Hemopressin: a novel bioactive peptide derived from the alpha1-chain of hemoglobin

Hemopressin (PVNFKFLSH), a novel bioactive peptide derived from the alpha1-chain of hemoglobin, was originally isolated from rat brain homogenates. Hemopressin causes hypotension in anesthetized rats and is metabolized in vivo and in vitro by endopeptidase 24.15 (EP24.15), neurolysin (EP24.16), and angiotensin-converting enzyme (ACE). Hemopressin also exerts an antinociceptive action in experimental inflammatory hyperalgesia induced by carrageenin or bradykinin via a mechanism that is independent of opioids. These findings suggest that this peptide may have important regulatory physiological actions in vivo.

Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular preparations from rats

Nitric oxide (NO)-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg) at the presynaptic level increases the amplitude of muscular contraction (AMC) and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM) did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM) in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM) did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle

Variabilidade do controle glicêmico de pacientes com diabetes tipo 1 e tipo 2 durante um ano de acompanhamento / Variability of glicemic control of patients with type 1 and type2 diabetes during 1 retinue year

Para verificar a variabilidade do controle glicêmico em um estudo näo controlado de diabéticos durante um ano de acompanhamento, nós avaliamos retrospectivamente 113 paientes diabéticos. Com os valores das HBA1c (hemoglobina glicada) dosadas em 1998 calculamos um índice de controle que foi associado à idade, duraçäo do diabetes, IMC e dose de insulina. A HBA1c foi maior em pacientes DM1 doque DM2, respectivamente (7,9 (4,4-13,3) vs. 7,0 (4,4-13,4) por cento; p=0,007). Nos 90 pacientes com no mínimo duas HBA1c, 68 (75,6 por cento) mantiveram o controle: 51 (76,1 por cento)em bom, 8 (11,1 por cento) em regular e 9 (11,9 por cento) em péssimo controle. Nenhum manteve todas as HBA1c na faixa da normalidad, sendo que 26 pacientes (28,9 por cento) tiveram pelo menos um HBA1c normal. No grupo geral, 44 pacientes (48,9 por cento) apresentaram aumento da HBA1c, 41 (45,6 por cento) diminuiçäo e 5 pacientes (5,6 por cento) mantiveram o mesmo valor, sem diferença entre DM1 e DM2 (p=0,77). Observamos diferença na HBA1c e tempo de duraçäo de diabetes entre os pacientes com DM2 que tratavem com dieta, hipoglicemiante oral, terapia combinada e monoterapia com insulina, respectivamente (5,4 +/- 0,5 vs. 6,3 +/- 1,3 vs. 7,6 +/- 1,4 vs. 8,4 +/- 2,0 por cento; p= 0,001) e (8,5 +/- 9,9 vs. 5,3 +/- 4,2 vs. 14,1 +/- 9,6 vs. 16,9 +/- 8,1 anos; p= 0,003). O coeficiente de variaçäo intraindividual da HBA1c foi de 11,6 +/- 7,4 por cento (p= 0,0000), sendo de 12,8 +/- 7,6 por cento (p= o,0000) em DM1 e 10,4 +/- 7,2 por cento em DM2 (p= 0,0000) sem diferença entre ambos. Conclímos que em nossa amostra a maioria dos pacientes manteve um bom controle apesar da variabilidade intraindividual e da dificuldade em normalizar os níveis de HBA1c.

Vasoactive proterties of synthetic blood substitutes

There is a great need for the development of a safe and efficient blood substitute, to overcome the important limitations of homologous blood transfusion. Currently available cell-free hemoglobin-based oxygen-carrying solutions present oxygen transport and exchange properties similar to blood and potential benefits over conventional transfusion, including large supply, absence of transfusion reactions, no need for cross-matching, no risk for transmission of disease and long shelf life. Several experimental studies have suggested that cell-free hemoglobin is a vasoactive agent. In animal models of hemorrhagic shock, small doses of cell-free modified hemoglobin restore arterial pressure, promote adequate tissue oxygenation, and improve survival, when compared with fluids with no oxygen-carrying capacity. On the other hand, it has been demonstrated that hemoglobin-induced vasocontriction may result in decreased cardiac output, reduced blood flow to vital organs and severe pulmonary hypertension. Cell-free hemoglobin solutions cause their pressor effects by binding and scavenging nitric oxide. Although hemoglobin within the red blood cells is the natural scavenger of NO, when the hemoglobin is free in solution, NO is inactivated to a greater extend. Cell-free hemoglobins are on advanced clinical trials, despite the fact that development of a safe and efficient blood substitute depends on the availability of these products for critical evaluation by the scientific community before the widespread clinical use of these blood substitutes.

Effect of hemoglobin on the growth of mycobacteria and the production of siderophores.

Hemoglobin is known to support the growth of several bacterial species. The growth and the production of siderophores by 4 strains of mycobacteria in the presence of hemoglobin was studied in vitro. The findings were compared with those obtained in the presence of equivalent concentrations of iron in the medium. Increase in the concentrations of hemoglobin caused an appreciable increase in the growth of all 4 strains. This was however, accompanied by a significant decrease in the production of both exochelins and mycobactins. It was also observed that hemoglobin supported the growth of all strains as well as that with free iron and the concentrations of both siderophores was significantly higher in the presence of hemoglobin than in that of free iron.