Calcium metabolism in normal and thyro-parathyroidectomized goats

1. The effects of thyro-parathyroidectomy on calcium metabolism in the goat have been investigated using stable calcium balance techniques and the isotopes (45)Ca, (47)Ca and (85)Sr.2. Thyro-parathyroidectomized goats, whether receiving supplementary thyroxine or not, are in negative calcium balance, whereas normal or thyroidectomized animals are in positive balance.3. Gastro-intestinal absorption of (45)Ca is less in thyro-parathyroidectomized goats, whether receiving supplementary thyroxine or not, than in either normal goats or thyroidectomized goats receiving thyroxine supplements.4. The rate of endogenous secretion of calcium into the gastro-intestinal tract is unchanged by either thyroidectomy or thyro-parathyroidectomy. Urinary excretion of calcium is also apparently unchanged.5. The bone calcium accretion rate is reduced to approximately the same extent in thyroidectomized and thyro-parathyroidectomized goats. Thyroxine supplements restore the bone accretion rate of both groups of animals to normal or greater than normal levels.6. The bone calcium resorption rate is greater in thyro-parathyroidectomized goats, whether receiving thyroxine supplements or not, than in either normal goats or thyroidectomized goats receiving thyroxine supplements.     

The metabolism of C9 in normal subjects and in patients with autoimmune disease

The metabolism of the ninth component of complement (C9) was studied in eight healthy subjects and nine patients with autoimmune disease, including seven with systemic lupus erythematosus (SLE) and one each with mesangial IgA nephropathy and mixed essential cryoglobulinaemia. In normal subjects the metabolic parameters (mean ± s.d.) were: fractional catabolic rate (FCR): 2.92 ± 0.36%/h, plasma half-life (T_1/2): 42.5 ± 6.7 h, and extravascular/intravascular distribution ratio (EV/IV): 0.56 ± 0.12. In patients the FCR was 3.38 ± 0.70%/h, the T_1/2 was 37.6 ± 10.2 h, and the EV/IV was 0.55 ± 0.19. Patients with reduced total serum haemolytic activity (i.e. CH₅₀ < 68% of normal human serum (NHS), n = 7) had significantly higher FCR (3.57 ± 0.67%/h) and shorter T_1/2 (33.5 ± 6.8 h) than the control group (both P< 0.05). The plasma concentration of the terminal complement complex (i.e. soluble TCC or SC5b-9) was higher in patients (median (range): 515 (300–1879 μg/l)) than in normal subjects (313 (229–402 μg/l); P< 0.01) and showed a positive correlation with the FCR of C9 (r =0.61, P< 0.01). Plasma C9 production rate was also greater in patients (0.11 ± 0.05 mg/kg per h) compared with control subjects (0.07 ± 0.03 mg/kg per h, P< 0.05), and was associated with a higher C9 concentration in patients’ sera (76 ± 13 mg/lversus 61 ± 14 mg/l, P< 0.05). These results demonstrate that C9 is rapidly metabolized in normal humans and that hypercatabolism occurs in patients with autoimmune disease and complement activation. This was despite the presence of normal or elevated serum C9 levels and normal compartmental distribution.     

Serotonin modulation of cerebral glucose metabolism in normal aging

Age-related alterations in serotonin function may increase the vulnerability to psychiatric and neurodegenerative disorders in late life. The neuroendocrine and cerebral metabolic response to the acute administration of the selective serotonin reuptake inhibitor, citalopram (40mg, IV), was measured in 17 normal control subjects using positron emission tomography (PET) to evaluate changes in serotonin function with normal aging. The citalopram-induced change in cerebral metabolism was positively correlated with age in the right precuneus, right paracentral lobule, and left middle temporal gyrus and negatively correlated with age in the left anterior cingulate gyrus, right inferior and middle frontal gyri, right insula, and right inferior parietal lobule. The positive correlations in mainly posterior brain regions indicate that normal aging is associated with an increase in metabolism after citalopram administration, whereas the negative correlations in mainly anterior brain regions indicate that normal aging is associated with a greater decrease in metabolism. These results suggest different compensatory processes in anterior compared to posterior brain regions secondary to the age-related loss of serotonin innervation.     

