Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.

Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.     

Androgen imbalance in premenopausal women with benign breast disease and breast cancer.

OBJECTIVE: The alteration of steroid hormonal status in premenopausal breast disease (benign and malignant) were investigated by comparing the urinary profile of androgens and corticoids. METHODS: The urinary concentrations of 25 androgens and corticoids were quantitatively determined by a gas chromatographymass spectrometry system in patients with benign breast disease (35 cases, 20-54 years), breast cancer (34, 27-54), and healthy controls of similar age (25, 22-51). RESULTS: In premenopausal patients with breast cancer, a significantly lower rate of excretion of 11-deoxy-17-ketosteroids and their metabolites was found in comparison with normal females. These levels were also inversely associated with benign breast disease. No significant differences were found between the three groups for the concentration of 11-oxy-17-ketosteroids, 17-hydroxy-corticoids and their metabolites. The urinary ratio of adrenal androgen metabolites to cortisol metabolites [(11-DOKS & M)/11-OKS] declined in the order of normal female control (4.04 +/- 0.72; mean +/- SD), breast benign mass (2.29 +/- 0.42) and breast cancer (0.94 +/- 0.27). CONCLUSION: Our data suggest that the hormonal imbalance of androgen deficiency and/or corticoid sufficiency is closely associated with the benign and malignant conditions of premenopausal breast disease and the ratio of (11-DOKS & M)/11-OKS may be an effective discriminant factor of these groups.     

Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients.

The effects of a 48-hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady-state plasma level of 1798 +/- 481 ng/ml. Biphasic, rapid elimination of pirmagrel was observed with a distribution half-life of 6.7 minutes and a terminal half-life of 73 minutes. Plasma clearance and the volume of distribution of the drug were 300 +/- 87 ml/hr/kg and 497 +/- 232 ml/kg, respectively. The pharmacodynamic effects of pirmagrel were marked by a mean 96% suppression of serum thromboxane B2 (TXB2), which coincided with a suppression of urinary excretion of TXB2, 2,3-dinor-TXB2, and 11-dehydro-TXB2 of 85% +/- 8%, 91% +/- 5%, and 89% +/- 9%, respectively. Urinary excretion of all thromboxane metabolites measured at the end of 1 week after termination of infusion was returned to the baseline. In conclusion, pirmagrel caused effective and sustained suppression of all thromboxane derived metabolites in plasma and urine during continuous infusion in kidney transplant patients receiving cyclosporine.     

Plasma and Urinary Dopamine: Studies During Fasting and Exercise and in Tetraplegic Man

Dopamine, noradrenaline and adrenaline were measured in plasma and in urine, using double-isotope derivative techniques, in 46 normal subjects and in 17 tetraplegic patients with physiologically complete cervical spinal cord transections above the sympathetic outflow. Dopamine was present in plasma in normal subjects in a concentration of 0.33 μg/1 ± 0.06 (SEM). Twenty-four hour urinary excretion of dopamine averaged 248 yg ± 22. There was a significant correlation between the 24 h urinary excretion of dopamine and of noradrenaline. In the normal subjects plasma dopamine and the urinary excretion of dopamine did not change during three days of fasting while urinary excretion of adrenaline increased twofold. In the normal subjects exercise significantly increased plasma dopamine from 0.25 μg/1 to 0.43 μg/1, but significantly decreased the urinary excretion of dopamine. Exercise significantly increased the excretion of noradrenaline. In the tetraplegic patients the plasma dopamine concentration and the urinary excretion of dopamine were lower but not significantly different from the corresponding values in the normal subjects. Plasma noradrenaline and the urinary excretion of noradrenaline and adrenaline were significantly lower in the tetraplegic patients. It is concluded that dopamine is present in human plasma in concentrations similar to that of noradrenaline. Free dopamine in plasma and urine of normal subjects is not dependent on food intake. Urinary dopamine may be derived from circulating dopamine. Urinary dopamine does not necessarily appear to reflect changes in plasma dopamine. The relationship between plasma dopamine and changes in adrenergic nervous activity deserves further investigation.     

