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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5 || Follicle and follicular cells research abs 1 || Interferon research abs 1 || Hemoglobin research abs

Eur J Appl Physiol Occup Physiol. 1975 Dec 5;34(4):227-32.
Changes in erythrocyte 2,3 diphosphoglycerate in women following short term maximal exercise.

Bonner HW, Tate CA, Buffington CK.

15 untrained women were subjected to a walking treadmill test to determine the influence of maximal exercise upon synthesis of erythrocyte 2,3 DPG. Although there was a 9.8% increase in the 2,3 DPG content following exercise, there was a concomitant 9.4% increase in the hemoglobin level; therefore, when 2,3 DPG is expressed as a ratio to hemoglobin (See Article), there was no significant change as a result of exercise stress. It was suggested that three additive factors produced during strenuous exercise; decreased pH; increased hemoglobin concentration; and increased CO2 production result in by-product inhibition of 2,3 DPG synthesis. It is concluded that 2,3 DPG does not provide a physiologic benefit in the adaptation of the oxygen transport system to exercise.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=234&dopt=Abstract

Eur J Biochem. 1975 Jul 1;55(2):385-90.
Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests.

Chiancone E, Norne JE, Forsen S, Bonaventura J, Brunori M, Antonini E, Wyman J.

35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=236&dopt=Abstract

J Biol Chem. 1975 Dec 25;250(24):9250-5.
Hemoglobin Deer Lodge (beta 2 His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site.

Bonaventura J, Bonaventura C, Sullivan B, Godette G.

Hemoglobin Deer Lodge is an abnormal human hemoglobin with arginine substituted for histidine at the beta 2 position. X-ray crystallography of normal human hemoglobin has shown that the beta 2 residue is normally part of the binding site for 2,3-diphosphoglycerate. The substitution of arginine for histidine at beta 2 affects both the kinetics and equilibria of ligand binding. When stripped of anions, Hb Deer Lodge has an increased oxygen affinity and a decreased degree of cooperativity relative to Hb A. The alkaline Bohr effect is slightly increased and there are marked increases in oxygen affinity below pH 6 and above pH 8. In the presence of 2,3-diphosphoglycerate the cooperativity in increases to nromal and the pH dependence of oxygen binding is reduced. This contrasts with the enhanced Bohr effect seen for Hb A in the presence of organic phosphates. Due to enhanced anion binding at high pH, Hb Deer Lodge has a slightly lower oxygen affinity than Hb A at pH 9 in the presence of 2,3-diphosphoglycerate or inositol hexaphosphate. Kinetic studies at neutral pH in the absence of organic phosphates revealed biphasicity in the rate of oxygen dissociation from Hb Deer Lodge, while approximately linear time courses were observed for Hb A. The fast phase of the oxygen dissociation kinetics shows great pH sensitivity, and organic phosphates increase the rate and percentage of the fast phase without greatly affecting the slow phase. The two phases are not resolvable at high pH. CO combination kinetics are much like those of Hb A except that "fast" and "slow" phases were apparent at wavelengths near the deoxy-CO isobestic point. We suggest that functional differences between the alpha and beta chains are enhanced in Hb Deer Lodge. After flash photolysis of the CO derivative, the percentage of quickly reacting material was slightly greater for Hb Deer Lodge than for Hb A. This may imply a somewhat greater tendency to dissociate into high affinity subunits. The substitution of arginine for histidine at beta 2 thus results in a macromolecule whose ligand-binding properties are significantly altered, the primary differences being expressed at high pH where Hb Deer Lodge binds anions more strongly than Hb A. The properties of Hb Deer Lodge are compared to those of other hemoglobin variants with substitutions at residues involved in binding of 2,3-diphosphoglycerate.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=393&dopt=Abstract

J Perinat Med. 1975;3(1):53-67.
Recognition and significance of maternogenic fetal acidosis during intensive monitoring of labor.

Roversi GD, Canussio V, Spennacchio M.

