals. In addition, the nomenclature of the blood vessel system in the skin is reviewed, and modified according to a generalized mammalian approach. Our comparative attempt demonstrated three (upper, mid-dermal, and dermal) plexus or retia in the integument of mammals of important systematic groups. The findings highlight a specific spectrum of terminal sugars in the endothelial cells and their glycocalyx and/or the blood vessel wall as related to the vessel retia and plexus present. The subepidermal blood vessel system, the capillary loops in particular, was marked by alpha-Man/alpha-Glc, alpha-D-GalNAc, beta-D-Gal/beta-D-GalNAc, and NANA-alpha(2,6)-GalNAc; the mid-dermal system by alpha-Man/alpha-Glc, and alpha-D-Gal/alpha-D-GalNAc; and the deep dermal system by alpha-Man/alpha-Glc, alpha-D-GalNAc, alpha-Gal, and beta-D-Gal/beta-D-GalNAc moieties. The results obtained are discussed from a comparative point of view, also with regard to certain basic functions of the endothelial cells and their glycocalyx.


Assuntos
Vasos Sanguíneos/citologia , Endotélio Vascular/citologia , Tegumento Comum/irrigação sanguínea , Lectinas/análise , Pele/irrigação sanguínea , Animais , Capilares/citologia , Gatos , Feminino , Glicocálix/ultraestrutura , Histocitoquímica , Mamíferos , Suínos
7.
Arch Dermatol Res ; 299(8): 393-7, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17639436

RESUMO

The present study revealed in detail the subcellular localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of beta-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.


Assuntos
Glândulas Apócrinas/imunologia , Muramidase/metabolismo , Escroto/imunologia , beta-Defensinas/metabolismo , Animais , Glândulas Apócrinas/metabolismo , Glândulas Apócrinas/ultraestrutura , Retículo Endoplasmático Rugoso/metabolismo , Retículo Endoplasmático Rugoso/ultraestrutura , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Cavalos , Imuno-Histoquímica , Masculino , Microscopia Imunoeletrônica , Escroto/metabolismo
8.
Cardiology ; 108(1): 28-34, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16960445

RESUMO

BACKGROUND: HMG-CoA reductase inhibitors (statins) are widely prescribed in patients with established systolic chronic heart failure (CHF). However, there is considerable controversy regarding their benefit in this setting. We therefore conducted a post-hoc analysis of outcomes according to statin use within the Second Cardiac Insufficiency Bisoprolol Study of the beta-blocker, bisoprolol, in NYHA classes III-IV systolic CHF patients (left ventricular ejection fraction <35%), receiving background ACE inhibitor and diuretics. METHODS: Analysis of clinical outcomes was performed according to baseline use of statins and subsequent randomisation to placebo or bisoprolol. Cumulative incidence curves for clinical events were constructed using the Kaplan-Meier method and tested for significance by log-rank statistic. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Two hundred and twenty-six of 2,647 patients were receiving statins at baseline (8.5%). Patients were well-matched in the 4 study groups at baseline for gender, weight, NYHA class and LVEF, however statin/bisoprolol patients were significantly younger (p < 0.05). Statin use at baseline was associated with a significant survival benefit compared with no statin use (p < 0.005, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.39-0.94). This benefit remained after adjusting for other significant predictors of survival (p < 0.05, HR = 0.60, 95%CI = 0.39-0.94). A significant interaction effect was noted with bisoprolol, survival being greatest in the statin/bisoprolol group (p < 0.001, HR = 0.14, 95% CI = 0.03-0.60). Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo group, 87.2% in the no statin/bisoprolol group and 82.8% in the no statin/placebo group. The statin/bisoprolol group was also associated with fewer cardiovascular (p < 0.005) and sudden deaths (p < 0.0005) compared with other groups. CONCLUSIONS: Despite the post-hoc, non-randomised nature of this analysis, these observations suggest that statin use appears to be beneficial in CHF. Furthermore, there appears to be a favourable interaction between statins and beta-blockade within the Second Cardiac Insufficiency Bisoprolol Study cohort. Prospective studies of statins are required to definitively address the role of these agents in established CHF.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Bisoprolol/administração & dosagem , Causas de Morte , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Análise de Variância , Distribuição de Qui-Quadrado , Doença Crônica , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Volume Sistólico , Análise de Sobrevida , Resultado do Tratamento
9.
Dis Aquat Organ ; 77(1): 17-27, 2007 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-17933394

