Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure

Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure. Available data indicate that B cell proliferation is inhibited in chronic renal failure and this is due to excess blood levels of PTH. This defect may also affect immunoglobulin production. We examined production of IgG, IgM and IgA by B cells stimulated with Staphylococcus aureus Cowan I (SAC) or with pokeweed mitogen (PWM) after eight days of culture and evaluated the effect of PTH on this process in 34 hemodialysis patients and 44 normal subjects. IgG, IgM and IgA production by B cells from patients was lower (P < 0.01) than by B cells from normal subjects. Both 1-34 and 1-84 PTH inhibited (P < 0.01) immunoglobulin production by B cells from normal subjects and dialysis patients. However, this inhibitory effect was evident in dialysis patients only with the higher dose of PTH. The inhibition of immunoglobulin production by PTH occurred only when the hormone was added at the initiation of the B cell culture. Inactivation of PTH abolished its inhibitory effect on immunoglobulin production. Agents that stimulate cAMP production (forskolin, cholera toxin) and the cAMP analogue, 8-bromoadenosine 3′,5′ cyclic monophosphate inhibited immunoglobulin production by B cells from both normal and dialysis patients, and the degree of inhibition was not different between the two groups. The calcium inophore A23187 also inhibited IgG, IgA and IgM production by B cells from normal subjects and dialysis patients; there was no significant difference in the degree of inhibition between the two groups. The resting levels of cytosolic calcium in B cells of dialysis patients was significantly (P < 0.01) higher than that of B cells from normal subjects. The data show that: (1) immunoglobulin production is impaired in dialysis patients; (2) B cells of dialysis patients have elevated resting levels of cytosolic calcium; (3) PTH inhibits IgG, IgA and IgM production and this effect is at least partly mediated by PTH-induced cAMP production and alterations in cytosolic calcium into B cells; (4) this inhibitory effect is mediated by events that affect initial stages of B cell proliferation and maturation; (5) the requirement for high dose of PTH for its inhibitory effect on B cells from dialysis patients is probably due to desensitization and/or down-regulation of PTH receptors on B cells. The results are consistent with the proposition that impaired immunoglobulin production by B cells from dialysis patients is at least partly due to the state of secondary hyperparathyroidism in these patients

Remarks on the Cauchy functional equation and variations of it

This paper examines various aspects related to the Cauchy functional equation $f(x+y)=f(x)+f(y)$, a fundamental equation in the theory of functional equations. In particular, it considers its solvability and its stability relative to subsets of multi-dimensional Euclidean spaces and tori. Several new types of regularity conditions are introduced, such as a one in which a complex exponent of the unknown function is locally measurable. An initial value approach to analyzing this equation is considered too and it yields a few by-products, such as the existence of a non-constant real function having an uncountable set of periods which are linearly independent over the rationals. The analysis is extended to related equations such as the Jensen equation, the multiplicative Cauchy equation, and the Pexider equation. The paper also includes a rather comprehensive survey of the history of the Cauchy equation.Comment: To appear in Aequationes Mathematicae (important remark: the acknowledgments section in the official paper exists, but it appears before the appendix and not before the references as in the arXiv version); correction of a minor inaccuracy in Lemma 3.2 and the initial value proof of Theorem 2.1; a few small improvements in various sections; added thank

The impact of diabetes on the pathogenesis of sepsis

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones