Anti-inflammatory and antinociceptive effects of phonophoresis in animal models: a randomized experimental study.

The aim of this study was to evaluate the therapeutic effects of ultrasound (US)-mediated phonophoresis alone or in association with diclofenac diethylammonium (DCF) administered topically in animal models of inflammation. A pre-clinical, prospective, and randomized experimental study of quantitative and qualitative nature was carried out. Phonophoresis was performed using a therapeutic ultrasound apparatus in two distinct models of acute inflammation. Edema was induced by an intraplantar injection of carrageenan and measured by plethysmography. The Hargreaves test was used to evaluate the antinociceptive activity and investigate the action of phonophoresis on tumor necrosis factor (TNF)-α production. A histological analysis with hematoxylin-eosin was used to evaluate tissue repair, and the expression of COX-2 was determined by immunohistochemical analysis. At the peak of inflammatory activity (3 h), treatment with US, US+DCF, and DCF significantly reduced edema formation compared to the control group. Treatment with US+DCF was more effective than treatment with US alone at both analyzed times. In the analysis of the antinociceptive activity, the treatments significantly increased the latency time in response to the thermal stimulus. Histopathological analysis revealed a reduction of the inflammatory infiltrates and immunohistochemistry demonstrated that the association was effective in reducing COX-2 expression compared to the control group. The association of DCF with US produced anti-inflammatory and antinociceptive effects in rat models of inflammation, which may be associated with inhibition of COX-2 and TNF-α production.

Anti-inflammatory and antinociceptive effects of phonophoresis in animal models: a randomized experimental study

The aim of this study was to evaluate the therapeutic effects of ultrasound (US)-mediated phonophoresis alone or in association with diclofenac diethylammonium (DCF) administered topically in animal models of inflammation. A pre-clinical, prospective, and randomized experimental study of quantitative and qualitative nature was carried out. Phonophoresis was performed using a therapeutic ultrasound apparatus in two distinct models of acute inflammation. Edema was induced by an intraplantar injection of carrageenan and measured by plethysmography. The Hargreaves test was used to evaluate the antinociceptive activity and investigate the action of phonophoresis on tumor necrosis factor (TNF)-α production. A histological analysis with hematoxylin-eosin was used to evaluate tissue repair, and the expression of COX-2 was determined by immunohistochemical analysis. At the peak of inflammatory activity (3 h), treatment with US, US+DCF, and DCF significantly reduced edema formation compared to the control group. Treatment with US+DCF was more effective than treatment with US alone at both analyzed times. In the analysis of the antinociceptive activity, the treatments significantly increased the latency time in response to the thermal stimulus. Histopathological analysis revealed a reduction of the inflammatory infiltrates and immunohistochemistry demonstrated that the association was effective in reducing COX-2 expression compared to the control group. The association of DCF with US produced anti-inflammatory and antinociceptive effects in rat models of inflammation, which may be associated with inhibition of COX-2 and TNF-α production.

Neuronal nitric oxide synthase-derived hydrogen peroxide is a major endothelium-dependent relaxing factor.