RESUMO

Mucins are high molecular weight glycoproteins produced by goblet cells and secreted on mucosal surfaces. We investigated biochemical and histochemical properties of intestinal mucins of virus- and parasite-free common carp Cyprinus carpio in response to a single peroral application of endotoxin (lipopolysaccharide = LPS). Intracellular mucins were quantified histochemically by their carbohydrate content and characterized by specific, lectin-based methods. In addition, secreted epithelial (intracellular) and luminal (extracellular) mucins were isolated and separated by downward gel filtration. Carbohydrate and protein content were determined photometrically. Subsequently, terminal glycosylation was characterized by a lectin-binding assay. A peroral endotoxin application altered intestinal secretion and composition of intestinal mucin glycoproteins in common carp. A statistically significant decrease in mature luminal mucins was demonstrated, linked to a new biosynthesis of intracellular mucin glycoproteins. Simultaneous changes in the glycosylation pattern of isolated mucins were found. The intestinal mucosal system is purported to provide a removal mechanism for bacterial noxes by increasing secretion of mucins inducing a flushing-out effect, in combination with altered glycosylation patterns that change adhesion properties. Consequently, pseudofaeces of fish, which are a common sign of intestinal parasitical infections, may also be interpreted as an elimination mechanism for strong bacterial noxes.


Assuntos
Carpas/fisiologia , Glicoproteínas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Mucinas/efeitos dos fármacos , Administração Oral , Animais , Glicosilação/efeitos dos fármacos , Células Caliciformes/efeitos dos fármacos , Lectinas/análise , Lipopolissacarídeos/administração & dosagem , Organismos Livres de Patógenos Específicos , Fatores de Tempo
10.
Ann Anat ; 189(2): 143-56, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17419547

RESUMO

The results obtained from the outer ear skin of female pigs (German Landrace) by light microscopy (LM), transmission electron microscopy (TEM), and cryo scanning electron microscopy (cryo SEM) methods, in particular relying on careful and artefact-free tissue processing, exhibited that the stratum superficiale dermidis of the auricle had a very homogeneous and compact construction, especially in one area (central dorsum auriculae). Based upon the important measurements made [average thickness of stratum superficiale dermidis: 94 (+/-16) microm, region A: 81 (+/-10); average thickness of collagen fibre bundles: 12 (+/-2) microm, region A: 13 (+/-0.5); average density of subepidermal capillaries: 3134 (+/-459) loops/cm2, region A: 3497 (+/-247)], this impression was confirmed by low standard deviations for all parameters, in comparison to marginal locations studied. The capillary system present was analysed by LM and TEM for specific structural features, whereby it generally compared to the microvasculature in human skin. Moreover, a regular pattern of diffusion-relevant punctiform contacts of the capillary loop apex with the epidermal basement membrane became obvious. Cryo SEM, particularly offering the advantages of dispensation of chemical fixation, dehydration and solvents during processing, highlighted delicate structures without shrinkage and without loss of soluble sample components. Thus rather real spatial conditions in the region of the epidermo-dermal junction and the upper dermis were visualized, whereby very regular arrangements of the structures present became obvious. This pertained also to a correct demonstration of all components of the epidermal basement membrane, in particular the lamina lucida. In addition, the water-based stable character of the entire stratum superficiale dermidis could be emphasized as a basic feature for controlled diffusion processes.