Intravascular metabolism of normal and mutant mouse immunoglobulin molecules

The metabolism of IgG immunoglobulins in the body is tightly regulated in order to maintain their intravascular concentration. Different subclasses may have different intravascular half-lives, and in the mouse, passively administered IgG2b disappears from the circulation more rapidly than IgG2a. We have attempted to localize the sequences in the constant region which are responsible for this difference by examining the intravascular metabolism of mutant immunoglobulins that were generated in tissue culture and have undergone deletions of individual constant region domains or contain different combinations of gamma 2b and gamma 2a CH2 and CH3 domains. Our results suggest that the regulation of intravascular metabolism is complex but indicate that sequences in the CH3 domain are important in determining the different intravascular half-lives of IgG2b and IgG2a antibodies in the mouse.     

Energy metabolism of normal and lonidamine-treated Sertoli cells of rats

The effect of lonidamine on oxygen consumption, aerobic lactate production, and [U-14C]glucose metabolism of rat Sertoli cells was investigated. The results may be summarized as follows: (1) Sertoli cells show well-developed energy metabolism both in vitro and in vivo. (2) The rate of aerobic lactate production is markedly higher than in other cell types, either normal differentiated or neoplastic, such as Ehrlich ascites tumor cells. (3) Lonidamine does not affect respiration and aerobic glycolysis of Sertoli cells. This finding is consistent with previous data which demonstrated that the antispermatogenic effect can be mainly ascribed to an irreversible alteration of germ cell mitochondria induced by 1-substituted indazole-3-carboxylic acids of which lonidamine represents one of the most potent derivatives. (4) The functional impairment induced by lonidamine on rat Sertoli cells cannot be ascribed to an action on the energy metabolism even if, up to date, the biochemical target is still unclear.     

Myocardial substrate metabolism in the normal and failing heart

The alterations in myocardial energy substrate metabolism that occur in heart failure, and the causes and consequences of these abnormalities, are poorly understood. There is evidence to suggest that impaired substrate metabolism contributes to contractile dysfunction and to the progressive left ventricular remodeling that are characteristic of the heart failure state. The general concept that has recently emerged is that myocardial substrate selection is relatively normal during the early stages of heart failure; however, in the advanced stages there is a downregulation in fatty acid oxidation, increased glycolysis and glucose oxidation, reduced respiratory chain activity, and an impaired reserve for mitochondrial oxidative flux. This review discusses 1) the metabolic changes that occur in chronic heart failure, with emphasis on the mechanisms that regulate the changes in the expression of metabolic genes and the function of metabolic pathways; 2) the consequences of these metabolic changes on cardiac function; 3) the role of changes in myocardial substrate metabolism on ventricular remodeling and disease progression; and 4) the therapeutic potential of acute and long-term manipulation of cardiac substrate metabolism in heart failure.     

The effect of adrenalin on histamine metabolism in normal conditions and in diseases of the diencephalon

Summary This work deals with the changes induced by adrenalin injections in the histamine content, diamine oxidase activity and histaminopectic effect in healthy individuals and in patients with diencephalic afflictions adrenalin administration served as a functional test to assess the limits of homeostatic reactions in healthy and sick persons. In healthy individuals, the blood-histamine content decreases and the activity of diamine oxidase increases slightly, 10 minutes after subcutaneous injection of 0.3 ml of 0.1% adrenalin solution; as to the histaminopectic effect — no changes are seen. As distinct from the above, in patients with a diencephalic syndrome the blood-histamine content rises and the activity of diamine oxidase decreases somewhat. These changes, accompanied by a clinical reaction, are characteristic of some forms of diencephalic pathology and may be used for diagnosis.Corresponding Member AN SSSR N. I. Grashchenkov's Group in the Division of Biological Sciences of the AN SSSR, based on the Clinic for Nervous Diseases of the First Moscow Medical Institute (Director, Prof. G. N. Kassil) (Presented by Active Member AMN SSSR S. E. Severin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 50, No. 8, pp. 62–67, August, 1960