Endothelium-dependent vasorelaxation in large vessels is mainly attributed to Nomega-nitro-L-arginine methyl ester (L-NAME)-sensitive endothelial nitric oxide (NO) synthase (eNOS)-derived NO production. Endothelium-derived hyperpolarizing factor (EDHF) is the component of endothelium-dependent relaxations that resists full blockade of NO synthases (NOS) and cyclooxygenases. H2O2 has been proposed as an EDHF in resistance vessels. In this work we propose that in mice aorta neuronal (n)NOS-derived H2O2 accounts for a large proportion of endothelium-dependent ACh-induced relaxation. In mice aorta rings, ACh-induced relaxation was inhibited by L-NAME and Nomega-nitro-L-arginine (L-NNA), two nonselective inhibitors of NOS, and attenuated by selective inhibition of nNOS with L-ArgNO2-L-Dbu-NH2 2TFA (L-ArgNO2-L-Dbu) and 1-(2-trifluoromethylphehyl)imidazole (TRIM). The relaxation induced by ACh was associated with enhanced H2O2 production in endothelial cells that was prevented by the addition of L-NAME, L-NNA, L-ArgNO2-L-Dbu, TRIM, and removal of the endothelium. The addition of catalase, an enzyme that degrades H2O2, reduced ACh-dependent relaxation and abolished ACh-induced H2O2 production. RT-PCR experiments showed the presence of mRNA for eNOS and nNOS but not inducible NOS in mice aorta. The constitutive expression of nNOS was confirmed by Western blot analysis in endothelium-containing vessels but not in endothelium-denuded vessels. Immunohistochemistry data confirmed the localization of nNOS in the vascular endothelium. Antisense knockdown of nNOS decreased both ACh-dependent relaxation and ACh-induced H2O2 production. Antisense knockdown of eNOS decreased ACh-induced relaxation but not H2O2 production. Residual relaxation in eNOS knockdown mouse aorta was further inhibited by the selective inhibition of nNOS with L-ArgNO2-L-Dbu. In conclusion, these results show that nNOS is constitutively expressed in the endothelium of mouse aorta and that nNOS-derived H2O2 is a major endothelium-dependent relaxing factor. Hence, in the mouse aorta, the effects of nonselective NOS inhibitors cannot be solely ascribed to NO release and action without considering the coparticipation of H2O2 in mediating vasodilatation.

[From normative power to human development--the search for upkeep of health]. / Do poder normativo à concepção de desenvolvimento humano--a busca da sustentabilidade em saúde.

This paper pretends to introduce a reflection about the notion of sustainable development in planning and generating practices and technologies concerned to health and, particularly, nursing. It questions the current model of development and its implications in health concepts and practices in a perspective of living quality.

[Power, interdependence and complementarity in hospital work: an analysis from the nursing point of view]. / Poder, interdependência e complementaridade no trabalho hospitalar: uma análise a partir da enfermagem.

This essay intends to discuss recent transformation both to hospital work and nursing work specifically. Analysis privilege inter and intra relations with multidisciplinary teams which is constituted of practices on the therapeutic process present in hospital space-time.

The role of the distal nephron in the regulation of acid-base equilibrium by the kidney.

The present paper reviews mechanisms by which the kidney controls systemic acid-base balance, with emphasis on the role of the distal nephron, and particularly of the cortical distal tubule. These mechanisms are essentially based on H-ion transport along the whole nephron. In proximal tubule cells, approximately 80% of H-ion secretion is mediated by Na+/H+ exchange, and 20% by H(+)-ATPase. In the distal nephron, acid-base transport mechanisms are located mainly in intercalated cells. H-ion secretion is effected by vacuolar H(+)-ATPase in alpha-intercalated cells and, in K-depleted animals, also by the gastric type H/K ATPase. In animals in alkalosis, beta-intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger, while a basolateral H-ATPase transfers H-ions into the interstitium. In cortical distal tubule, these mechanisms have been shown to be present in the intercalated cells of the connecting segment and of the initial collecting duct (the late distal tubule of micropuncture experiments). In the convoluted distal tubule (early distal tubule), most H-ion secretion occurs by means of the Na+/H+ exchanger. These data show that the distal nephron, including the cortical distal tubule, is a nephron segment responsible for a sizeable portion of bicarbonate reabsorption and titratable acid generation, as well as for bicarbonate secretion under appropriate metabolic conditions, being therefore the site of fine regulation of renal mechanisms that maintain acid-base homeostasis.

