Effect of combination therapy with cimetidine and pirenzepine on plasma parathyroid hormone and calcitonin levels in hemodialyzed patients

Summary In this study we evaluated the effects of an oral combination therapy with cimetidine and pirenzepine on plasma parathyroidhormone (PTH) and calcitonin (CT) levels in 24 patients on maintenance hemodialysis (mean age: 50 years; mean duration of dialysis treatment: 23 months). As compared to the pre-treatment plasma levels of PTH and CT, there were no significant changes of their plasma concentrations during a 4-week administration of 800 mg cimetidine or 100 mg pirenzepine daily, and the concentrations also did not change significantly during the following 4 weeks of combination therapy with cimetidine and pirenzepine in the above mentioned dosage. Serum concentrations of calcium and phosphate and the activity of the alkaline phosphatase showed no significant changes either. Therefore, we suggest that this therapeutic approach cannot be considered for the treatment of uremic hyperparathyroidism.     

Therapeutic efficacy of combined -receptor-antagonists on severe histamine-induced cardiovascular reactions in humans

Histamine is a well known causal factor in a variety of clinical events and complications, especially in allergic and anaphylactoid reactions. We therefore investigated whether a dose-dependent therapeutic effect of H₁+H₂-antagonists (dimethindene maleate+cimetidine) could be shown in the treatment of a histamine-induced cardiovascular reactions in humans. 6 healthy male volunteers participated in a randomized single-blind crossover-study. A histamine dosage leading to a decrease of the mean arterial pressure to 60 mmHg within 2 min was continuously infused over a period of 15 min on two occasions. The volunteers received either histamine+saline or histamine+treatment first. Treatment started 3 min after the start of the histamine infusion (4 mg dimethindene maleate+200 mg cimetidine i.v.) and was repeated every 2 min until the cardiovascular baseline values were reached or 15 min were completed. Statistical analysis of the treatment effect was performed on an intraindividual basis (ANOVA) withp<0.05 In both treatment courses mean MAP decreased to about 60 mmHg. While in the saline group MAP remained at this low level during the time of histamine infusion, all volunteers quickly responded to treatment with dimethindene maleate+cimetidine. After 8 mg dimethindene maleate+400 mg cimetidine MAP reached baseline values in all volunteers (p<0.01). Mean HR increased to 119 bpm in the saline group after 3 min. Treatment with dimethindene maleate+cimetidine showed similar efficacy against histamine-induced tachycardia (p<0.01). It may thus be concluded that usual dosages of H₁- and H₂-receptor-antagonists are effective in the treatment of histamine-induced cardiovascular reactions.

     

Parathyroid hormone concentrations during and after two periods of high intensity exercise with and without an intervening recovery period

The purpose of this study was to examine the effect of a recovery period between two periods of exercise on bone metabolism and related hormones. Concentrations of serum parathyroid hormone ([PTH]), plasma ionized calcium ([Ca²⁺]) and total calcium were measured. A group of 12 healthy men aged 20–27 years participated in this study. They took part in two exercise protocols (P₁ and P₂) on two separate weeks. The exercise in P₁ comprised two successive periods of 21 min each at 70% and 85% of maximal oxygen uptake; P₂ comprised two periods of exercise at the same intensities but separated by 40 min of recovery. Venous blood samples were collected 1 day before the sessions (control), before each protocol, during (7th and 21st min), at the end (42nd min in P₁ and 82nd min in P₂) and after 24 h of recovery. The [PTH] was significantly elevated during the two protocols (P<0.01), remained raised in P₁ after 24 h of recovery (P<0.05) and was significantly lower (P<0.01) at the end of P₂ when compared to P₁. The [Ca²⁺] decreased significantly during and at the end of the two protocols (P<0.01) and had returned to control values after 24 h of recovery. Plasma lactate concentration increased during the two protocols (P<0.01) and returned to control values after recovery. These results indicate firstly that [Ca²⁺] decreases during continuous exercise as [PTH] increases and remains raised after 24 h of recovery, secondly that a recovery period between two periods of exercise attenuates the variations in [Ca²⁺] and [PTH], and thirdly that recovery may have anabolic effects on bone. However, the small physiological changes observed prevent us from forming any firm conclusion about this. Electronic Publication     

Therapeutic efficacy of combined -receptor-antagonists on severe histamine-induced cardiovascular reactions in humans

