Somatostatin inhibits urinary cyclic AMP excretion in diabetic rats.

Short term (30 min) infusion of cyclic somatostatin (50 microgram/rat), insulin (1 U/rat) or the two together significantly suppressed urinary cyclic AMP excretion in streptozotocin-diabetic rats. While somatostatin tended to increase cyclic GMP excretion, insulin had an opposite effect in diabetic but not in normal rats. It is suggested that somatostatin suppresses cyclic AMP excretion by inhibiting directly adenylate cyclase in liver and perhaps in other organs. The possibility that suppression of urinary cyclic AMP is due to inhibition of glucagon secretion is also considered.     

The effect of pituitary-adrenal manipulations upon urinary cyclic AMP excretion in man.

The present studies demonstrate that the administration of pharmacologic amounts of ACTH is associated with small but significant increases in urinary cyclic AMP excretion and in urinary cyclic AMP/creatinine ratios which are most likely related to a release of cyclic AMP from adrenocortical tissue. Acute suppression of the pituitary-adrenal axis with dexamethasone and stimulation with metyrapone, however, is not associated with changes in urinary cyclic AMP excretion. These results suggest that physiological levels of ACTH and cortisol contribute little, if any, to the urinary excretion of cyclic AMP in man.     

Changes in nephrogenous cyclic AMP excretion and plasma cyclic AMP following treatment of hyperthyroidism

Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP/dl GF were estimated in 11 thyrotoxic patients before and after medical treatment. PcAMP concentrations were significantly higher during hyperthyroidism (2.30 +/- 0.69 vs 1.88 +/- 0.71 nmol/dl; P less than 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 +/- 0.64 vs 3.44 +/- 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 +/- 0.82 vs 1.68 +/- 1.31 mmol/dl GF; P less than 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P less than 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4/GFR declined after treatment (respectively 2.44 +/- 0.13 vs 2.33 +/- 0.08 mmol/l; P less than 0.05 and 1.18 +/- 0.29 vs 1.05 +/- 0.22 mmol/l; P less than 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.     

Seasonal variation of P-wave dispersion in healthy subjects

We studied the seasonal variability of P dispersion in 523 healthy male patients, aged 22 +/- 4 years (range, 20-26). Four seasonal 12-lead resting electrocardiograms were recorded at 2 mV/cm standardization and at 50 mm/s paper speed at intervals of three months. Electrocardiograms were recorded between the hours 10 to 12 AM. The difference between the maximum P-wave duration and minimum P-wave duration was calculated and defined as "P dispersion." There was a significant seasonal variation in the maximum P-wave duration (P = .001) and P dispersion (P = .001), with the longest maximum P-wave duration (121 +/- 16 ms) and P dispersion (41 +/- 7 ms) observed in winter and the shortest maximum P-wave duration (106 +/- 15 ms) and P dispersion (24 +/- 8 ms) observed in summer. The minimum P-wave duration did not show any significant seasonal variation. In conclusion, there exists a significant seasonal variation in the maximum P-wave duration and P dispersion in healthy patients. Seasonal variation of P dispersion resulted from the significant variation of maximum P-wave duration.     

Seasonal variation of C-reactive protein in apparently healthy Koreans

BACKGROUND: C-reactive protein (CRP) is known as an emerging recognized marker of the potential risk of myocardial infarction and stroke, and several studies have reported higher incidences of cardiovascular events during the winter months. Here, we investigated seasonal CRP variations using a high-sensitivity immunoradiometric assay in apparently healthy Koreans. METHODS: This study included 18,445 apparently healthy Koreans (12,064 men and 6381 women, 47.2 (11.5) years of age). Anthropometric indices of adiposity, metabolic variables, blood pressure (BP), and several cardiovascular risk factors were measured. High sensitivity CRP testing was performed by immunonephelometry. RESULTS: The mean (SD) CRP level in the study population was 1.66 (2.15) mg/L, and mean (SD) CRP levels in the spring, summer, fall and winter were 1.76 (2.30) mg/L, 1.51 (1.94) mg/L, 1.61 (2.08) mg/L, and 1.76 (2.30) mg/L, respectively. After adjusting for age, sex, diabetes, hypertension, regular exercise, smoking, and body mass index, the odds ratios of an elevated CRP in the spring, fall and winter season were 1.196 (95% CI, 1.024-1.396 p = 0.024), 1.086 (95% CI, 0.943-1.250 p = 0.251) and 1.258 (95% CI, 1.088-1.456 p = 0.002), respectively, as compared with the summer season. CONCLUSIONS: Our results indicate a highly significant seasonal variation in CRP levels, with higher values during winter and spring than in summer. Elevated plasma CRP levels can be related to an increased risk of cardiovascular events, which are more prominent during the winter months. To further elucidate this relationship additional studies are needed.     

