Recently, we have established a model of severe stepwise normovolemic hemodilution to a hematocrit of 10 % in rats employing three different colloidal volume replacement solutions (Voluven, Volulyte and Gelafundin) that are routinely used in clinical practice at present. We did not see severe dilutional acidosis as to be expected, but a decline in urinary pH. We here looked on further mechanisms of renal acid excretion during normovolemic hemodilution. Bicarbonate, which had been removed during normovolemic hemodilution, was calculated with the help of the Henderson-Hasselbalch equation. The urinary amount of ammonium as well as phosphate was determined in residual probes. The absolute amount of free protons in urine was obtained from the pH of the respective samples. The amount of protons generated during normovolemic hemodilution was approximately 0.6 mmol. During experimental time (5.5 h), distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39 mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer constituted 0.04 mmol in every experimental group. Excretion of free protons was in the range of 10-6 mmol. The present data prove that the prompt rise in urinary ammonium excretion is also valid for acute metabolic acidosis originating from severe normovolemic hemodilution., J. K. Teloh, I. N. Waack, H. de Groot., and Obsahuje bibliografii
Studies have demonstrated that heat shock protein 70 (HSP70) plays an important role in the protection of stressed organisms. The development of strategies for enhancing HSPs expression may provide novel means of minimizing inflammatory lung conditions, such as acute lung injury. This study aimed to examine the effect of L-alanyl-L-glutamine (GLN) inhalation in enhancing pulmonary HSP72 (inducible HSP70) expression and attenuating lung damage in a model of acute lung injury induced by Lipopolysaccharide (LPS) inhalation. The experimental rats were randomly assigned to one of four experimental groups: (1) NS: saline inhalation; (2) NS-LPS: pretreatment by saline inhalation 12 h before LPS inhalation; (3) GLN: glutamine inhalation; (4) GLN-LPS: pretreatment by glutamine inhalation 12 h before LPS inhalation. The results show that GLN compared with saline administration, led to significant increase in lung HSP72 both in non LPS-treated rats and LPS-treated rats. In LPStreated rats, pretreatment by GLN inhalation produced less lung injury as evidenced by the decrease in lung injury score and dramatic decrease in lactate dehydrogenase (LDH) activity and polymorphonuclear leukocyte cell differentiation counts (PMN %) in the bronchoalveolar lavage fluid. The study indicates that prophylactic glutamine inhalation associated with the enhancement of HSP72 synthesis attenuates tissue damage in experimental lung injury., I.-C. Chuang, M.-S. Huang, L.-J. Huang, S.-H. Chou, T.-N. Tsai, Y.-C. Chen, R.-C. Yang., and Obsahuje bibliografii
Recently, we have established that slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of euthyroid (EU) Lewis rats posses the same proportions between their four myosin heavy chain (MyHC) mRNAs , protein isoforms and fiber types as determined by real time RT-PCR, SDS-PAGE and 2-D stereological fiber type analysis, respectively. In the present paper we investigated if these proportions are maintained in adult Lewis rats with hyperthyroid (HT) and hypothyroid (HY) status. Although HT and HY states change MyHC isoform expression, results from all three methods showed that proportion between MyHC mRNA-1, -2a, -2x/d, -2b , protein isoforms MyHC-1, -2a, -2x/d, -2b and to lesser extent also fiber types 1, 2A, 2X/D, 2B were preserved in both SOL and EDL muscles. Furthermore, in the SOL muscle mRNA expression of slow MyHC-1 remained up to three orders higher compared to fast MyHC transcripts, which explains the predominance of MyHC-1 isoform and fiber type 1 even in HT rats. Although HT status led in the SOL to increased expression of MyHC-2a mRNA, MyHC-2a isoform and 2A fibers, it preserved extremely low expression of MyHC-2x and -2b mRNA and protein isoforms, which explains the absence of pure 2X/D and 2B fibers. HY status, on the other hand, almost completely abolished expression of all three fast MyHC mRNAs , MyHC protein isoforms and fast fiber types in the SOL muscle. Our data present evidence that a correlation between mRNA , protein content and fiber type composition found in EU status is also preserved in HT and HY rats., T. Soukup, M. Diallo., and Obsahuje bibliografii
Proteasomes appear to be involved in the pathophysiology of various acute and chronic lung diseases. Information on the human lung proteasome in health and disease, however, is sparse. Therefore, we studied whether end-stage pulmonary diseases are associated with alterations in lung 20S/26S proteasome content, activity and 20S subunit composition. Biopsies were obtained from donor lungs (n=7) and explanted lungs from patients undergoing lung transplantation because of end stage chronic obstructive pulmonary disease (COPD; n=7), idiopathic pulmonary fibrosis (IPF, n=7) and pulmonary sarcoidosis (n=5). 20S/26S proteasomes in lung extracts were quantified by ELISA, chymotrypsin-like proteasome peptidase activities measured and 20S proteasome β subunits analyzed by Western blot. As compared with donor lungs, proteasome content was increased in IPF and sarcoidosis, but not in COPD. The relative distribution of free 20S and 26S proteasomes was similar; 20S proteasome was predominant in all extracts. Proteasome peptidase activities in donor and diseased lungs were indistinguishable. All extracts contained a mixed composition of inducible 20S β immuno-subunits and their constitutive counterparts; a disease associated distribution could not be identified. A higher content of lung proteasomes in IPF and pulmonary sarcoidosis may contribute to the pathophysiology of human fibrotic lung diseases., T. A. Baker, H. H. Bach IV, R. L. Gemelli, R. B. Love, M. Majetschak., and Obsahuje bibliografii