Histamine is a well known causal factor in a variety of clinical events and complications, especially in allergic and anaphylactoid reactions. We therefore investigated whether a dose-dependent therapeutic effect of H₁+H₂-antagonists (dimethindene maleate+cimetidine) could be shown in the treatment of a histamine-induced cardiovascular reactions in humans. 6 healthy male volunteers participated in a randomized single-blind crossover-study. A histamine dosage leading to a decrease of the mean arterial pressure to 60 mmHg within 2 min was continuously infused over a period of 15 min on two occasions. The volunteers received either histamine+saline or histamine+treatment first. Treatment started 3 min after the start of the histamine infusion (4 mg dimethindene maleate+200 mg cimetidine i.v.) and was repeated every 2 min until the cardiovascular baseline values were reached or 15 min were completed. Statistical analysis of the treatment effect was performed on an intraindividual basis (ANOVA) withp<0.05 in=" both=" treatment=" courses=" mean=" map=" decreased=" to=" about=" 60=" mmhg.=" while=" in=" the=" saline=" group=" map=" remained=" at=" this=" low=" level=" during=" the=" time=" of=" histamine=" infusion,=" all=" volunteers=" quickly=" responded=" to=" treatment=" with=" dimethindene=" maleate+cimetidine.=" after=" 8=" mg=" dimethindene=" maleate+400=" mg=" cimetidine=" map=" reached=" baseline=" values=" in=" all=" volunteers=">p<0.01). mean=" hr=" increased=" to=" 119=" bpm=" in=" the=" saline=" group=" after=" 3=" min.=" treatment=" with=" dimethindene=" maleate+cimetidine=" showed=" similar=" efficacy=" against=" histamine-induced=" tachycardia=">p<0.01). it=" may=" thus=" be=" concluded=" that=" usual=" dosages=" of=">₁- and H₂-receptor-antagonists are effective in the treatment of histamine-induced cardiovascular reactions.     

Long-term management of duodenal ulcer with pirenzepine and cimetidine: a double-blind controlled clinical trial

The effectiveness of pirenzepine in the prevention of duodenal ulcer relapses was assessed by means of a double-blind controlled trial versus cimetidine. Seventy duodenal ulcer out-patients endoscopically healed after a 6-week treatment with either pirenzepine or cimetidine were admitted to the trial. The former pirenzepine patients were treated again with pirenzepine: 1 tablet at breakfast and 2 tablets at bedtime (75 mg daily). The former cimetidine patients were treated again with cimetidine: 2 tablets at bedtime (400 mg daily). They received one placebo tablet at breakfast. Both treatments lasted 12 months. Tablets of a mild antacid were permitted only if necessary to relieve severe ulcer pain and heartburn. Patients underwent clinical and endoscopic assessments after 4, 8 and 12 months of treatment and whenever ulcer symptoms lasted more than 4-5 consecutive days. Only 47 out of the 70 patients that entered the trial underwent all clinical and endoscopic controls. Sixteen out of 23 patients on pirenzepine (70%) and 17 out of 24 patients on cimetidine (71%) did not relapse after 12 months. The difference is not statistically significant. Both treatments were well tolerated. The results show that pirenzepine was as effective as cimetidine in the prevention of duodenal ulcer relapses when administered at a dosage of 75 mg daily (of which 50 mg at bedtime) for one year.     

Histamine-mediated regulation of cAMP levels and inositol phosphate metabolism in isolated rabbit retina

In pieces of the rabbit retina, histamine (HI) had no significant effect on cAMP accumulation; however, HI inhibited forskolin-evoked accumulation of the nucleotide. Mepyramine (H₁-antagonist) was without effect, while cimetidine (H₂-antagonist) antagonized the HI action. Dimaprit (H₂-agonist) mimicked the HI action, however its action was not significantly affected by H₂-antagonists. Since phosphodiesterase (PDE) inhibitors prevented the HI action it is suggested that HI-induced inhibition of the forskolin effect results from HI-induced activation of cAMP breakdown. The muscarinic agonist carbachol, and to a lesser extent HI, both increased [³H]inositol incorporation and intensified accumulation of [³H]inositol phosphates in the rabbit retina.     