Epinephrine-induced alterations in urinary cyclic AMP in hyper- and hypothyroidism.

Although ratios of urinary cyclic AMP (cAMP) to creatinine were found in this study to be elevated in hyperthyroidism, as previously reported, this elevation appears to result primarily from a decrease in the rate of urinary creatinine excretion associated with the hyperthyroid state and not to be due to an increase in the urinary cAMP production rate. Indeed, there was no significant alteration observed in the urinary cAMP excretion found in 15 hyper-, 12 eu-, and 5 hypothyroid subjects. However, a slight, but significant increase in the 24-hour urinary cAMP excretion was noted in ambulating hyperthyroid subjects (8.5 +/- 2.4 muMol/day; normal 5.2 +/- 1.6 muMol/day; P less than .05). In contrast, the effect of the infusion of 0.05 mug/kg/min of epinephrine over a 2-hour period, resulted in a significantly greater rise in urinary cAMP excretion in hyperthyroid patients (0.83 +/- 0.07 muMol/h) compared to euthyroid subjects (0.53 +/- 0.4 muMol/h; P less than .005). Furthermore, hypothyroid subjects had no significant rise in urinary cAMP excretion after epinephrine infusion (P less than .001). Cardiovascular end-organ response to the epinephrine infusion was also greater in the hyperthyroid subjects and virtually absent in the hypothyroid group. These results suggest that there may be a significant alteration in the cAMP generating systems in states of thyroid hormone excess or insufficiency, and that provocative stimuli, such as epinephrine, may have its end-organ response modified by thyroid hormone effects on adenylate cyclase-cyclic AMP generating systems.     

Urinary cyclic AMP excretion in birds: dependence on parathyroid hormone activity

The cyclic AMP response of avian kidney to parathyroid activity has been evaluated both in vitro and in vivo. The production of cyclic AMP by dispersed avian kidney cells was stimulated by bovine parathyroid hormone or by an extract of avian parathyroid glands. Intravenous infusion of bovine parathyroid hormone resulted in increased urinary excretion and plasma concentration of cyclic AMP, as well as increased plasma calcium and urinary phosphorus excretion. The increases in plasma and urinary cyclic AMP preceded those of plasma calcium and of phosphorus excretion. EDTA infusion resulted in a decrease in plasma calcium and an increase in urinary cyclic AMP excretion. After 10 days on a low-calcium diet, chickens exhibited a 4.5-fold increase in urinary cyclic AMP excretion. The results suggest that urinary cyclic AMP in chickens reflects PTH activity similar to some mammalian species.     

Effects of sodium depletion on plasma renin activity and on the urinary excretion of cyclic AMP and aldosterone in hypoparathyroid patients.

The effect of sodium depletion on plasma renin activity (PRA), urinary cyclic AMP and urinary aldosterone excretion was studied in hypoparathyroid patients whose basal urinary cylic AMP excretion (urinary cAMP) was less than 50% of that observed in normal subjects. During 7 days of sodium depletion, PRA, urinary aldosterone and urinary cAMP each rose significantly. Administration of the beta-blocker propranolol, 160 mg/day, during 5 further days of sodium depletion produced a fall in PRA and urinary cAMP, but no change in urinary aldosterone excretion. The dissociation in these effects suggests that the increase in aldosterone secretion during sodium depletion may be mediated by pathways other than the renin-angiotensin and adenyl cyclase systems. There was a high degree of correlation between PRA and urinary cAMP (P less than 0.001) during the period of sodium depletion, but not significant relationship between these parameters was found during control and propranolol phases, or in control studies in normal subjects. These findings suggest that beta-adrenergic receptors have a role in mediating the effects of sodium depletion upon renin secretion and adenyl cyclase activity.     

Circadian rhythms in the urinary excretion of cyclic 3',5'-adenosine monophosphate (cyclic AMP) and cyclic 3',5'-guanosine monophosphate (cyclic GMP) in human subjects.