The role of the distal nephron in the regulation of acid-base equilibrium by the kidney

The present paper reviews mechanisms by which the kidney controls systemic acid-base balance, with emphasis on the role of the distal nephron, and particularly of the cortical distal tubule. These mechanisms are essentially based on H-ion transport along the whole nephron. In proximal tubule cells, approximately 80 of H-ion secretion is mediated by Na+/H+ exchange, and 20 by H(+)-ATPase. In the distal nephron, acid-base transport mechanisms are located mainly in intercalated cells. H-ion secretion is effected by vacuolar H(+)-ATPase in alpha-intercalated cells and, in K-depleted animals, also by the gastric type H/K ATPase. In animals in alkalosis, beta-intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger, while a basolateral H-ATPase transfers H-ions into the interstitium. In cortical distal tubule, these mechanisms have been shown to be present in the intercalated cells of the connecting segment and of the initial collecting duct (the late distal tubule of micropuncture experiments). In the convoluted distal tubule (early distal tubule), most H-ion secretion occurs by means of the Na+/H+ exchanger. These data show that the distal nephron, including the cortical distal tubule, is a nephron segment responsible for a sizeable portion of bicarbonate reabsorption and titratable acid generation, as well as for bicarbonate secretion under appropriate metabolic conditions, being therefore the site of fine regulation of renal mechanisms that maintain acid-base homeostasis.

Mechanism of acidification along cortical distal tubule of the rat.

The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.

Transepithelial pH gradients in cortical distal tubules during metabolic alkalosis.

1. The cortical distal tubule of the rat kidney participates in the regulation of acid-base balance, showing bicarbonate reabsorption, secretion or absence of transport under different experimental conditions. In the present study, we measured differences in transepithelial pH using double ion-exchange resin/reference microelectrodes in control and alkalotic (chronic plus acute) male Wistar rats and in alkalotic rats receiving a K+ supplement in diet and infusion. 2. pH was measured in the tubule lumen during stationary microperfusion with 25 mM bicarbonate Ringer solution, and in peritubular vessels next to the perfused tubules. 3. Differences in transepithelial pH were 0.70 +/- 0.12 (N = 16) pH units in early distal tubules (ED) and 1.03 +/- 0.050 (N = 15) in late distal tubules LD) of control rats, 0.22 +/- 0.056 (N = 17) in ED and 0.25 +/- 0.050 (N = 20) in LD of alkalotic rats, and -0.02 +/- 0.039 (N = 24) in ED and -0.02 +/- 0.040 (N = 24) in LD of K(+)-supplemented alkalotic rats. 4. In control rats, the transepithelial potential difference (PD) (-8.9 +/- 1.45 mV (N = 16) in ED and -32.7 +/- 2.99 mV (N = 15) in LD) was not large enough to explain transepithelial H+ and HCO3- gradients, suggesting the presence of an active transport mechanism responsible for their maintenance. 5. The present data show that the cortical distal tubule is able to establish transepithelial pH (HCO3-) differences, that these differences are reduced by alkalosis and abolished by alkalosis plus K+ supplementation, and that, although inversion of pH gradients (evidence for bicarbonate secretion) was observed in individual tubules, this inversion was not significant in the groups studied.

Transepithelial pH gradients in cortical distal tubules during metabolic alkalosis

1. The cortical distal tubule of the rat kidney participates in the regulation of acid-base balance, showing bicarbonate reabsorption, secretion or absence of transport under different experimental conditions. In the present study, we measured differences in transepithelial pH using double ion-exchange resin/reference microelectrodes in control and alkalotic (chronic plus acute) male Wistar rats and in alkalotic rats receiving a K+ supplement in diet and infusion. 2. pH was measured in the tubule lumen during stationary microperfusion with 25 mM bicarbonate Ringer solution, and in peritubular vessels next to the perfused tubules. 3. Differences in transepithelial pH were 0.70 +/- 0.12 (N = 16) pH units in early distal tubules (ED) and 1.03 +/- 0.050 (N = 15) in late distal tubules LD) of control rats, 0.22 +/- 0.056 (N = 17) in ED and 0.25 +/- 0.050 (N = 20) in LD of alkalotic rats, and -0.02 +/- 0.039 (N = 24) in ED and -0.02 +/- 0.040 (N = 24) in LD of K(+)-supplemented alkalotic rats. 4. In control rats, the transepithelial potential difference (PD) (-8.9 +/- 1.45 mV (N = 16) in ED and -32.7 +/- 2.99 mV (N = 15) in LD) was not large enough to explain transepithelial H+ and HCO3- gradients, suggesting the presence of an active transport mechanism responsible for their maintenance. 5. The present data show that the cortical distal tubule is able to establish transepithelial pH (HCO3-) differences, that these differences are reduced by alkalosis and abolished by alkalosis plus K+ supplementation, and that, although inversion of pH gradients (evidence for bicarbonate secretion) was observed in individual tubules, this inversion was not significant in the groups studied