The effect of cimetidine on platelet function: a study involving gastric fluid measurements

Summary Gastric fluid samples were aspirated 30 and 60 minutes after the ingestion of two 200 mg tablets of cimetidine. The concentration of cimetidine in these samples was measured and their effect on platelet aggregation assessedin vitro. Gastric fluid samples significantly inhibited adrenaline- and ADP-induced platelet aggregationin vitro. In a further series of experiments, cimetidine solutions, at concentrations found in gastric fluid, inhibited platelet aggregation and thromboxane A₂ (TXA₂) release,in vitro. Ranitidine, another H₂-receptor antagonist, was a more potent inhibitor of platelet aggregation than cimetidine. Since ranitidine is also the more potent H₂-receptor antagonist which, unlike cimetidine, does not include an imidazole group (which is known to inhibit TXA₂ synthesis) in its structure, we conclude that H₂ blockade mediates the observed inhibition of aggregation. This platelet anti-aggregatory effect may be relevant to haemostatic mechanisms involved in bleeding peptic ulcers or gastric erosions exposed to high local concentrations of H₂-receptor antagonists.     

Effect of in vivo exposure to insulin on glucose metabolism in rat aorta

The effect of administration of insulin in vivo on accumulation of [14C]glucose carbon in rat aorta in vitro was studied. Insulin was injected intravenously in a tail vein 5-60 min before the rats were killed and the accumulation of [14C]glucose was determined after incubation for 30-120 min in 5.6 mM [14C]glucose. When determined 30 min after injection of insulin (4 U kg-1) the aortic [14C]glucose incorporation was significantly increased when an incubation period of 120 min was used, while no significant effect was found after incubation for 30 or 60 min. In subsequent experiments an incubation time of 120 min was used. The aortic [14C]glucose accumulation was not increased when determined 5 or 60 min after injection of insulin (4 U kg-1). Injection of insulin (2 U kg-1) 5 or 30 min before the rats were killed had no effect on the aortic [14C]glucose accumulation but it had a pronounced effect on [14C]glucose accumulation in rat diaphragm. Serum insulin determined 30 min after injection of insulin (2 U kg-1) was 731 +/- 58 mU-1 and in saline-treated control rats 37 +/- 3 mU l-1. These results suggest that the glucose metabolism of vascular smooth muscle has a low sensitivity to the immediate effects of insulin.     

Moderate endurance training has no effect on the parathyroid function of heart transplant patients

The benefit of retraining for heart transplant recipients (HTR) is now well established. The rehabilitation of these patients can be compromised by osteopenia and bone fractures. The resting levels of parathyroid hormone (PTH) and exercise-induced increases are higher in HTR than in healthy controls. To evaluate the effect of a moderate endurance training programme on parathyroid activity, six HTR, an average of 18 months after transplant, and seven healthy sedentary controls have been studied. None of the subjects had a history of bone disease. Two exercise tests (square wave endurance exercise tests, SWEET) with identical work rates were performed before and after training. Intact PTH, ionized calcium (Ca²⁺), phosphorus (Pi) and pH were measured at rest, during exercise and in the recovery periods. Training consisted of a 45-min SWEET three times a week for 6 weeks. Levels of Ca²⁺, Pi and PTH showed a significant increase during the exercise session in both groups. Ca²⁺ and Pi levels decreased rapidly after the cessation of exercise whereas PTH reached a peak at the 10th min of the recovery in both groups. This increase in PTH was significantly higher in HTR than in controls. However, despite a significant improvement of total endurance work (+28% in HTR, +29% in controls) this endurance training had no effect on resting levels of PTH, plasma Ca²⁺ or Pi, nor on their exercise-induced variations. The exercise-induced decrease in pH was less pronounced after training which is evidence of training. We conclude that a short endurance training programme does not alter the moderate hyperparathyroidism of HTR. The effect of such a training programme on bone mass and bone mineral density needs now to be evaluated. Accepted: 4 February 1997     

RPE-lactate dissociation during extended cycling

This study examined the association of blood lactate concentration [La] and heart rate (HR) with ratings of perceived exertion (RPE) during 60 min of steady workload cycling. Physically active college-aged subjects (n=14) completed an exhaustive cycling test to determine VO_{2 peak} and lactate threshold (2.5 mmol l^–1). Subjects then cycled for 60 min at the power output associated with 2.5 mmol l^–1 [LA]. HR, [LA], RPE-overall, RPE-legs and RPE-chest were recorded at 5, 10, 20, 30, 40, 50 and 60 min. The 60-min trials were below maximal lactate steady state, with peak lactate concentration occurring at 20 min after which [LA] declined. The 20-min point was therefore considered pivotal, and data at other points were compared to this time point. Repeated measures ANOVA with simple contrasts (alpha=0.05) showed (a) [LA] at 40, 50 and 60 min was significantly lower than at 20 min, (b) RPE-O and RPE-L were significantly greater at 30, 40, 50 and 60 min than at 20 min, (c) RPE-C was significantly greater at 40, 50 and 60 min than at 20 min, and (d) HR was significantly greater at 30, 40, 50 and 60 min than at 20 min. Significant (P<0.05) positive correlations were found between HR and RPE-O (r=0.43), RPE-L (r=0.48) and RPE-C (r=0.41) while correlations for [LA]-HR (r=0.13) and [LA]-RPE (RPE-O: r=–0.11, RPE-L: r=0.01, RPE-C: r=–0.06) were weak and non-significant. There is a dissociation of RPE and [LA] owing to RPE drift and lactate kinetics in longer duration sub-maximal exercise. Apparently, [LA] is not a strong RPE mediator during extended cycling.     