Analysis and HPLC fractionation of urine from patients with cystic fibrosis, chronic lung diseases and normal controls

The amounts of creatinine, protein, carbohydrate and sialic acid in the urine of 19 patients with cystic fibrosis (CF), 12 normal controls and 11 pathological controls with chronic lung disease have been determined. The mean creatinine excretion levels of the total CF group as well as the CF subgroups are significantly decreased when compared to normal controls but comparable to pathological controls. Mean urinary protein levels appear to be increased in patients with CF compared to normal controls and pathological controls but the increased levels resulted from factors (e.g., presence of diabetes mellitus) other than CF. No significant differences were found in amounts of total carbohydrate and sialic acid in urine and fractionated urinary preparations for the total group of nondiabetic patients with CF when compared to both normal and pathological controls. HPLC fractionation of low Mr (less than 10,000 Daltons) urinary preparations indicated the presence of an unknown peak in all of the antibiotic-treated CF patients, 43% of CF patients on low or no medication, 17% of the normal controls and 9% of the pathological controls. The present results illustrate the importance of including appropriate pathological controls and dividing patients with CF into subgroups according to clinical factors and types of therapy employed.     

The identification of urinary bile alcohols by gas chromatography–mass spectrometry in patients with liver disease and in healthy individuals

Abstract. The neutral steroid fractions in the urine of eleven patients suffering from various forms of liver disease with cholestasis and of ten healthy individuals were studied by glass capillary gas chromatography-mass spectrometry. The steroid conjugates in urine were enzymatically solvolysed, the liberated steroids extracted and transformed into the trimethylsilylether for measurements.
The excretion rates of androstane and pregnane metabolites of patients with liver disease were far lower than those of healthy persons. The main compounds in the urine of the former were the bile alcohols 27 - nor -3α, 7α, 12α, 24, 25 - pentahydroxy - 5β - cholestane and 3α, 7α, 12α, 25, 26 - pentahydroxy - 5β - cholestane. Our data suggest a correlation between the excretion rates of these bile alcohols and the serum levels of bilirubin. While the excretion rate of the two bile alcohols in the urine of healthy individuals was approximately 0.24 mg/24 h (0.6 μmol/24 h) a patient with a serum bilirubin of 841 μmol/1 excreted 4 mg/24 h (9 μmol/24 h). The accumulation of bile alcohols described in this study possibly indicates alternative pathways of cholic acid formation in liver disease.     

beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome

BACKGROUND: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of gamma-aminobutyric acid (GABA) and/or its structural analogue beta-alanine in the urine from CFS patients. Both GABA and beta-alanine are inhibitory neurotransmitters in the mammalian central nervous system. METHODS: The 24 h urine excretion of GABA and beta-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale. RESULTS: Men had a significantly higher excretion of both beta-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither beta-alanine nor GABA. No correlation was found between the excretion of beta-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of beta-alanine in their 24 h urine samples than control subjects. CONCLUSIONS: Increased excretion of beta-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and beta-alanine in some CFS patients.     

Atrial natriuretic factor, cyclic 3'',5''-guanosine monophosphate and prostaglandin E2 in liver cirrhosis: relation to blood volume and changes in blood volume after furosemide

Plasma concentrations of atrial natriuretic factor (ANF) and cyclic 3',5'-guanosine monophosphate (cGMP) were measured in 11 cirrhotic patients with ascites, 11 cirrhotic patients without ascites and 15 control subjects. The following were determined in 15 of the cirrhotic patients and in all the control subjects: blood volume (BV) and furosemide-induced changes in BV, plasma values of ANF, cGMP, angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion rates of cGMP, prostaglandin E2 (PGE2), water and sodium. Basal plasma levels of ANF and cGMP were higher in patients with cirrhosis than in controls, but were the same in both groups of cirrhotics (ANF: cirrhosis with ascites 12.7, without ascites 13.4, and in controls 5.8 pmol l-1 (medians); cGMP: 7.7, 7.4 and 4.3 nmol l-1, respectively). BV was less reduced after furosemide in the cirrhotic patients (6.0%) than in the healthy subjects (10.1%), but basal BV did not differ. Urinary sodium excretion rates after furosemide were significantly lower in the cirrhotic patients than in the controls. PGE2 excretion rate increased after furosemide in the cirrhotic patients (0.29 to 0.66 pmol min-1; P less than 0.01) but not in the controls (0.31 to 0.38 pmol min-1). After furosemide ANF and cGMP decreased slightly in both groups whereas AII and Aldo increased; AVP increased in the controls, but not in the cirrhotic patients. In conclusion, plasma values of ANF and cGMP are increased in liver cirrhosis both with and without ascites. This and the elevated PGE2 excretion after furosemide may be compensatory phenomena in order to facilitate renal sodium excretion.     

Increased urinary excretion of prostaglandin E in patients with idiopathic hypercalciuria

1. Because urinary prostaglandin excretion could play a role in idiopathic hypercalciuria (IH), we studied the excretion of prostaglandin E (PGE), calcium and sodium at various urine flows in 21 patients (14 males) with urolithiasis and IH, seven stone formers (five males) with normal calciuria and 20 controls (11 males). Dietary composition was comparable and sodium intake was restricted to 100-120 mmol/day. 2. Analyses were performed on 30 min urine collections obtained after overnight water deprivation and during water diuresis. Male IH patients had increased levels of urinary PGE at all ranges of urine flow. PGE excretion correlated directly with urine flow in patients and controls, but the slope of this relationship in individual IH male patients was steeper than in controls (P less than 0.01). Calciuria correlated directly with urine output in patients with IH but not in controls. Calcium and sodium excretion were directly correlated (P less than 0.0001) in patients and controls. There were no significant differences between absorptive IH (seven patients) and renal IH (eight patients). There were no significant differences between stone formers with normocalciuria and control subjects. 3. The findings suggest that increased urinary PGE could play a role in the hypercalciuria syndrome, possibly by promoting natriuresis.     

Influence of the parasympathetic and sympathetic nervous system on nocturnal bronchial obstruction

To determine whether an autonomic nervous system imbalance might underlie the nocturnal dyspnoea in patients with chronic airflow obstruction (CAO), we determined FEV1, sinus arrhythmia gap (SA gap), heart rate and urinary adrenaline and noradrenaline excretion every 4 h over 24 h. Measurements were performed in eight non-allergic patients with CAO and eight age- and sex-matched normal controls. The amplitude of the circadian changes in FEV1 in patients and controls was 27 +/- 2% and 7 +/- 1% respectively (P less than 0.001). Both an increased SA gap and a decreased heart rate are features of increased vagal activity. This vagal activity was significantly increased in patients, compared with normal controls (difference P less than 0.01), the difference being maximal at night. This increased activity might contribute to a bronchial obstruction in these patients. Urinary adrenaline excretion was significantly higher by day than by night in both patients and normal controls (P less than 0.01). The urinary levels of adrenaline in the patients were significantly decreased at all hours of observation as compared with levels in normal controls (P less than 0.05). Urinary noradrenaline levels were significantly lower in patients as compared with normal subjects (P less than 0.01), and lower by night than by day. Urinary histamine and Nt-methylhistamine excretion were in the normal range in each individual. Urinary levels, however, were significantly higher in patients at all hours of observation (P less than 0.05). No circadian rhythm was shown. Plasma cortisol levels showed a normal circadian variation, similar in patients and normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation

Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.     

Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine

Abstract. The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2–3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso-ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1β, 12β, 6α- and 21,22-hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 ± 1.1 to 18.4 ± 9.5 μmol l^-1 (mean ± SD, P < 0.005) and from 5.6 ± 1.3 to 13.1 ± 7.9 μmol g^-1creatinine (mean ± SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid. Ursodeoxycholic acid became the major bile acid in serum and urine contributing 46% and 50% to total bile acids. 14% ursodeoxycholic acid in serum were in the unconjugated form, 42% in the amidated form and 45% in the sulfated form; the percentages in urine were 11%, 23% and 66%. Iso-ursodeoxycholic acid was higher in serum and urine than in bile and contributed 16% and 8% to total bile acids. Iso-ursodeoxycholic acid was present in serum and urine only as the unconjugated and sulfated species. Other iso-bile acids and 3β-hydroxy-5-cholenoic acid were found in bile only in traces, but contributed 8% to total bile acids in serum and 10% in urine. In serum and urine the sulfated form of lithocholic acid prevailed and was significantly enhanced after ursodeoxycholic acid ingestion. Further metabolites of ursodeoxycholic acid in urine were tentatively identified to be hydroxylated at postitions 1β, 5α, 6α and 22 and contributed about 10–15% of urinary UDCA.     

Circadian Variations in Urine Excretion in Chronic Renal Failure

The pattern of urine excretion over 24 hours has been studiedin nineteen patients with stable chronic renal failure of varyingseverity and due to a variety of renal disorders. The patternswere compared with those in eighteen healthy control subjectsof similar age. The 24 hour urine volume was not significantlygreater in the patients (1608 ml ± 112 compared with1710 ml ± 169). A lower urine concentration (341 ±79 mOsm compared with 430 ± 160 mOsm/kg) was associatedwith a lower total 24 hour solute excretion (596 ± 224compared with 699 ± 169 mOsm/24 hours). Frequency ofmicturition, expressed in relation to periods of 24 hours, wassimilar (6.8 ± 0.6 compared with (6.4 ± 0.5).There was an alteration in the normal pattern of urine flow,with more urine at night and less in the day. Nocturia, a consistentfeature of the patients with renal failure is due to reversalof the normal pattern and not to an increased volume of urineor increased frequency of micturition. The time of onset of decreased urine excretion during the daywas associated with the change from recumbency to activity.The morning antidiuresis, and the nocturnal diuresis, are associatedwith, and probably the result of, changes in sodium and totalsolute excretion. The circadian rhythm of potassium excretionremained normal in chronic renal failure, except in very severerenal failure when it was reversed. Alterations in sodium, totalsolute and water excretion were associated with changes in creatinineexcretion and were observed even in mild renal failure. In some patients, studied just before commencing regular dialysis,renal function would have been adequate for reasonable healthhad the rates of excretion observed at night persisted throughoutthe 24 hours. Nocturia, in nineteen patients with chronic renal failure, wasdue to a change in the circadian pattern of urine flow; it issuggested that this results, at least in part, from an inabilityto respond normally to changes from recumbency to activity.     

实时三维超声心动图及组织多普勒评价心脏移植术后右心室功能的变化

目的探讨超声心动图参数在诊断心脏移植术后排斥反应中的价值。方法2000年8月至2008年12月在复旦大学附属中山医院行心脏移植后随访的患者30例,根据心内膜活检（EMB）和临床诊断分为排斥组（A组）和非排斥组（B组）。选取健康体检成年人30例作为正常对照（C组）。所有研究对象行常规超声心动图检查;脉冲多普勒记录三尖瓣、肺动脉瓣血流图;组织多普勒记录三尖瓣环右室侧壁频谱;实时三维超声心动图（RT3DE）采集右室全容积图像储存光盘并进行脱机分析。结果（1）A、B组左房内径均大于C组（P均〈0．05）。A组右室射血分数明显低于B组（P〈0．01）,B组右室射血分数略低于C组（P〈0．05）。（2）A、B组右室每搏输出量小于C组（P均〈0．05）,A组右室体部和流出道部局部射血分数均小于B组和C组（P均〈0．05）,B组右室流出道部射血分数小于C组。（3）A组三尖瓣环右室侧壁的收缩速度较B组降低（P〈0．05）,B组右室侧壁的收缩速度和A峰峰值速度低于C组（P〈0．05）。（4）RT3DE测得的右室射血分数与右室Tel指数及三尖瓣环右室侧壁的收缩速度有较好相关性（r分别为0．592和0．543,P〈0．01）。结论心脏移植术后排斥患者右室收缩功能较正常人明显下降,非排斥患者右室收缩功能较正常人略有下降,实时三维右室射血分数和组织多普勒参数有助于心脏移植术后排斥反应的诊断。     

Stereodifferentiation of 3-hydroxyisobutyric- and 3-aminoisobutyric acid in human urine by enantioselective multidimensional capillary gas chromatography-mass spectrometry

The chiral metabolites 3-hydroxyisobutyric acid (HIBA) and 3-aminoisobutyric acid (AIBA) are intermediates in the pathways of L-valine and thymine and play an important role in the diagnosis of the very rare inherited metabolic diseases 3-hydroxyisobutyric aciduria (McKusick 236975) and methylmalonic semialdehyde dehydrogenase deficiency (McKusick 603178-MSDD). Until now only a few approaches have been made in enantioselective analysis of HIBA and AIBA and for that reason very little information is available on enantiomeric ratios of these metabolites in man. This paper reports on the simultaneous stereodifferentiation of HIBA and AIBA in human urine as corresponding N(O)-methoxycarbonyl methyl esters by derivatization with methyl chloroformate (MCF) using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC/MS) with heptakis-(2, 3-di-O-methyl-6-O-tert.-butyl-dimethylsilyl)-beta-cyclodextrin as the chiral stationary phase. During this investigation urine samples from different patients and healthy controls were analyzed in order to reveal characteristic enantiomeric patterns of these metabolites. A trend of dominating R-HIBA excretion in the control urine samples investigated was observed. An excretion of more than 80% S-HIBA was found in the urines of two patients with ketonemic vomiting. There are some clues indicating a possible renal reabsorbtion of S-HIBA similar to those of S-AIBA. Furthermore, there was a significant finding with regard to the enantiomeric distribution of AIBA in a patient with MSDD - a markedly increased excretion of the S-enantiomer in contrast to the other samples. Using the enantiomeric ratios of AIBA, a previously investigated case of benign methylmalonic aciduria (bMMA) could be excluded from the diagnosis of MSDD.     

Corticosteroid production in abetalipoproteinemia: evidence for an impaired response ACTH

The concept that an inherent absence of plasma LDLs may be associated with a reduced synthesis of steroid hormones has been evaluated in two patients with ABL. Basal production of adrenal corticosteroids, assessed by the concentrations of serum cortisol and the rates of excretion of urinary 17OHCS and 17KS and urine free cortisol, was normal in both patients with ABL. Prolonged stimulation (24 to 36 hr) with ACTH, however, disclosed an impairment in adrenal corticosteroid production in both patients with ABL (as compared to normolipidemic controls), which was manifest by lower serum cortisol levels, reduced rates of urinary excretion of 17OHCS and 17KS and a marked decrease in the excretion of urine free cortisol. These results provide in vivo evidence to support the view that plasma LDLs serve as an important source of cholesterol for adrenal corticosteroid synthesis during prolonged stimulation with ACTH but show that a total absence of LDL does not impair adrenal steroidogenesis in the basal state.     

Alterations of glomerular and extracellular levels of glutathione peroxidase in patients and experimental rats with diabetic nephropathy

To investigate the status and role of glutathione peroxidase (GPX) in diabetic nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these patients and in rats with streptozotocin-induced diabetes of varying duration. Plasma GPX levels were significantly lower in DGS patients than in diabetic patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX concentrations were also significantly lower in DGS patients than in diabetic patients without nephropathy or normal controls (both P < .05). Immunostaining of glomerular GPX was significantly less in DGS patients than in normal controls (P < .05) and was negatively correlated with the glomerular sclerosis score and the index of mesangial expansion. Serial examination of glomerular GPX in diabetic rats showed that immunostaining scores for glomerular GPX in rats were significantly lower than those in normal control rats after 1 and 3 months' duration of diabetes, and staining scores were also significantly lower in rats killed after 3 months of diabetes than in those killed after 1 week. In conclusion, our study demonstrates that GPX concentrations in plasma, urine, and glomeruli are decreased in individuals with DGS and that the immunostaining of glomerular GPX decreases progressively.     

Relationship between urinary prostaglandin E2 and F2α excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients

Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.     

Evaluation of aminoaciduria in severely traumatized patients.

BACKGROUND: It has been documented in the literature that hypocalcemia, hypoaminoacidemia, and hyperaminoaciduria are sequelae of trauma. The aminoaciduria of patients with different types and severity of traumatic injuries was investigated. METHODS: Eight severely traumatized patients (ISS range, 20-43 years) and eight age-, gender-, and weight-matched controls were studied. Plasma and urine were collected 2.5-72 h after admission. Quantification of 28 amino acids in plasma and urine was performed by reversed-phase high-performance liquid chromatography. Urine concentrations of amino acids were indexed to creatinine. RESULTS: The patients' mean serum concentrations of 4 amino acids (arginine, threonine, isoleucine, and glutamine) were significantly decreased, 2 others (tryptophan and glutamic acid) were significantly increased, and 22 were unchanged (p-value< or =0.05). Fractional (urinary) excretion of 11 amino acids was increased in the patients. The patients' serum total calcium and albumin concentrations were decreased, but the mean ionized calcium concentration was not significantly different from the controls. CONCLUSIONS: The results of this study showed that aminoaciduria involving many amino acids is common for patients with different traumatic injuries and that the aminoaciduria is correlated with a reduction of the total serum calcium concentration.     

Elevation of two molecular forms of adrenomedullin in plasma and urine in patients with acute myocardial infarction treated with early coronary angioplasty

Adrenomedullin (AM) has vasodilatory, diuretic and natriuretic actions. Two molecular forms of AM circulate in human plasma: an active, mature form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly). In the present study we investigated the pathophysiological significance of the two molecular forms of AM in plasma and urine in patients with acute myocardial infarction. We serially measured venous and arterial plasma levels and urinary excretion of AM-m, AM-Gly and total AM (Am-T; =AM-m+AM-Gly) over 2 weeks using our recently developed immunoradiometric assay in 26 consecutive patients with acute myocardial infarction and in age-matched normal controls, and studied the relationships between AM levels and clinical parameters. Plasma AM-m, AM-Gly and AM-T levels were increased on admission in patients with acute myocardial infarction compared with age-matched normal controls. Levels of AM-m, AM-Gly and AM-T in plasma reached a peak 24 h after the onset of symptoms. Plasma AM-m, AM-Gly and AM-T levels were significantly correlated with plasma levels of brain natriuretic peptide and pulmonary arterial pressure. Plasma AM-Gly levels in the vein were similar to those in the artery, whereas plasma AM-m levels were significantly lower in the artery than in the vein. Urinary excretion of AM-m, AM-Gly and AM-T was also increased on admission, and reached a peak at 12 h after the onset of symptoms. Urinary excretion of AM-m and AM-Gly was significantly correlated with urinary sodium excretion. The AM-m/AM-T ratio was significantly higher in the urine than in the vein or artery. AM-m levels were significantly correlated with AM-Gly levels in both the urine and plasma; however, there were no significant correlations between plasma and urinary AM levels. The results suggest that levels of both molecular forms of AM are increased in the urine as well as in the plasma in the acute phase of myocardial infarction. Since AM exerts potent cardiovascular and renal effects, increased concentrations of AM in plasma and urine in the acute phase of myocardial infarction may be involved in the defence mechanism against further elevations of peripheral and pulmonary vascular resistance and oliguria in acute myocardial infarction.