Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn.

Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement. In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-α, IL-6, IL-8, and IL-10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily. NAC treatment increased GSH level on days 4-5 (p<0.05) and PSH level on days 2-6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4-5 (p<0.05), IL-8 on days 4-6 (p<0.05) and IL-10 on days 4-6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score. NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement.

Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury.

Oxidative stress and inflammatory processes generate edema in burns. Treatment of consequent hypovolemia is a challenge. The aim of study was to assess if glutathione pro-drug N-acetylcysteine (NAC) can influence inflammation and fluid requirement. We also aimed to compare organ functions scores and vasoactive drug requirement. This prospective randomised study involved 28 patients with burn injury affecting more than 20% of body surface area. Fourteen patients were on standard therapy, whereas for other 14 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Leukocyte surface marker expressions were determined, multiple organ function scores, use of vasopressor agents and fluid requirements were recorded daily. Expression of CD11a (p < 0.05), CD18 (p < 0.05) and CD97 (p < 0.01) on the granulocytes were significantly lower in the NAC treated group, similarly to lymphocyte CD 49d (p < 0.05) and monocyte CD 49d (p < 0.01) and CD 97 (p < 0.05) expression. No significant difference was found in the fluid requirement between groups but patients the NAC group required less vasopressor and inotropic drugs from day 4. NAC treatment is associated with a less pronounced inflammation reflected in lower CD marker expression and vasopressor requirement.

Combined retrograde tracing and immunocytochemical identification of luteinizing hormone-releasing hormone- and somatostatin-containing neurons projecting to the median eminence of the rat.

LHRH and somatostatin or somatotropin-release inhibiting factor (SRIF) are produced by neurons whose cell bodies are located in telencephalic and diencephalic regions in the rat. Many, but not all, of these neurons project to the external zone of the median eminence (ME), where the peptides are released from the nerve terminals into hypophysial portal vessels. In the present study, we identified these neurons by in vivo injection of a retrograde tracer, the lectin wheat germ agglutinin (WGA), into the external zone of the ME. Subsequently, colchicine was given into the lateral ventricle 10-24 h after the WGA injection. The animals were killed 24-48 h after the WGA injection. Vibratome sections of the brains were stained for both WGA and LHRH or SRIF with a dual immunocytochemical technique. Approximately 70% of the LHRH neurons in the septum and the anterior hypothalamus and about 70% of the SRIF neurons in the medial preoptic area, the anterior periventricular area, and the paraventricular nucleus were double labeled, indicating that they projected to the ME. None of the SRIF neurons in the ventromedial and arcuate nuclei were labeled with WGA. Double labeled LHRH cells were either smooth and fusiform or spiny. WGA-accumulating LHRH or SRIF perikarya were intermixed with single labeled LHRH or SRIF cells, which apparently did not project to the ME. The results indicate that there are at least two populations of LHRH neurons in the preoptic-septal region and two populations of SRIF neurons in the medial preoptic and anterior periventricular areas and the paraventricular nucleus of the rat brain: one with access to the portal capillaries of the ME and, therefore, functionally related to the regulation of the pituitary, and another without access to portal capillaries, perhaps functionally related to intracerebral neurotransmission or modulation. Moreover, some hypophysiotropic LHRH and SRIF neurons may have axon collaterals reaching multiple targets within the central nervous system.

The hypothalamo-infundibular growth hormone-releasing hormone (GH-RH) system of the rat.

Two to 10 days after complete unilateral surgical isolation of the medial basal hypothalamus (MBH) or 3 months following neonatal monosodium glutamate (MSG) treatment, the presence of growth hormone-releasing hormone (GH-RH) immunoreactive neuronal structures was studied in rats using vibratome sections and GH-RH immunocytochemistry. Neonatal MSG treatment resulted in a dramatic decrease of GH-RH immunoreactivity in the median eminence (ME), but not complete disappearance as reported earlier. Unilateral complete deafferentation of the MBH caused only a slight decrease in GH-RH immunostaining in the posterior regions of the ipsilateral median eminence (ME). At this level GH-RH accumulation was observed in scattered transected fibers lateral to the cut, outside of the MBH. Our findings indicate that the arcuate nucleus is the major source of GH-RH immunoreactive structures in the ME. Although, however, in very small numbers, the existence of other sources of GH-RH terminals cannot be excluded.