FHR monitoring and microanalysis of fetal blood are mutually complementary procedures, and optimal knowledge of the fetal state is achieved by making use of both, the former for the preliminary screening of all cases at risk and the latter for the purpose of deciding on obstetric management where pathological changes are evident in the FHR. The major difficulty in obtaining a precise value for the fetal acid-base balance lies in the occurence of "falsely abnormal" cases, i.e. cases in which the fetal pH falls during labor but the clinical condition at birth is good (APGAR greater than or equal to 7). In our own series the incidence of such cases among fetuses at risk was 11.2% (Tab. I). In the majority of these cases the fetal acidosis is thought to be a result of increased metabolic acidosis in the mother (maternogenic fetal metabolic acidosis). The importance of the maternogenic fetal acidosis during labor lies in the fact that unless it is recognised, rapid extraction of the fetus will appear necessary on clinical grounds, although it is in fact unnecessary, since this form of acidosis has no adverse effect on the fetus. Various parameters have been proposed for the differential diagnosis of the maternogenic fetal acidosis. These include the feto-maternal difference in base deficit (F/M deltaBD), the materno-fetal differences in pHqu 40 (M/F deltapHqu 40) the materno-fetal difference actual pH (M/F actual deltapH), and the materno-fetal difference in base deficit of the extra-cellular fluid (M/F deltaBDHb5). A critical analysis of these parameters has been carried out on the results of microtests performed during a 5 year period (1968-1972) at the First Clinic of Obstetrics and Gynecology of Milan University. The cases comprised 59 regarded as normal (normal course of pregnancy, spontaneous commencement of labor at term, clear amniotic fluid, regular FHR, spontaneous birth, APGAR at 90 sec between 8 and 10, weight at birth greater than 2500 g), and 335 considered to be at risk (maternal disease, presence of meconium stained amniotic fluid and/or abnormal changes in FHR). In all of these cases the FHR was recorded by cardiotokography, and the tracings were interpreted according to HON. Microsamples of blood were taken from both mother and fetus during labor and the following determinations were carried out: actual pH, pHqu 40, Hb concentration, hemoglobin oxygen saturation, base deficit Hb5 (BDHb5). The maternofetal differences were then calculated. The same determinations were carried out on samples of maternal blood and of arterial and venous cord blood taken immediately after delivery. The clinical condition of the infant was evaluated by the APGAR score at 90 seconds after birth.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=480&dopt=Abstract

Am J Manag Care. 2003 Mar;9(3):213-7.
Slow response to loss of glycemic control in type 2 diabetes mellitus.

Brown JB, Nichols GA.

Kaiser Permanente Center for Health Research, Portland, Ore 97227-1110, USA. jonathan.browpchr.org

BACKGROUND: To achieve glycemic control in type 2 diabetes mellitus, the American Diabetes Association (ADA) recommends intensification of glucose-lowering therapy when the glycosylated hemoglobin (HbA1c) level exceeds 8.0%. OBJECTIVE: To study glycemic control before and after initiation of secondary antihyperglycemic therapy to better understand the pace and patterns of therapeutic failure and clinical responses to failure. STUDY DESIGN: A retrospective, population-based observational study. PATIENTS AND METHODS: From a 12-year-old diabetes registry of members of Kaiser Permanente Northwest, a large group-model HMO, we tracked the glycemic control histories of all 570 registrants who, in 1998, added metformin therapy to sulphonylurea monotherapy. RESULTS: The last HbA1c level before metformin use averaged 9.4%. Metabolic decompensation accelerated over time. Patients typically spent numerous months at and had several measurements of HbA1c >8.0% before a final glycemic spike to >9.0%. Persons experiencing more gradual failure accumulated greater glycemic burdens before changing therapy. CONCLUSIONS: The level of HbA1c that seemed to trigger glucose-lowering action was 9.0% or higher, not 8.0% as recommended by the ADA. A substantial hyperglycemic peak preceded change in therapy even in this relatively tightly controlled population with type 2 diabetes mellitus. Earlier therapeutic changes, but not more frequent testing, would prevent the glycemic excursions we observed. Low mean HbA1c levels in populations do not necessarily indicate that loss of glycemic control is being rapidly addressed for most patients. More research is needed to estimate the impact of these peaks on current well-being and future complications.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12643338&dopt=Abstract

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