ET Treatment Research Articles

Altered Ca2+ Homeostasis and Functional Correlates in Hepatocytes and Adipocytes in Endotoxemia and Sepsis

Decreased cytosolic [Ca2+] and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis. These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by [Ca2+]c and defective phosphorylation of relevant enzymes. Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae. ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic [Ca2+] under basal conditions and upon ACTH stimulation than that observed in cells of control rats. The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats. Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation.

Biological and biochemical activities of a toxoid of erythrogenic toxin type A

A toxoid of erythrogenic toxin type A (ET A) was prepared by formaldehyde treatment. Already 15 min after exposure to formaldehyde in isoelectric focusing the ET A band at pH 5.2 shifted to a band at pH 4.5. In Ouchterlony double diffusion test ET A and its toxoid were found to be identical, in fused rocket immuno-electrophoresis a reaction of partial identity was seen. Formaldehyde treatment of ET A resulted in an apparent increase of electrophoretic mobility. In contrast to ET A, its toxoid is non-mitogenic, non-pyrogenic and has lost its ability to induce delayed type hypersensitivity. Binding of ET A toxoid to human peripheral lymphocytes is of the same magnitude as binding of gold-labelled ET A.

IP3-dependent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats.

Inositol trisphosphate-dependent Ca2+ release was measured in saponin-permeabilized hepatocytes isolated from acutely (2 mg/100 g body wt iv) or chronically (0.1 mg X 100 g body wt-1 X 24 h-1 for 30 h) endotoxin-treated (ET, Escherichia coli) rats or from animals rendered septic by cecal ligation and puncture. A decrease of this parameter was observed in acutely ET-treated rats (52%, P less than 0.01) and after 30 h of continuous ET infusion (33%, P less than 0.01). Sepsis was associated with an elevated Ca2+ release (34%, P less than 0.01) as compared with the sham-operated animals. We conclude that during endotoxicosis and sepsis alterations of intracellular Ca homeostasis take place, reaching sites beyond the level of the plasma membrane. Such alterations could account in part for metabolic and functional changes associated with these pathologic states. In addition, ET treatment provides the first known intervention resulting in the modulation of inositol trisphosphate-dependent Ca2+ release.

Serum levels of Etretinate (Ro 10-9359) and its metabolite (Ro 10-1670).

ABSTRACTSerum levels of Etretinate (ET, Ro 10‐9359) and its metabolite (AM, Ro 10‐1670) were monitored during and after cessation of ET treatment in 12 patients with acquired disorders of keratinization who underwent the ET therapy at initial doses of 30 to 60 mg/day. Studies were made of the possible correlations between ET and AM serum levels, the appearance and disappearance of side effects, and elimination time profiles. Side effects appeared 1 to 2 weeks after the initiation of ET administration in all cases, although serum ET and AM levels at this time varied considerably, indicating individual differences in ET and AM susceptibility in the appearance of side effects. Serum ET and AM levels at the time of disappearance of side effects were lower than those at the time of appearance, suggesting some correlation of side effects with serum levels of ET, AM, or both. Serum level curves for ET and AM after cessation of ET administration were diverse. The maximum ET and AM elimination times from serum were 3 and 6 months, respectively.

An Extended Version of a Conceptual Model for Evaluating Annual Nitrogen Leaching Losses from Croplands

AbstractPreviously, a steady‐state conceptual N model was applied to corn (Zea mays L.) field trials at two University of California Field Stations. That model examined only the inputs and outputs of N into a soil‐plant‐water system without considerations of carryover inorganic soil N and mineralization of organic soil N. It predicted N leaching losses reasonably well in the corn plots at the Kearney site where residual soil N was low, but not for the Davis site where considerable mineralization of soil organic N occurs.This steady state model was extended so that it would be applicable to the transient conditions prevailing at the Davis site. The revisions included provisions for the presence of residual inorganic soil N and the mineralization of organic soil N as well as inputs of organic N such as manures and sewage sludges and their mineralization rates. The original water submodel was not modified. The model is described in the appendix and required input parameters with examples are listed.The revised model was tested with 2 years of corn field trials at Davis which consisted of four (NH4)2SO4 rates (0, 90, 180, and 360 kg N/ha) and three irrigation regimes (1/3, 3/3, and 5/3 of the corn evapotranspiration). Sensitivity analysis evaluated the importance of the harvested crop coefficient, the denitrification coefficient, and the mineralization rate constant for organic soil N, and aided in estimating the latter two experimentally unmeasured parameters.Computed results compared favorably with measured N content in the harvested (grain and stover) crop, the residual inorganic soil N after harvest, and the average annual N concentration in the soil solution beneath the root zone at the 3‐m depth. There was no leaching of N in the 1/3 ET treatment; from 0.5 to 12 kg N/ha per year N leaching losses in the 3/3 ET treatment; and from 13 to 144 kg N/ha N leaching losses in the 5/3 ET treatments. Some differences were noted in the annual leaching losses between the 1975 and 1976 corn crops in the 5/3 and 3/3 ET treatments mainly due to differences in seepage out of the root zone.It is concluded that the applicability and utility of this expanded model have been significantly enhanced over that of the previous steady‐state model.