Assuntos
Células Epidérmicas , Animais , Capilares/citologia , Capilares/ultraestrutura , Microscopia Crioeletrônica , Epiderme/ultraestrutura , Humanos , Modelos Animais , Pele/irrigação sanguínea , Suínos
11.
Circulation ; 112(16): 2487-95, 2005 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-16216962

RESUMO

BACKGROUND: Although many studies suggested direct vasomotor effects of hydrogen peroxide (H2O2) in vitro, little is known about the vasomotor effects of H2O2 in vivo. METHODS AND RESULTS: We have generated mice overexpressing human catalase driven by the Tie-2 promoter to specifically target this transgene to the vascular tissue. Vessels of these mice (cat++) expressed significantly higher levels of catalase mRNA, protein, and activity. The overexpression was selective for vascular tissue, as evidenced by immunohistochemistry in specimens of aorta, heart, lung, and kidney. Quantification of reactive oxygen species by fluorescence signals in cat++ versus catalase-negative (catn) mice showed a strong decrease in aortic endothelium and left ventricular myocardium but not in leukocytes. Awake male cat++ at 3 to 4 months of age had a significantly lower systolic blood pressure (sBP, 102.7+/-2.2 mm Hg, n=10) compared with their transgene-negative littermates (catn, 115.6+/-2.5 mm Hg, P=0.0211) and C57BL/6 mice (118.4+/-3.06 mm Hg, n=6). Treatment with the catalase inhibitor aminotriazole increased sBP of cat++ to 117.3+/-4.3 mm Hg (P=0.0345), while having no effect in catn (118.4+/-2.4 mm Hg, n=4, P>0.05). In contrast, treatment with the NO-synthase inhibitor nitro-L-arginine methyl ester (100 mg.kg BW(-1).d(-1)) increased sBP in cat++ and C57Bl/6 to a similar extent. Likewise, phosphorylation of vasodilator-stimulated phosphoprotein in skeletal muscle, left ventricular myocardium, and lung was identical in cat++ and catn. Endothelium- and NO-dependent aortic vasodilations were unchanged in cat++. Aortic KCl contractions were significantly lower in cat++ and exogenous H2O2 (10 micromol/L)-induced vasoconstriction. CONCLUSIONS: These data suggest that endogenous H2O2 may act as a vasoconstrictor in resistance vessels and contribute to the regulation of blood pressure.


Assuntos
Arteríolas/fisiologia , Peróxido de Hidrogênio/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Aorta Torácica/fisiologia , Arteríolas/efeitos dos fármacos , Catalase/genética , Catalase/metabolismo , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/metabolismo , Vasodilatação
12.
Cardiovasc Res ; 65(1): 254-62, 2005 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-15621054

RESUMO

OBJECTIVE: Recent studies from our groups have indicated that endothelial nitric oxide synthase (eNOS) expression is increased in cell culture by both shear stress and by hydrogen peroxide (H(2)O(2)). In vivo, exercise training, known to increase both endothelial shear stress and oxidative stress, also increases eNOS expression. It is unclear if H(2)O(2) contributes to an increase in eNOS expression in response to exercise training. METHODS: To address this question, we generated mice overexpressing human catalase (hCat) driven by the murine Tie-2 promoter to specifically target this transgene to the endothelium (cat(++)). RESULTS: Vessels of cat(++) expressed significantly higher levels of catalase mRNA and catalase protein and activity but normal levels of eNOS. Exercise alone had no effect on catalase expression in C57BL/6. Wild-type littermates of cat(++) showed an increase in eNOS expression with 3 weeks of exercise (2.53+/-0.42-fold) comparable to C57BL/6 (2.93+/-0.45-fold). In striking contrast, 3 weeks of exercise had no effect on aortic (1.33+/-0.32-fold) and myocardial (1.1+/-0.2-fold) eNOS expression in catalase transgenic mice. CONCLUSIONS: These data suggest that endogenous H(2)O(2) plays a key role in the endothelial adaptation to exercise training by stimulating an up-regulation of eNOS.