Significant circadian rhythns in urinary excretion of cyclic AMP, cyclic GMP, creatinine, 17-hydroxycorticosteroids and inorganic phosphorus were demonstrated in three normal subjects (two males and one post-menopausal female) who collected serial 4-h specimens for periods of 33, 22, and 14 days, respectively. Peak excretion of the above substances occurred, respectively, at approximately 1500-1700, 2300-0200, 1700-1800, 1100-1300, and 1800-2200 h. The estimated amplitudes of the rhythms expressed as a percentage of the mean 4-h excretion rate were 12-13%, 9-13%, 9-15%, 30-78% and 22-26%, respectively. With the possible exception of cyclic GMP, all of the observed rhythms appeared to be sinusoidal, with normal periods of 24 h. The rhythms in both cyclic AMP and creatinine excretion, but not in the remaining substances may be explained largely in terms of the known rhythm in glomerular filtration rate. The factors responsible for the rhythm in cyclic GMP excretion are unknown.     

Parathyroid hormone does not increase nephrogenous cyclic AMP excretion by the dog

The renal excretion of nephrogenous cyclic AMP (NcAMP) increases in response to parathyroid hormone (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH (PTH) in man, and thereby serves as a test of parathyroid function. However, during studies of calcium-PTH interrelationships in dogs we observed no change in total urinary cAMP (UcAMP) excretion when endogenous plasma PTH levels were increased up to 10-fold. This study was designed to investigate the effects of physiologic and pharmacologic levels of PTH on NcAMP and UcAMP excretion in the dog. Maintaining plasma Ca 2 mg/dl below normal for 40 minutes caused an 8-fold increase in plasma PTH concentration, a 50% increase in the urinary fractional excretion of phosphate (FEP) but no changes in plasma cAMP levels or in UcAMP or NcAMP excretion. Infusion of a pharmacologic amount of parathyroid extract (15 U/min for 20 min) increased plasma cAMP 5-fold, UcAMP excretion 3-fold and FEP by 50% but was without effect on NcAMP excretion. We conclude that NcAMP excretion is not stimulated by PTH in the dog and thus cannot be used as an index of PTH action in vivo. The increase in UcAMP excretion by pharmacologic amounts of PTH results from glomerular filtration of increased plasma cAMP, which may be generated in bone.     

Evaluation of urinary excretion of cyclic guanosine monophosphate in clinical cardiology]

The prognostic importance of levels of urinary excretion of cyclic GMP (cGMPu), the second messenger of the atrial natriuretic factor (ANF) was studied in different cardiac pathologies in 31 patients (19 males and 12 females, average age 66 +/- 15 years) and compared with 31 control subjects of the same age (+/- 4 years) and sex. In the control group, the average cGMPu was 0.35 +/- 0.17 mumoles/24 hours/m2, and, with respect to urinary creatinine, increased with age (r = 0.54, p = 0.002). In the 16 patients with cardiac failure, the cGMPu was very high (1.03 +/- 0.59 mumoles/24 hours/m2, p less than 0.001) without any significant correlation with NYHA functional class although it fell after treatment. After myocardial infarction (8 cases including 3 with cardiac failure), the cGMPu was also high (0.49 +/- 0.33 mumoles/24 hours/m2) but it did not differ significantly from the control values in the 9 atrial arrhythmias without cardiac failure. The cGPMu was related to the cardiothoracic ratio but not to any blood gas parameter or echocardiographic measurement. In conclusion, the cGMPu is more stable and easier to measure than the ANF. It would seem to be a sensitive marker of cardiac failure complicating the most common cardiac pathologies observed in clinical practice.     

