The renal handling of parathyroid hormone. Role of peritubular uptake and glomerular filtration

The mechanisms of uptake of parathyroid hormone (PTH) by the kidney was studied in anesthetized dogs before and after ureteral ligation. During constant infusion of bovine PTH (b-PTH 1-84), the renal arteriovenous (A-V) difference for immunoreactive PTH (i-PTH) was 22+/-2%. After ureteral ligation and no change in renal plasma flow, A-V i-PTH fell to 15+/-1% (P < 0.01), indicating continued and significant uptake of i-PTH at peritubular sites and a lesser role of glomerular filtration (GF) in the renal uptake of i-PTH. Since, under normal conditions, minimal i-PTH appears in the final urine, the contribution of GF and subsequent tubular reabsorption was further examined in isolated perfused dog kidneys before and after inhibition of tubular reabsorption by potassium cyanide. Urinary i-PTH per 100 ml GF rose from 8+/-4 ng/min (control) to 170+/-45 ng/min after potassium cyanide. Thus, i-PTH is normally filtered and reabsorbed by the tubular cells. The physiological role of these two mechanisms of renal PTH uptake was examined by giving single injections of b-PTH 1-84 or synthetic b-PTH 1-34 in the presence of established ureteral ligation. After injection of b-PTH 1-84, renal A-V i-PTH was 20% only while biologically active intact PTH was present (15-20 min). No peritubular uptake of carboxyl terminal PTH fragments was demonstrable. In contrast, after injection of synthetic b-PTH 1-34, renal extraction of N-terminal i-PTH after ureteral ligation (which was 13.4+/-0.6% vs. 19.6+/-0.9% in controls) continued for as long as i-PTH persisted in the circulation. These studies indicate that both GF and peritubular uptake are important mechanisms for renal PTH uptake. Renal uptake of carboxyl terminal fragments of PTH is dependent exclusively upon GF and tubular reabsorption, whereas peritubular uptake can only be demonstrated for biologically active b-PTH 1-84 and synthetic b-PTH 1-34.     

Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects

These experiments were performed to determine the importance of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. Cephalic stimulation was induced by a modified sham feeding (MSF) technique, during which subjects chewed and expectorated appetizing food. The response to MSF was compared with that to gastric distention with 600 ml NaCl, glucose, or food. In addition, we measured the extent to which cephalic stimulation augments acid secretion that has been stimulated simultaneously by these other mechanisms. Our conclusions are as follows: (a) cephalic stimulation accounts for approximately one-third of the acid secreted when all mechanisms act simultaneously (food-distention plus MSF); (b) within the limits imposed by the maximal secretory capacity, the response to MSF is approximately the same, regardless of whether acid secretion is otherwise unstimulated or is stimulated simultaneously by gastric distention with NaCl, glucose, or food; and (c) gastric distention prolongs the response to cephalic stimulation.     

Scar formation and ligament healing

OBJECTIVE: To compare the efficacy of IUI husband in natural versus FSH stimulated cycles. DESIGN: Prospective, controlled study. MATERIALS AND METHODS: IUI were performed in 57 infertile couples with natural cycles, and in 16 under FSH and GnRH stimulation (Short protocol). In stimulated patients also hCG and hydrogesteron were given. Indication in both groups was idiopathic infertility. Duration of infertility and the age were comparable. Semen preparation and ovarian monitoring were the same in 2 groups. RESULTS: Three pregnancies in 57 natural IUI cycles (5.3%) and 5 out of 16 cycles in stimulated women (31.2% per cycle-with one triple pregnancy). CONCLUSION: In couples with idiopathic infertility FSH stimulation significantly increases rate of pregnancy and multiple gestation.     

Response of V79 cells to low doses of X-rays and negative pi-mesons: clonogenic survival and DNA strand breaks

Mammalian cells are hypersensitive to very low doses of X-rays (< 0.2 Gy), a response which is followed by increased radioresistance up to 1 Gy. Increased radioresistance is postulated to be a response to DNA damage, possibly single-strand breaks, and it appears to be a characteristic of low linear energy transfer (LET) radiation. Here we demonstrate a correspondence between the extent of the increased radioresistance and linear energy transfer of 250 kVp X-rays and plateau and Bragg peak negative pi-mesons. The results support our hypothesis since the size of the increased radioresistant response appears to correspond to the number of radiation induced single-strand breaks. Furthermore, since survival prior to the increased radioresistant response (< 0.2 Gy) was LET-independent, these data support the notion that the increased radioresistant response may dictate the overall survival response to higher doses. However, while these data provide further circumstantial evidence for the involvement of DNA strand breaks in the triggering of increased radioresistance, more direct conclusions cannot be made. The data are not accurate enough to detect structure in the single-strand break profiles, the production of single-strand breaks being apparently linear with dose.     

Isolation of the factor VIII-von Willebrand factor complex directly from plasma by gel filtration

A high capacity gel filtration system was developed with the purpose of isolating factor VIII (FVIII) and von Willebrand factor (vWF) directly from plasma in significantly higher yields than obtained by cryoprecipitation, the technique most commonly used to recover FVIII-vWF from human plasma. After laboratory-scale gel filtration of plasma, a FVIII-containing fraction was collected containing about 90% of FVIII in the applied plasma and with almost tenfold higher purity than that obtained by cryoprecipitation. The gel filtration step has been scaled up for use as the initial step in the manufacturing process for a FVIII preparation (Nordiate).