Assuntos
Catalase/metabolismo , Endotélio Vascular/metabolismo , Exercício Físico/fisiologia , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico Sintase/metabolismo , Amitrol (Herbicida)/farmacologia , Animais , Catalase/análise , Catalase/genética , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Engenharia Genética , Humanos , Peróxido de Hidrogênio/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Regiões Promotoras Genéticas , Receptor TIE-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Circulation ; 105(7): 855-60, 2002 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-11854127

RESUMO

BACKGROUND: Vasorelaxation to endothelial NO is mediated by activation of soluble guanylyl cyclase (sGC) and impaired by hypercholesterolemia in animals and humans. We investigated whether hypercholesterolemia impacts expression and function of sGC. METHODS AND RESULTS: White New Zealand rabbits (n=10 per group) received a standard diet for 16 weeks (SD16) (n=20) or 32 weeks (SD32) and a cholesterol diet (7.5 g/kg) for 16 weeks (CD16) (n=20) or 32 weeks (CD32), respectively. Another group received cholesterol diet for 16 weeks followed by standard diet for 16 weeks (CD/SD). Aortic expression of the alpha1-subunit of sGC (sGC-alpha1) and beta1-subunit of sGC (sGC-beta1) was assessed by Western blot. Function was measured by aortic relaxation to S-Nitroso-N-acetyl-D, L-penicillamine (SNAP) and sGC activity in aortic cytosols. Hypercholesterolemia induced an upregulation of sGC-beta1 in CD16 (3.5+/-0.4-fold, P<0.001 versus SD16) and CD32 (4.0+/-0.4-fold, P<0.001 versus SD32). A similar increase was found for sGC-alpha1. In striking contrast, basal and NO-stimulated sGC activities in aortic cytosols of CD16 were only slightly enhanced (1.4-fold, P<0.05). Furthermore, the vasodilator potency of SNAP (EC50 in -logM) was 10-fold lower in CD16 (6.76a+/-0.09) than in SD16 (7.66+/-0.14, P<0.01). The increase of sGC expression was completely reversible, as indicated by comparable sGC-beta1 amounts in SD32 and CD/SD (1.2+/-0.1-fold, P>0.05). Immunohistochemical analysis suggests that a great portion of the overexpressed sGC is located in intimal lesions. Additional experiments showed that increased vascular superoxide production induced by 6-anilino-5,8-quinolinedione (LY85385) reduces sGC-activity but increases sGC-expression. CONCLUSIONS: These results suggest that hypercholesterolemia induces a reversible overexpression of a dysfunctional vascular sGC, which may contribute to the pathogenesis of atherosclerosis.


Assuntos
Aorta/fisiopatologia , Hipercolesterolemia/enzimologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Aminoquinolinas/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Arteriosclerose/etiologia , Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Colesterol/sangue , Dieta Aterogênica , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase , Hipercolesterolemia/patologia , Técnicas In Vitro , Masculino , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Coelhos , Ratos , Ratos Wistar , Transdução de Sinais , Guanilil Ciclase Solúvel , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Regulação para Cima , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
14.
J Am Coll Cardiol ; 44(3): 624-31, 2004 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-15358031

