The granin (chromogranin/secretogranin) family

The chromogranins/secretogranins, referred to in abbreviated form as granins, are a family of acidic secretory proteins that are found in the secretory granules of a wide variety of endocrine cells and neurons, being stored together with many different peptide hormones and neuropeptides. The recent elucidation of their primary structure has provided insights into possible functions of these proteins. Moreover, the granins have been successfully used as markers for normal and neoplastic endocrine and neuronal cells, as well as model proteins to understand the sorting mechanism involved in the formation of secretory granules.     

Localized increases in ovarian vascular permeability and leucocyte accumulation after induced ovulation in rabbits.

Colloidal carbon was injected i.v. in mature virgin rabbits at different times after induction of ovulation by human chorionic gonadotrophin (hCG, 100 iu) or mating. Before induction of ovulation, slight carbon leakage was observed in the inner vascular ring of the theca interna of antral follicles, but blood vessels in the other ovarian compartments were unstained. Between 4 and 10.5 h after hCG-treatment or mating, vascular leakage was most marked in the blood vessels of the interstitial gland and in the theca interna of antral follicles. Just before ovulation, carbon particles were observed between granulosa cells and some carbon was seeping into the follicular fluid of preruptured follicles. Vascular leakage was also observed over the follicle dome before rupture as well as at the dorsomedial junction between the mesovarium and the ovary. The blood vessels stained with carbon were 7-70 microns diameter, representing capillaries and postcapillary venules. About 6 h after hCG injection, an increased number of polymorphonuclear leucocytes migrated from the vessels of these ovarian compartments into the surrounding interstitial tissue. The number of leucocytes seen in the follicular wall and ovarian medulla increased markedly towards ovulation. During early corpus luteum formation, the number of leucocytes decreased markedly. The localized vascular changes seen after mating and hCG stimulation were similar to an inflammatory reaction and could form the basis for the formation of peritoneal exudate after ovulation in rabbits and periovulatory ascitic accumulation seen in the peritoneal cavity of women during the menstrual cycle.     

Interaction of phenolsulphonphthalein dyes with rabbit plasma and rabbit serum albumin.

Interaction of various substituted phenolsulphonphthalein dyes to rabbit plasma and rabbit serum albumin has been studied by ultrafiltration, equilibrium dialysis and spectrophotometry. The results obtained by ultrafiltration and equilibrium dialysis showed that the degree of binding of these dyes to protein increases in the following order: Phenol red less than bromophenol blue less than bromocresol green less than bromothymol blue. Analysis of binding results revealed that five molecules of bromothymol blue bound very strongly to a molecule of rabbit albumin, whereas only two and three molecules of bromophenol blue and bromocresol green strongly interact with the protein, respectively. It is suggested that strong binding of these substances to protein may be related to the hydrophobicity of these compounds. Finally, an attempt has been made to evaluate the possibility, whether the spectral changes occurred during interaction of dyes to albumin can be utilized for the determination of binding of these ligands to proteins.     

Effect of antihistamines and chlorpromazine on the calcium-induced hyperpolarization of the Amphiuma red cell membrane

1. 1. It has previously been demonstrated that an increase in extracellular Ca²⁺ concentration induces a transient increase in K⁺ permeability and associated hyperpolarization of the red cell membrane of the giant salamander, Amphiuma means. This phenomenon is analogous to the Ca²⁺-induced KCl loss observed in ATP-depleted human red cells and red cell ghosts.

2. 2. Histamine, which enhances the Ca²⁺-induced K⁺ loss from depleted human red cells, is without effect on this Ca²⁺-induced hyperpolarization of Amphiuma red cells.

3. 3. Promethazine (10 μM) and mepyramine (1 mM), which inhibit the Ca²⁺-induced K⁺ loss in depleted human red cells, also block the Ca²⁺-related hyperpolarization of Amphiuma erythrocytes.

4. 4. Chlorpromazine (25 μM), despite being a weak antihistamine, is equally effective in blocking the Ca²⁺-induced hyperpolarization of Amphiuma red cells.

5. 5. Ionophore A23187 causes a large and sustained Ca²⁺/K⁺-dependent hyperpolarization even in the presence of normal (1.8 mM) concentrations of Ca²⁺. This hyperpolarization is relatively insensitive to chlorpromazine and promethazine.

6. 6. The inhibition of the Ca²⁺-induced hyperpolarization of the Amphiuma red cell membrane by chlorpromazine and promethazine may be related to their properties as local anaesthetics.

Glycine hydrazide as a bifunctional reagent for the synthesis of antigens with steroids as the immunodeterminant groups (author's transl)]

The suitability of glycine hydrazide as a link between steroids and carrier proteins in the synthesis of antigens was examined. Testosterone was used as hapten; bovine serum albumin as carrier protein. The reaction described here of testosterone with glycine hydrazide to form testosterone glycylhydrazone acetate took place under milk conditions and the yield was nearly quantitative. Rabbits immunized with the new antigen developed specific antibodies against testosterone.     

Complete and Defective Bacteriophages of Classical Vibrio cholerae: Relationship to the Kappa Type Bacteriophage

The Classical Vibrio cholerae strain NIH 41 contains two temperate bacteriophages, designated VcA-1 and VcA-2, that are distinguished by immunity, plaque morphology, induction kinetics, and particle morphology. Both phage are serologically related to phage Kappa. However, only phage VcA-2 has the Kappa type host range and immunity. The induction kinetics and immunity patterns of Classical vibrios suggest that these strains may contain defective phage related to the phages isolated from NIH 41. Classical strain 569B releases phage-tail structures upon induction that are morphologically and serologically related to both phages VcA-1 and VcA-2. The possible reason for the defectiveness of these phages in 569B is discussed. It is concluded that complete or defective bacteriophages of the Kappa type morphology and serology are extremely prevalent in V. cholerae, regardless of biotype.     

Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

Background

A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.

Methods and Results

Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.

Conclusions

Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.