The role of histamine in wound healing. II. The effect of antagonists and agonists of histamine receptors (H1 and H2) on collagen levels in granulation tissue

The effects of mepyramine (H₁-receptor antagonist), cimetidine (H₂-receptor antagonist), IEM-813 (H₁-receptor agonist) and 4-Met-Hi (H₂-receptor agonist) on collagenogenesis processes in subcutaneous implanted sponges of rats were studied. Administration into sponges of cimetidine 30 min before histamine injection blocked both the stimulatory effect of low histamine doses and the inhibitory effect of high histamine doses on collagen formation. Low doses of 4-Met-Hi increased collagen levels but reduced the levels at high doses. Mepyramine and IEM-813 did not influence collagen biosynthesis.     

Expired air temperature during prolonged exercise in cool- and hot-humid environments

The purpose of this investigation was to measure expired air temperature under cool- and hot-humid environmental conditions at rest and during prolonged exercise to: (1) establish if significant increases in body core temperature affected expired air temperature, and (2) to determine if the temperature setting for heating the pneumotachometer in an open-circuit system requires adjustment during prolonged exercise tests to account for changes in expired air temperature. Six male distance runners completed two tests in cool-humid [dry bulb temperature (T _db) 15.5 (SD 1.3)°C, wet bulb temperature (T _wb) 12.1 (SD 1.4)°C] and hot-humid [T _db 31.6 (SD 0.6)°C, T _wb 24.9 (SD 0.6)°C, black globe temperature (T _g) 34.3 (SD 0.3)°C] environments, running at a velocity corresponding to 65% [67.1 (SD 2.82)%] of their maximal oxygen uptake. Rectal temperature and expired air temperatures were compared at rest, and after 30 min and 60 min of exercise for each environment. The main finding of this investigation was a significant (P?相似文献   

Pirenzepine does not impair liver blood flow in the rat

The present study was performed with the aim of establishing whether the muscarinic-receptor antagonist pirenzepine impairs liver blood flow, as previously observed for H2-blockers. For this purpose, two different doses of pirenzepine (0.3 and 0.6 mg/100 g b.w. respectively) were administered to two groups of rats. Liver plasma flow was measured 30 min after treatment by the new sorbitol clearance test which is simple and does not require hepatic vein catheterization. The results were compared with those obtained in a control group and in a group treated with cimetidine. It was shown that, compared to the control group in which the observed functional liver plasma flow was 5.0 +/- 1.3 ml/min/100 g b.w. (MV +/- SD), rats treated with either dose of pirenzepine showed no significant impairment of liver perfusion. On the other hand, cimetidine treatment produced a significant reduction (p less than 0.001) of functional liver plasma flow. Our results show that pirenzepine treatment does not significantly impair liver functional activity through reduced liver perfusion. They also suggest that muscarinic receptors are probably not involved in the control of splanchnic blood flow.     

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism

BackgroundNormocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients.MethodsA total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122).ResultsNPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions.ConclusionWe found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.     

Mitt-C-regionales Parathormon in der klinischen Routine: Diagnostische Wertigkeit beim extrarenalen (primären) und renalen (sekundären) Hyperparathyreodismus

Summary The selective determination of mid-C-regional parathyroid hormone (mid-C-PTH) in combination with other laboratory parameters is a reliable tool for diagnosis and treatment of extrarenal (primary) and renal (secondary) hyperparathyroidism. Early stages, which show either high-to-normal serum calcium and elevated mid-C-PTH or increased serum calcium but normal mid-C-PTH, can be distinguished from overt hyperparathyroidism. Alkaline phosphatase (AP) activity and mid-C-regional PTH provide biochemical confirmation of histologically classified renal osteodystrophy. Since the index AP×PTH signifies osseous changes in dialysis patients at an early stage, therapeutic regimens may be altered without additional invasive procedures. After renal transplantation mid-C-PTH normalizes and serum creatinine decreases. Increased mid-C-PTH in patients with normal renal graft function reflects autonomous PTH secretion, which requires careful monitoring to prevent PTH-induced hypercalciuria.

