Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: activation of CD8(+) cells, interferon-gamma recovery and reduction of lung injury

A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8(+) lung cell activation, interferon-gamma recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-alpha. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-gamma and to restrict the growth of bacilli.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There is still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) Underwent ascending aortic stenosis for 8 weeks (group AAS, n = 9). LV performance wits assessed by transthoracic echocardiography Under anesthesia. Myocardial function Was studied in isolated papillary muscle preparations during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, 11 = 9). LV weight-to-body weight ratio (C: 2.13 +/- 0.14 mg/g; AAS: 3.24 +/- 0.44) LV relative wall thickness (C: 0.18 +/- 0.02; AAS: 0.33 +/- 0.09), and LV fractional shortening (C: 54 +/- 5%; AAS: 70 +/- 8%) were increased in group AAS (P<0.05). Echocardio-graphic analysis also indicated a significant association (r = 0.74 P<0.001) between the percent fractional shortening index and LV relative wall thickness. The performance of AAS isolated In muscle revealed that active tension (C: 6.6 +/- 1.7 g/mm(2); AAS: 6.5 +/- 1.5 g/mm(2)) and maximum rate of tension development (C: 69 +/- 21 g/mm(2)/s AAS: 69 +/- 18 g/mm(2)/s) were not significantly different Front group C (P>0.05). In conclusion, compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance. The improved LV function might be due to the ventricular remodeling, characterized by an increased relative wall thickness.

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures

Low O-2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Pulmonary Disease in Hamsters Infected with Leptospira interrogans: Histopathologic Findings and Cytokine mRNA Expressions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

BODE Index and GOLD Staging as Predictors of 1-Year Exacerbation Risk in Chronic Obstructive Pulmonary Disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental Basis and New Insights for Cell Therapy in Chronic Obstructive Pulmonary Disease

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Low intensity laser therapy (LILT) in vivo acts on the neutrophils recruitment and chemokines/cytokines levels in a model of acute pulmonary inflammation induced by aerosol of lipopolysaccharide from Escherichia coli in rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Group A T-loop for differential moment mechanics: An implant study

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Non-linear analysis of reinforced concrete plates by the boundary element method and continuum damage mechanics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)