Circadian variation of left ventricular diastolic function in healthy people

AIM--To assess whether left ventricular function shows circadian variation in healthy people. SUBJECTS AND METHODS--10 healthy men (7) and women (3) aged 35-50 underwent M mode echocardiography of the left ventricle and Doppler velocimetry of transmitral flow at 4 h intervals over 24 h. The participants were in hospital over the study period and their diet, meal times, and sleeping hours were standardised as far as possible. MEASUREMENTS--Heart rate, blood pressure, left ventricular and atrial diameters, fractional shortening, peak early and late transmitral velocities, time from the second heart sound to the early diastolic velocity peak (relaxation time), isovolumic relaxation period, acceleration and deceleration of the early transmitral flow, atrial filling fraction. RESULTS--A circadian rhythm was observed in heart rate and blood pressure, but neither the left ventricular diameters and systolic function nor the left atrial size showed statistically significant diurnal trends. The relaxation time (mean (SD)) measured 144 (16) ms at 2 pm, 144 (21) ms at 6 pm, 149 (22) ms at 10 pm, 168 (23) ms at 2 am, 174 (28) ms at 6 am, and 151 (21) ms at 10 am (P = 0.009). Diurnal rhythms were seen also in the isovolumic relaxation period (P = 0.003) and in the acceleration of the early diastolic transmitral flow (P = 0.037); the lowest and highest values of flow acceleration were observed during the nocturnal and daytime hours, respectively. CONCLUSIONS--The Doppler indices of left ventricular filling in healthy people show diurnal changes suggestive of a circadian rhythm in the rate of left ventricular relaxation. The most likely underlying mechanism is the day-night cycle in sympathoadrenal activity.     

Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women.

To investigate whether bone resorption exhibits a diurnal variation in healthy premenopausal women, we measured urinary excretion of pyridinoline and deoxypyridinoline cross-links (U-Pyr/Cr and U-D-Pyr/Cr) every 3 h over a 24-h period in 12 healthy premenopausal women (mean +/- 1 SD age, 32 +/- 5 yr). To study diurnal variation, U-Pyr/Cr and U-D-Pyr/Cr are the best available markers of bone resorption for a diurnal variation study, as they are not influenced by diet. Plasma osteocalcin and serum alkaline phosphatase (markers of bone formation) were also measured. A marked diurnal rhythm was observed in U-Pyr/Cr and U-D-Pyr/Cr, with the peak between 0500-0800 h and the nadir between 1400-2300 h. The fluctuation was 2-fold over the 24-h period, with a mean fall of 25-35% between 0800-1100 h. This study demonstrates a marked diurnal variation in the new biochemical markers of bone resorption, U-Pyr/Cr and U-D-Pyr/Cr, in premenopausal women. Furthermore, this study emphasizes the importance of regulating the time of the urine sample taken for measuring urinary pyridinium cross-links for clinical investigations as well as in clinical practice.     

健康人尿铜蓝蛋白排泄率随增龄的变化

目的　观察健康人尿铜蓝蛋白排泄率 (CER)随增龄发生的变化 ,并探讨其临床意义。　方法　对 314名 2 0～ 79岁健康者以 10岁为一年龄段分成 6组。采用酶联免疫吸附测定法检测其尿CER。　结果　各年龄组尿CER为 :2 0～ 2 9岁组 (38± 19)ng/min、30～ 39岁组 (42± 2 4 )ng/min、4 0～ 4 9岁组 (45± 2 5 )ng/min、5 0～ 5 9岁组 (48± 32 )ng/min、6 0～ 6 9岁组 (5 3± 33)ng/min、70～ 79岁组 (6 1± 4 3)ng/min ,但各年龄组间差异无显著性 (P >0 0 5 )。非老年组 (47± 30 )ng/min ,老年组(5 9± 39)ng/min ,两组比较差异有显著性 (P <0 0 5 )。　 结论　 (1)增龄过程中尿CER有上升的趋势 ;(2 )尿CER老年组明显高于非老年组 ;(3)对老年患者的临床诊断治疗要考虑因年龄因素而存在的脏器排泄率变化。     

Day-to-day variation and circadian rhythm of egg excretion in urinary schistosomiasis in the Sudan

The daily variation of urinary excretion of Schistosoma haematobium and Schistosoma mansoni ova was assessed in a group of 24 Sudanese schoolboys using the filtration Trypan blue staining technique. An intra-class correlation coefficient of r = 0.88 indicated a surprisingly low daily variation of excretion of S. haematobium ova. All patients with a median egg output of at least 100 ova per 10 ml also voided S. mansoni ova in the urine. The daily variation of S. mansoni ova was slightly greater than for S. haematobium. For an excretion rate of at least five ova per 10 ml, the lower range of mean (P = 0.95) is one, if urine filtration is done on a single day. A circadian rhythm of S. haematobium egg excretion, with a peak around noon, was confirmed. Physical exercise combined with fluid intake prior to micturition significantly increased the egg output at all time points examined.