RESUMO

OBJECTIVES: We sought to determine if the nitric oxide (NO) donor isosorbide mononitrate (ISMN) (200 mg/kg body weight/day) decreases vascular bioavailability of superoxide in atherosclerosis. BACKGROUND: Vascular oxidative stress limits the bioavailability of endothelial NO and promotes atherosclerosis, while NO itself exerts antioxidative effects. It is unknown if therapeutic NO impacts on vascular oxidative stress in atherosclerosis. METHODS: New Zealand white rabbits (n = 10 each group) were fed either normal chow (control), cholesterol chow (CHOL) (0.75%), or cholesterol chow enriched with ISMN (CHOL-ISMN). Rabbits were fed twice daily. After 16 weeks we used aortic segments to measure vascular superoxide (5-microM lucigenin), intimal lesion formation, and vasoreactivity to acetylcholine (ACH) and ISMN. RESULTS: Plasma cholesterol increased by 40-fold in CHOL and CHOL-ISMN. The plasma concentration of ISMN in CHOL-ISMN was 1,529 +/- 447 ng/ml. Superoxide formation (control: 228 +/- 20 counts/20 min/mg) was strongly enhanced in CHOL (345 +/- 46 counts/20 min/mg, p = 0.02) but not in CHOL-ISMN (229 +/- 23 counts/20 min/mg) demonstrating antioxidative effects of eccentric ISMN in vivo. In parallel, intima-media thickness of thoracic aorta (159 +/- 4 microm in control) was reduced from 645 +/- 41 microm (CHOL) to 440 +/- 51 microm (CHOL-ISMN, p < 0.05). Likewise, eccentric ISMN partially restored vascular responses to the NO donor S-nitroso-N-acetyl-D,L-penicillamine and improved endothelium-dependent vasorelaxation. The maximal ACH relaxation increased from 26.3 +/- 9.6% in CHOL to 49.7 +/- 8.1% in CHOL-ISMN; ISMN treatment induced a moderate nitrate tolerance as evidenced by diminished ISMN-induced vasodilation. CONCLUSIONS: These data suggest that eccentric ISMN can completely inhibit the increase of vascular bioavailability of superoxide and partially prevent intimal lesion formation and endothelial dysfunction in hypercholesterolemia.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Dinitrato de Isossorbida/análogos & derivados , Dinitrato de Isossorbida/farmacologia , Doadores de Óxido Nítrico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Superóxidos/sangue , Animais , Antioxidantes/farmacologia , Aorta Torácica/patologia , Disponibilidade Biológica , Colesterol/administração & dosagem , Colesterol/sangue , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Hipercolesterolemia/sangue , Hipercolesterolemia/patologia , Dinitrato de Isossorbida/administração & dosagem , Doadores de Óxido Nítrico/administração & dosagem , Coelhos , Túnica Íntima/patologia , Túnica Média/patologia
15.
J Am Coll Cardiol ; 41(11): 1994-2000, 2003 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-12798571

RESUMO

OBJECTIVES: We sought to investigate the effects of orally administered, long-term, eccentric isosorbide mononitrate (ISMN) on endothelial function. BACKGROUND: Previous studies have shown that nitrate tolerance induced by continuous transdermal glyceryl trinitrate (GTN) is associated with increased vascular superoxide production and endothelial dysfunction. In contrast, it is unclear whether vascular superoxide increases during eccentric administration of oral nitrates, which is a widely used therapeutic dosing regimen. METHODS: New Zealand White rabbits were randomly classified into three groups (n = 10, each) that received either placebo, ISMN at 2 mg/kg body weight per day (ISMN-2), or ISMN at 200 mg/kg body weight per day (ISMN-200) in an eccentric, twice-daily scheme for four months. Animals were sacrificed 3 h after application of the last ISMN dose. RESULTS: The continuously present, lowest ISMN plasma levels (ng/ml) were 4.8 +/- 0.2 in ISMN-2 and 14.5 +/- 4 in ISMN-200 (p = 0.026). Treatment with ISMN had no effect on aortic reactivity to phenylephrine, acetylcholine, or the nitric oxide (NO) donor S-nitroso-N-acetyl-D,L-penicillamine, while the half-maximal effective concentration of ISMN (EC(50)-value in -logM) was shifted from 5.23 +/- 0.03 (placebo) to 4.69 +/- 0.04 (ISMN-200) (p < 0.0001 by analysis of variance). This moderate in vivo nitrate tolerance was not associated with increased aortic superoxide production (5 micromol/l lucigenin). The cumulative (20-min) lucigenin signals (cpm/mg) were 211 +/- 34 (ISMN-200) and 230 +/- 22 (placebo) (p = 0.415). CONCLUSIONS: Long-term treatment with high-dose, eccentric ISMN does not increase vascular superoxide production and/or impair endothelium-dependent vasorelaxation, despite the development of moderate nitrate tolerance. Thus, it is unlikely that long-term anti-ischemic treatment with ISMN aggravates endothelial dysfunction in coronary artery disease.


