Synthesis and acid ionization constants of cyclic cystine peptides

Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-_n-Cys(Trt)-OBu^t] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK¹= 2.35–2.84) and to terminal amino group (pK₂= 5.61–6.93); pK₁, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK₂, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH⁺₃-) formation.     

Potentiation and restitution of heart muscle contraction in rats adapted to exercise

The original amplitude of contraction of strips of myocardium determined the inotropic response to paired stimulation. The higher the initial amplitude, the lower the degree of potentiation and the higher the degree of restitution of contraction. For equal amplitude, the degree of potentiation of myocardial contraction of exercise-adapted rats was greater and the degree of restitution smaller than in the control. These changes probably reflect changes in the ion transport system of the myocardial cells.Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 780–782, July, 1976.     

Relationship between frequency and amplitude of myocardial contractions in rats adapted to heat

After preliminary adaptation of rats to heat (for 3 h daily at 35°C for 1 month) the amplitude of contractions of the isolated papillary muscles from the left ventricle at 28°C at high frequency was higher than in control animals. This difference persisted at 36°C and disappeared at 25°C. It is postulated that adaptation to heat leaves a definite structural imprint in heart muscle cells.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Institute of Physiology and Experimental Pathology of the Arid Zone, Academy of Sciences of the Turkmenian USSR, Ashkhabad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1168–1170, October, 1976.     

Counseling Fathers (2010) by C.Z. Oren and D.C. Oren

No abstract available for this article.     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.