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Abkürzungsverzeichnis AP Alkalische Phosphatase - Ca Gesamtcalcium - DFO Desferrioxamin - HPT Hyperparathyreodismus - Index (AP×PTH) Produkt aus Mitt-C-PTH und AP - Mitt-C-PTH Mitt-C-regionales PTH - MW Molekulargewicht - NTX Nierentransplantation - PTH Parathormon - PTX Parathyreoidektomie mit Reimplantation in den Unterarm - PO₄ Phosphat - RIA Radioimmunoassay Mit Unterstützung der Deutschen Forschungsgemeinschaft (DFG) Ju 177/1-1     

Fluid balance and renal response following dehydrating exercise in well-trained men and women

We examined the recovery of plasma volume, plasma osmolality, renal water and sodium handling and fluid-regulating hormones to dehydrating exercise in well-trained women and compared them to men. Ten male and eight female athletes cycled at anaerobic threshold at an ambient temperature of 32°C until dehydration by 3 % of their body mass (Mb). After exercise, they drank water equal to 1 % Mb and rested for 240 min. Plasma renin activity (PRA), serum aldosterone [ALDO]_s, plasma arginine vasopressin [AVP]_pl, norepinephrine concentrations and plasma osmolality (Osm_pl) were determined at baseline, end of exercise, 30, 60, 120 and 240 min postexercise. Urine was collected at baseline, end of exercise, 60, 120 and 240 min postexercise. Renal free water and sodium handling were assessed. The recovery of OSM_pl and plasma volume occurred within the first 60 min of recovery and at similar rates between the groups. However, women had lower PRA at the end of exercise (P = 0.05), an earlier recovery of [ALDO]_s, and a slower [AVP]pl recovery. Overall fluid balance was similar between the men and women, as were the early recovery of renal free water clearance (C _{H 2}O). During the last 120 min of recovery C _{H 2}O was more negative (greater water reabsorption) and fractional sodium excretion was increased in the women compared to the men. Despite small differences in sodium and water reabsorption following dehydration, it appears from other study that recovery from dehydrating exercise in well-trained men and women is remarkably similar.     

Lipolytic responses induced by intracerebroventricular administration of histamine in the rat

Histamine (10–50 g) administered intraventricularly in conscious rats induced an increase in serum-free fatty acids. The maximum, significant increase appeared 30–60 min after administration. Histamine H₁-receptor antagonists, mepyramine and chloropyramine, when injected 2 h prior to histamine, abolished considerably hyperlipaemic responses to histamine. H₂-Receptor antagonists, metiamide and cimetidine, given i.c.v. only moderately diminished the histamine-induced hyperlipaemia. Histamine injected i.c.v. also increased serum corticosterone levels considerably. This elevation was prevented significantly by the H₁-receptor antagonist, mepyramine, but not by the H₂-receptor blocker, cimetidine. It seems likely that histamine given i.c.v. induces lipolysis through the release of ACTH, one of the known lipid-mobilizing hormones. The central lipid-mobilizing mechanism after histamine depends more on activation of H₁- than H₂-receptors.     

Altered Phospholipid Metabolism in Escherichia coli Accompanying Killing by Disrupted Granulocytes

The effect of bactericidal concentrations of disrupted rabbit granulocytes and of partially purified granulocyte fractions on phospholipid metabolism by Escherichia coli has been investigated. Previous studies in this laboratory have shown that, during and after killing of E. coli by granulocytes, bacterial macromolecular synthesis continues. Similarly, despite almost complete loss of viability within 15 min, incorporation of [1-¹⁴C]palmitate, [2-¹⁴C]glycerol, and [1-¹⁴C]acetate into E. coli phospholipids, in the presence of granulocyte preparations, remains the same as in control E. coli populations for at least 1 h. Incorporation of [1-¹⁴C]oleate into E. coli phospholipids is actually stimulated during the first 60 min of incubation in the presence of granulocyte preparations (more than twofold at 30 min and 40% at 60 min). With all labeled lipid precursors, bactericidal granulocyte preparations cause a relative increase in the labeling of E. coli cardiolipin, with a corresponding drop in labeled phosphatidyl-glycerol. Labeled lyso-compounds accumulate in the presence of granulocyte preparations when [1-¹⁴C]palmitate, but not when [1-¹⁴C]oleate is the labeled precursor. Since oleate occurs mainly in the 2-acyl position of E. coli phospholipids, whereas at least 50% of palmitate occurs in the 1 position, it appears that a phospholipase A₂ acts on the E. coli phospholipids. These various effects are also seen when E. coli are exposed to highly purified granulocyte preparations that possess potent bactericidal and phospholipase A₂ activities. We speculate that this phospholipase A₂ in the granulocyte preparations stimulates oleate but not palmitate incorporation by initiating increased turnover of the fatty acid in the 2-acyl position of E. coli phospholipids, causing formation of 1-acyl lyso-compounds likely to be preferentially reacylated with unsaturated fatty acids.     

