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1.
J Mol Med (Berl) ; 90(6): 637-47, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22246130

ABSTRACT

Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.


Subject(s)
Bleomycin , Lung Injury/chemically induced , Lung/drug effects , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/pharmacology , Animals , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Gene Deletion , Humans , Male , Mice , Mice, Knockout
2.
Int J Epidemiol ; 36(4): 866-72, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17698884

ABSTRACT

BACKGROUND: Chagas disease, transmitted domestically by triatomine bugs, is the most important vector-borne disease in Latin America. The association between triatomine infestation and housing characteristics was investigated based on a standardized survey in 41 971 houses in 15 Departments in Colombia. METHODS: Multivariate logistic regression was used to test for associations of two highly correlated infestation measures of infestation (householders reporting having seen triatomines inside the house, and sending triatomines to the survey team), with 15 household-level risk factors. Risks were measured relative to a reference category of houses with up to three inhabitants, area up to 50 m(2), unplastered adobe walls, thatch roof and no outbuildings or domestic animals. RESULTS: The probability of seeing triatomines was highest for households with over seven inhabitants (OR = 1.24, 95% CI 1.11-1.39), overhead storage space (OR = 1.16, 95% CI 1.03-1.32), grain shed (OR = 1.25, 95% CI 1.02-1.52), cats (OR = 1.27, 95% CI 1.14-1.42) and pigs (OR = 1.16, 95% CI 1.03-1.30). Lowest risks were in houses with wooden walls (OR = 0.46, 95% CI 0.34-0.61), fully plastered walls (OR = 0.78, 95% CI 0.68-0.88), roofs made of tiles (OR = 0.51, 95% CI 0.33-0.78) and flagstone floors (OR = 0.57, 95% CI 0.42-0.76). Results for householders returning triatomines support this set of risk factors, but with wider confidence intervals. CONCLUSIONS: Surveillance of a few easily assessed household characteristics provides an accurate, rapid assessment of house-level variation in risk. Measured effect sizes for specific structural characteristics could be used to maximize the cost-effectiveness of programmes to reduce vector infestation and interrupt Chagas disease transmission by improving house quality.


Subject(s)
Chagas Disease/transmission , Housing , Insect Vectors , Rhodnius , Animals , Animals, Domestic , Chagas Disease/prevention & control , Colombia , Ectoparasitic Infestations , Health Surveys , Housing, Animal , Humans , Multivariate Analysis , Odds Ratio , Probability , Risk Assessment/methods , Risk Factors
3.
Toxicon ; 41(1): 29-39, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12467659

ABSTRACT

A transmission electron-microscope study has been performed on larval and juvenile skin of the Central American arrow-frog Dendrobates auratus to investigate early secretory processes and maturational changes in the serous (poison) glands. Poison biosynthesis involves the endoplasmic reticulum (both smooth and rough types), as well as Golgi stacks which release early serous product as secretory vesicles (or pre-granules). These vesicles contain fine-grained material, along with single electron-opaque bodies, spheroidal in shape, that accompany the grained product throughout its post-Gogian, maturational change. The first steps of this process involve condensation and lead to the formation of secretory granules with a glomerular-like substructure, resulting from a thick, random aggregation of rods (secretory granule subunits). Advanced maturational activity causes the loss of peculiar granule substructure: the dense bodies split into fragments, whereas the thick glomerular arrangement becomes looser, until the secretory product changes into a dispersed material. This ultrastructural study revealed biosynthesis and maturation processes in close sequence, suggesting the poison of D. auratus contains proteins and/or peptides as well as lipophilic compounds. Molecules of both these classes are known to perform several roles relevant to survival strategies in extant anurans. Furthermore, the ephemeral granules with a glomerular-like substructure detected in tadpoles and froglets exhibit the complex patterns of mature poisons in adult specimens of other anurans: Hylidae and related families. This agrees with current trends in the taxonomy of these advanced frogs and underlines the pertinence of an ontogenetic approach in investigating anuran phylogenesis.


Subject(s)
Amphibians , Exocrine Glands/metabolism , Exocrine Glands/ultrastructure , Poisons/metabolism , Skin/metabolism , Skin/ultrastructure , Animals , Larva
4.
J Acoust Soc Am ; 108(4): 1938-40, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11051520

ABSTRACT

Sounds produced by Irrawaddy dolphins, Orcaella brevirostris, were recorded in coastal waters off northern Australia. They exhibit a varied repertoire, consisting of broadband clicks, pulsed sounds and whistles. Broad-band clicks, "creaks" and "buzz" sounds were recorded during foraging, while "squeaks" were recorded only during socializing. Both whistle types were recorded during foraging and socializing. The sounds produced by Irrawaddy dolphins do not resemble those of their nearest taxonomic relative, the killer whale, Orcinus orca. Pulsed sounds appear to resemble those produced by Sotalia and nonwhistling delphinids (e.g., Cephalorhynchus spp.). Irrawaddy dolphins exhibit a vocal repertoire that could reflect the acoustic specialization of this species to its environment.


Subject(s)
Animal Communication , Dolphins , Vocalization, Animal , Animals , Queensland , Sound Spectrography , Species Specificity
5.
Rev. chil. cir ; 42(4): 358-61, dic. 1990. tab
Article in Spanish | LILACS | ID: lil-96739

ABSTRACT

Se realiza en el perro ligadura del colédoco y derivación biliodigestiva con asa interpuesta de yeyuno. El objetivo central de la experiencia es lograr una dilatación significativa del colédoco, sin signos de colangitis. Este objetivo se logra con la observación de dilatación creciente del colédoco a los 3,6 y 9 meses, con ausencia de signos de colangitis. Esta técnica puede ser valedera para solucionar el grave problema del colédoco fino, lesionado por trauma y/o yatrogenia


Subject(s)
Dogs , Animals , Anastomosis, Surgical/methods , Biliary Tract/surgery , Duodenum/surgery , Jejunum/surgery
6.
Rev. chil. cir ; 42(1): 45-6, mar. 1990. tab
Article in Spanish | LILACS | ID: lil-84530

ABSTRACT

La prevalencia de colelitiasis en las autopsias estudiadas, es mayor en el grupo de pacientes cirróticos (29,6%) que en el grupo de no cirróticos (18,5%). La distribución por sexo de colelitiasis, es similar para ambos en el grupo de cirróticos (1:1), mientras que en el grupo de pacientes no cirróticos la relación es de 3:1, en favor de las mujeres. La frecuencia de coledocolitiasis y colecistitis aguda encontrada en los pacientes cirróticos, es menor que en la población en general. En el paciente cirrótico la colecistitis aguda es una complicación particularmente grave. La proporción de cálculos de bilirrubinato, fue mucho mayor que la de cálculos mixtos y de colesterol


Subject(s)
Adult , Middle Aged , Humans , Male , Female , Cholelithiasis/surgery , Liver Cirrhosis, Alcoholic
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