The salt paradox of the early diabetic kidney is independent of renal innervation.

Glomerular filtration rate (GFR) is inversely and thus paradoxically related to dietary NaCl intake in rats and patients with early type 1 diabetes mellitus (DM). Enhanced sensitivity of proximal reabsorption to NaCl diet inducing secondary adaptations in GFR through actions of tubuloglomerular feedback causes this salt paradox. We studied the role of renal nerves for the salt paradox in rats with streptozotocin (STZ)-induced DM since a regulatory influence of renal nerves on proximal reabsorption is well established. The left kidney (LK) was denervated before induction of STZ-DM. Subsequently, the normal diet was continued or a low NaCl diet was initiated and 1 week later animals were prepared for clearance experiments under anesthesia including ureter catheterization to measure GFR for each kidney. In diabetic rats, the right innervated as well as the left denervated kidney showed higher values for GFR and kidney weight in animals on a low versus a normal NaCl diet indicating that the salt paradox occurs independent of renal innervation. In addition, evidence is provided that the renal nerves of non-diabetic rats do not contribute to renal Na(+) retention during dietary NaCl restriction but modulate renal hemodynamics and kidney weight under these conditions.

Urinary dopamine excretion in healthy volunteers: effect of sodium diet and acute water load.

The present study was designed to investigate, in human subjects, urinary dopamine excretion under different conditions of sodium and water homeostasis. In a cross-over trial, ten healthy volunteers were subjected to low-salt (LS; dietary salt restriction, sodium chloride (NaCl) intake <5 g per day), normal-salt (NS; normal food ad libitum), and high-salt (HS; normal food plus NaCl 100 mg/kg per day) regimens for 8 days in a randomized order. On day 7, urine was collected for 24 h. The variations in urinary sodium excretion reflected the dietary salt intake (LS: 16.3+/-4.7; NS: 144.1+/-18.2; HS: 221.9+/-12.9 mmol 24 h(-1) 1.73 m(-2)), but were not accompanied by significant changes in urinary dopamine excretion. On day 8, clearance studies showed that an acute oral water load of 1500 ml did not alter glomerular filtration rate or renal plasma flow but significantly increased urinary flow rate without affecting dopamine excretion. Assuming that excreted dopamine is not metabolized or reabsorbed during the tubular passage, both the unchanged urinary dopamine output in spite of 14-fold variations in sodium excretion and its independence of an acute water load argue against the hypothesis that dopamine in the tubular lumen acts as a natriuretic and/or diuretic factor in humans.

Clinical, biochemical and immunological effectiveness of diacetyl-splenopentin (BCH 069) in hay fever.

Diacetyl-splenopentin (BCH 069) is a new pentapeptide of splenin modified by twofold acetylation. BCH 069 has thymopentin-like activity demonstrated by in vivo animal and in vitro human studies. Two groups of patients received 50 mg BCH 069 and placebo, respectively, by subcutaneous injection 3 times weekly for 4 weeks. The third group of patients received 50 mg BCH 069 by intravenous injection 3 times weekly for 6 weeks. The therapy was carried out during the peak of the pollen season. BCH 069 intravenous treatment was found to be significantly superior to placebo treatment in reducing clinical symptoms. Biochemical inflammatory signs were not observed. No increase of bronchomotoric reactivity was established in comparison to the placebo group. There was a significantly lower increase in gras-spollen specific IgE and IgG4 in the intravenous group of BCH 069. Subcutaneous therapy with BCH 069 was not effective. The study demonstrated that BCH 069 used intravenously induces clinical improvement in patients suffering from hay fever. Thus the possibility to influence hyperreactive conditions of the immune system has been confirmed. The study indicates that various application routes of BCH 069 have different effects on the immune system.

[Disease-specific and non-specific seasonal parameter changes in hayfever patients]. / Krankheitsspezifische und -unspezifische saisonale Parameterveränderungen bei Pollinosepatienten.

10 patients have been treated by subcutaneous injections of placebo three times weekly for 4 weeks within a phase-I trial of BCH-069. Immunological, hematological and biochemical parameters were observed at different times: preseasonal, seasonal and postseasonal. --Some new observations are reported, which are induced by the seasonal inflammation. For example there was a strong increase of C-reactive protein and also an increase in the triglyceride level. --The parameters could be useful for trials of new antiallergic drugs in hay fever in the future.