Assuntos
Tolerância a Medicamentos/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Dinitrato de Isossorbida/análogos & derivados , Dinitrato de Isossorbida/administração & dosagem , Doadores de Óxido Nítrico/administração & dosagem , Vasodilatadores/administração & dosagem , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Dinitrato de Isossorbida/sangue , Modelos Cardiovasculares , Doadores de Óxido Nítrico/sangue , Fenilefrina/farmacologia , Coelhos , S-Nitroso-N-Acetilpenicilamina/farmacologia , Estatística como Assunto , Superóxidos/metabolismo , Tempo , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/sangue
16.
Arch Dermatol Res ; 296(10): 482-8, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15756567

RESUMO

The eccrine nasolabial glands were found in the hypodermis of the nasal plane in the North American raccoon (Procyon lotor). In addition to light and electron microscopic observations, the distribution and selectivity of complex glycoconjugates in the eccrine tubular glands of the raccoon snout skin were studied using various histochemical methods, particularly lectin staining. The secretory epithelium and the luminal secretions exhibited high amounts of glycoconjugates with various saccharide residues (alpha-D: -mannose, alpha-L: -fucose, beta-D: -galactose, beta-N-acetyl-D: -glucosamine, sialic acid). The excretory duct cells also showed positive reactions with most of the histochemical methods applied. The results are discussed with regard to possible functions of the glandular secretions. The complex glycoconjugates that are produced by the eccrine nasolabial glands may be related to moistening of the skin surface as well as protecting the epidermis against physical damage or microbial contamination. This is the first report on the glands in the snout skin of carnivores.


Assuntos
Glândulas Écrinas/anatomia & histologia , Glândulas Écrinas/fisiologia , Glicoconjugados/fisiologia , Guaxinins/anatomia & histologia , Guaxinins/fisiologia , Animais , Glândulas Écrinas/química , Glicoconjugados/análise , Histocitoquímica
17.
Acta Histochem ; 107(3): 187-98, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15893809

RESUMO

The localization of complex glycoconjugates in the nasolabial glands of the Japanese deer (C. nippon yakushimae) was studied using various histochemical methods, including lectin histochemistry, viewed using both light and electron microscopy. The secretory epithelium and luminal secretion of the deer nasolabial glands exhibited neutral and acidic glycoconjugates with different saccharide residues (alpha-D-mannose, alpha-N-acetyl-D-galactosamine, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid). Additionally, O-acetylated sialic acids were detectable in the glandular acini. The results obtained are discussed with regard to the specific functions of the glandular secretion, which may particularly improve water retention on the skin surface and protect against physical damage as well as microbial contamination. Furthermore, our results support the view of a salivary nature of this gland type.


Assuntos
Cervos , Glândulas Écrinas/química , Glicoconjugados/análise , Técnicas Imunoenzimáticas/métodos , Lábio , Nariz , Glândulas Salivares/química , Animais , Biomarcadores/análise , Estruturas Citoplasmáticas/ultraestrutura , Glândulas Écrinas/citologia , Glicoconjugados/química , Lectinas , Masculino , Microscopia Eletrônica de Transmissão , Glândulas Salivares/citologia
18.
Eur J Morphol ; 42(3): 127-34, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16393749

RESUMO

The distribution of complex glycoconjugates and antimicrobial substances in the ceruminous glands of the horse (Equus przewalskii f. dom., type: pony) was studied using carbohydrate histochemical and immunohistochemical methods. The epithelial cells and luminal secretion of these glands exhibited considerable amounts of glycoconjugates with various saccharide residues, such as alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid, including O-acetylated sialic acid. Several sugars (alpha-D-mannose, alpha-L-fucose, and beta-D-galactose) were also detectable in the secretion of sebaceous glands present. Additionally, lysozyme and the peptide group of beta-defensins are demonstrated as products of the apocrine ceruminous glands and sebaceous glands. The results obtained are discussed with regard to the functional significance of the glandular secretions. It is suggested that the complex carbohydrates, lysozyme and beta-defensins found in the ceruminous gland secretions are involved in the function of cerumen as a general antimicrobial protective agent in the external auditory canal.


Assuntos
Glândulas Apócrinas/metabolismo , Defensinas/metabolismo , Glicoconjugados/biossíntese , Cavalos/metabolismo , Muramidase/metabolismo , Animais , Glândulas Apócrinas/citologia , Sequência de Carboidratos , Cerume/química , Meato Acústico Externo/anatomia & histologia , Meato Acústico Externo/metabolismo , Glicoconjugados/química , Ligação Proteica
19.
Arch Dermatol Res ; 296(1): 12-20, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15083309

RESUMO

The localization and chemical nature of complex carbohydrates in the ceruminous glands of the Japanese miniature (Shiba) goat were studied using light and electron microscopic histochemical methods, particularly lectin histochemistry. The epithelial cells and luminal secretion of the caprine ceruminous glands contained large amounts of neutral and smaller amounts of acidic glycoconjugates with different terminal sugars (alpha- d-mannose, alpha-L-fucose, alpha-N-acetyl-D-galactosamine, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid). Several sugars (alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid) were also detectable in the secretion of the sebaceous glands. The results obtained are discussed with regard to the specific function of the glandular secretion mixture. The complex glycoconjugates found in the ceruminous gland secretion may control viscoelasticity of and bacterial proliferation within the cerumen in order to protect the external auditory canal against physical damage or microbial attacks.


Assuntos
Glândulas Apócrinas/metabolismo , Metabolismo dos Carboidratos , Cerume/metabolismo , Orelha Externa , Cabras/metabolismo , Animais , Glândulas Apócrinas/ultraestrutura , Glicoconjugados/química , Glicoconjugados/metabolismo , Histocitoquímica , Masculino , Microscopia Eletrônica
20.
Ann Anat ; 185(3): 223-31, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12801086

RESUMO

The distribution and selectivities of glycoconjugates in the ceruminous glands of the North American raccoon (Procyon lotor) were studied by light and electron microscopic histochemical methods, particularly lectin histochemistry. In the modified apocrine glands present, the apocrine secretion mode was combined with exocytosis, whereby the secretory epithelium and the luminal secretion of the ceruminous glands exhibited considerable amounts of complex carbohydrates with various terminal sugars (alpha-D-mannose, beta-D-galactose, alpha-L-fucose, alpha-N-acetyl-galactosamine, beta-N-acetyl-D-glucosamine, N-acetyl-neuraminic acid). Alpha-L-fucose and N-acetyl-neuraminic acid were distinctly prominent in secretory granules or within the free surface coat of the plasma membrane of the glandular cells, as well as in the luminal secretion. Several free sugars (alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine) were also detectable in the secretion of associated sebaceous glands. The ceruminous gland secretion may control viscoelasticity and/or bacterial degradation of the glandular secretion mixture to improve the protection of the external auditory canal against physical damage or microbial contamination.


Assuntos
Glândulas Apócrinas/citologia , Glicoconjugados/análise , Guaxinins/anatomia & histologia , Animais , Glândulas Apócrinas/metabolismo , Glândulas Apócrinas/ultraestrutura , Dissacarídeos/análise , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Complexo de Golgi/ultraestrutura , Hexoses/análise , Técnicas Histológicas/métodos , Lisossomos/ultraestrutura , Masculino , Microscopia Eletrônica , Microvilosidades/ultraestrutura , Glândulas Sebáceas/citologia , Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/ultraestrutura , Vesículas Secretórias/ultraestrutura
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