Calcium-phosphorus homeostasis and changes in parathyroid hormone secretion in cats with various stages of spontaneous chronic renal failure

Feline chronic renal failure was recognized with increased frequency in Maine coon, Abyssinian, Siamese, Russian blue, and Burmese cats. The objective of this study was to investigate the relationship between parathyroid hormone (PTH) level, calcium, and phosphorus homeostasis and the development of various stages of the naturally occurring chronic renal failure (CRF) in cats. Thirty-two CRF cats without history of receiving special diet for renal diseases that were presented to the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University were studied. Nineteen CRF cats were followed prospectively for 60 days and divided into two groups: uremic group (11 cats) and end-stage group (eight cats). The control group (13 cats) were normal cats, which were brought for vaccination at the same hospital within the same period. CRF cats with blood urea nitrogen concentrations of more than 50 mg/dl, serum creatinine level of more than 2.1 mg/dl, and urine specific gravity of between 1.008 and 1.014 were included into the study. Completed blood count, blood chemistry, electrolytes, including sodium, potassium, total calcium, and phosphorus, and PTH levels were measured on days 0, 14, 30, and 60 after the first diagnosis. The results showed that cats with CRF had significantly lower red blood cells, hemoglobin, and pack cell volume than control cats (p < 0.01) on days 0, 14, 30, and 60. PTH levels on first day of diagnosis were 50.51 ± 19.65, 79.41 ± 28.12, and 183.37 ± 50.12 pg/ml in controls, uremic, and end-stage groups, respectively. Cats in end-stage group had significantly increased levels of PTH when compared to control (p < 0.01) and uremic groups (p < 0.05) on days 0, 14, and 30. Serum phosphorus levels also increased significantly in end-stage group (p < 0.001), indicating the presence of renal secondary hyperparathyroidism. This study reveals that PTH level is significantly increased in end-stage CRF cats who did not received special diet for renal diseases. The development of renal secondary hyperparathyroidism in end-stage CRF cats significantly decreased its survival rate.     

Fluoride interactions with stimulus-secretion coupling of normal and pathological parathyroid cells

Effects of the GTP binding protein (G-protein) activator NaF on parathyroid hormone (PTH) release, cytoplasmic Ca²⁺ concentration ([Ca²⁺]₁) and cAMP content of bovine as well as normal and pathological human parathyroid cells were studied using precautions to avoid CaF₂ precipitation. In 0.5 mm external Ca²⁺, NaF inhibited PTH release and lowered the cAMP content by 50–70% of the effects attained with 3.0 mm Ca²⁺. The NaF-induced increase of [Ca²⁺]₁ was considerably smaller than that obtained with rise of external Ca²⁺. It seems likely that NaF activates the inhibitory G_i-protein involved in the regulation of cAMP generation. However, it is unclear whether the sluggish rise of [Ca²⁺]₁ induced by NaF is due to a direct effect of a G-protein on Ca²⁺ entry, or somehow related to the G-protein mediated formation of inositol 1,4,5-trisphosphate, which is part of the signal transduction pathway normally initiated by Ca²⁺ binding to its receptor on the parathyroid cell surface. Inhibition of PTH release by NaF probably results from the combined effects on [Ca²⁺]₁ and cAMP content. In hyperparathyroidism (HPT) the actions of NaF were not markedly affected despite severe impairments of Ca²⁺-inhibited PTH release and Ca²⁺ triggered increase of [Ca²⁺]₁. Consistent with observations of down regulation of the parathyroid Ca²⁺ receptor in HPT, the present results indicate that the disease perturbs signal transduction at a level proximal to the site of action for NaF.