[The thinking about women, health and work in the hospital]. / Pensando mulher, saúde e trabalho no hospital.

This article deals with the relation women, health and work at hospital. Working relationships are thought in a gender perspective represented in a sexual division of work. Through a discussion about this subject, we intend to rise questions and reflect upon the reality of health care female workers.

PCO2 in renal cortex.

In a number of recent investigations a renal cortical PCO2 higher than that of systemic blood was reported. We have studied this problem with the use of micro-Severinghaus electrodes based on antimony, H+ liquid ion exchange, and glass pH electrodes with an inner buffer solution containing 0.5 mg/ml carbonic anhydrase (CA). Measurements in renal cortical structures (renal tubules, star vessels, capillaries, and glomeruli in Munich-Wistar rats) were compared with determinations in renal vein or artery performed with the same electrode in sequence. No significant differences in PCO2 were found between cortical structures and renal vein in control rats, in metabolic alkalosis, respiratory acidosis and alkalosis, and after CA inhibition. Nevertheless, absolute PCO2 levels, which followed the PCO2 of systemic blood, were markedly different in these groups. Measurements of pH and PCO2 at the same tubule site were compatible with HCO3- determinations in tubule fluid in vitro (made with use of the Henderson-Hasselbalch equation) in control rats. When proximal tubules were pump-perfused in vivo with a solution containing 30 mM NaHCO3, measured PCO2 approached that of the perfusing solution at high pump rates, and approached the free-flow value as rates were reduced to zero, indicating that the CO2 generated in the lumen equilibrated rapidly across the epithelium. Reducing renal blood flow by aortic clamping reduced renal cortical PCO2. In conclusion, in a large number of experimental conditions renal cortical PCO2 was never higher than that measured in systemic blood.

Sodium dependence of early distal H+ secretion in rat kidney.

In order to study the mechanism of H-ion secretion in cortical distal tubules of the rat kidney, the luminal pH and transepithelial potential difference (PD) were measured with double-barrelled, pH-sensitive, resin/reference microelectrodes. Perfusion of peritubular capillaries with low-sodium solutions increased luminal pH by 0.28 +/- 0.024 units. Perfusion of the lumen with 1 mM amiloride increased luminal pH by 0.67 +/- 0.01 units. These changes could not be attributed to modification of transepithelial PD. We conclude that early distal acidification is sodium-dependent, possibly owing to the presence of Na+/H+ exchange.

Sodium dependence of eraly distal H+ secretion in rat kidney

In order to study the mechanism of H-ion secretion in cortical distal tubules of the rat kedney, the luminal pH and transepithelial potential difference (PD) were measured with double-barrelled, pH-sensitive, resin/reference microelectrodes. perfusion of peritubular capillaries with low-sodium solutions increased luminal pH by 0.28 ñ 0.024 units. Perfusion of the lumen with 1 m§ amiloride increased luminal pH by 0.67 ñ 0.01 units. These changes could not be atributed to modification of transepithelial PD. We conclude that early distal acidification is sodium-dependent, possibly owing to the presence of Na+/H+ exchange