Follow-up of renal function and urinary protein excretion in childhood IgA nephropathy

Homocystinuria is a rare inherited metabolic disease. Arterial and venous thromboembolic events represent frequent and life-threatening complications in homocystinuric patients. It has been suggested that mild homocysteinemia could be a risk factor for vascular disease. We have therefore measured total plasma homocysteine (HCy) concentrations by radioisotopic assay in 50 subjects with venous or arterial thrombosis and studied the relationship between HCy, coagulation and fibrinolytic parameters. Values were considered abnormal if they were higher than 2.7 standard deviations (SD) above the mean, i.e., 14.1 mmol/l. Thus, eighteen of the 50 patients with thrombosis were classified in the hyperhomocysteinemia group. Nine of these subjects had only this isolated risk factor. No correlations were found between HCy and antithrombin III, protein C, protein S and plasminogen levels, or plasma plasminogen activator inhibitor activity. Nevertheless, the correlation between tissue-plasminogen activator antigen and total plasma HCy was significant (r = 0.61, p < 0.001). Increased homocysteinemia seems to be a risk factor for thrombotic events especially knowing that HCy presents a direct cytotoxic effect. Vitamin therapy, already used in homozygote homocystinuric patients, might be beneficial in the prevention of thromboembolic disease in heterozygous patients.     

Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.     

The importance of urinary protein excretion during conservative management of severe preeclampsia

A chemiluminescence in situ hybridization method was developed for the search of B19 parvovirus DNA in bone marrow cells, employing digoxigenin-labeled B19 DNA probes, immunoenzymatically detected with a highly sensitive 1,2-dioxetane phosphate as chemiluminescent substrate. The light emitted from the in situ-hybridized probe was analyzed and measured by a high-performance luminograph connected to an optical microscope and to a personal computer for the quantification of the photon fluxes from the single cells and for image analysis. The chemiluminescence in situ hybridization was applied to bone marrow cell smears of patients with aplastic crisis or hypoplastic anemia, who had been previously tested by in situ hybridization with colorimetric detection, dot blot hybridization, and nested PCR. The chemiluminescent assay provided an objective estimation of the data, proved specific, and showed an increased sensitivity in detecting B19 DNA compared with in situ hybridization with colorimetric detection.     

Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis

An experimental model of focal sclerosis (FS) following chronic administration of aminonucleoside (AMNS) is described in rats with pathologic features similar to those observed in human steroid-resistant idiopathic nephrotic syndrome. Six groups of rats were given intraperitoneal injections of either 0.9% normal saline or aminonucleoside (13 mg. per 100 gm. of body weight); four groups underwent a right nephrectomy on day 22; a second series of injections of saline or aminonucleoside were then administered to all six groups: group I (five animals), saline-saline; group II (10 animals), AMNS-AMNS; group III (10 animals), AMNS-nephrectomy-AMNS; group IV (five animals), AMNS-nephrectomy-saline; group V (five animals), saline-nephrectomy-AMNS; group VI (five animals), saline-nephrectomy-saline. A relationship between the percentage of glomeruli with focal sclerosis and the total amount of protein excreted during the course of the experiment was observed (r=0.80). An apparent threshold level of protein excretion essential for the development of FS was also noted in that all rats excreting greater than 2.2 integral units developed FS whereas those excreting less than this amount did not. The highest incidence of FS was seen in rats that had received AMNS after unilateral nephrectomy: 62% of glomeruli with FS in group III and 26% in group V; whereas no FS was seen in groups I and VI or in rats evaluated 7 to 23 days after a single injection of AMNS. These studies indicate a quantitative relationship between the breakdown in the permeability barrier to protein and the ultimate development of FS. The prior demonstration of epithelial cell alteration in acute AMNS disease and the morphologic changes presented in this and the subsequent paper (Velosa JA, Glasser RJ, Nevins TE, Michael AF: Lab Invest 36:527, 1977) support the concept that irreversible epithelial cell injury may be the primary event in the development of FS.     

Oestrogen-progestogen oral contraceptives and urinary calcium excretion

To examine the effects of age and use of oestrogen-progestogen oral contraceptive agents (OCA) on urinary calcium excretion, 24 h urine collections were obtained from 525 women aged 16-69 years during a health survey, and measurements made of the amounts of calcium, creatinine, sodium, potassium and magnesium excreted. Younger women using OCA excreted more potassium and creatinine but less calcium, and less calcium and magnesium relative to creatinine, than corresponding controls using no OCA. Older women excreted less creatine, but significantly greater amounts of calcium, sodium, potassium and magnesium relative to creatinine than younger women. It is postulated that the diminished urinary calcium excretion observed in women using OCA resulted from suppression of bone resorption by oestrogens in OCA.     

Effects of phenylbutazone on extravascular diffusion, protein binding and urinary excretion of cefazolin in rabbits

The effects of an anti-inflammatory drug, phenylbutazone, on the disposition of a commonly used cephalosporin, cefazolin, were studied in rabbits. The following investigations were made: mathematical analysis of blood levels obtained after i.v bolous injection of cefazolin, alone or combined with phenylbutazone (10 mg/kg), injection 4 hr before; protein binding by ultracentrifugation in vitro; and renal excretion and distribution in extravascular fluid obtained from s.c. tissue cages in vivo. Single i.m. injections of cefazolin (30 mg/kg) were administered either alone or in combination with phenylbutazone (10 or 100 mg/kg i.m.) or 2 or 4 hr before. The mathematical analysis disclosed a competition of phenylbutazone on protein binding of cefazolin. In vitro, phenylbutazone reduced the extent of protein binding of the antibiotic (74-80 to 47-59%). Cefazolin appeared at higher concentrations in extravascular fluid in the presence of phenylbutazone than when administered alone. Phenylbutazone appeared to be responsible for a dose-dependent effect on renal excretion of cefazolin i.e., a reduction of secretion at low doses (10 mg/kg) and a possible reduction of tubular reabsorption at high doses (100 mg/kg). A bidirectional transport of cefazolin in rabbit tubules was thus shown. The interaction of phenylbutazone on the on the disposition of cefazolin appeared also dependent on the time of injection of the former and on the mode of administration of the antibiotic.     

Low urinary dopamine excretion associated to low sodium excretion in normotensive Piaroa Amazonian ethnia compared to urban subjects

The objective of this work was to compare urinary dopamine, noradrenaline, adrenaline, sodium and potassium excretion in a group of normotensive Piaroa Amazonic ethnia who do not use salt in their regular food intake, against a group of urban normotensive citizens known to have a high salt intake in their regular meals. Twenty adult normotensive Piaroa subjects living in the Amazonas forest, 11 men and 9 women, 23-72 years old, and 33 normotensive urban citizens, 25-70 years old, 17 men and 17 women, were included in the study. After a 10 min. rest, an average of three supine systolic (SBP) and diastolic (DBP) blood pressure recordings was obtained. Piaroas subjects SBP and DBP were 111.3 +/- 2.9 mmHg and 62.7 +/- 1.9 mmHg respectively; urban subjects SBP and DBP were 111.8 +/- 2.2 mmHg and 70.3 +/- 1.6 mmHg respectively. Supine heart rate was lower in Piaroas (58.0 +/- 1.8 beats/min) than in urban subjects (76.5 +/- 1.9 beats/min), p < 0.05. Sodium urinary excretion was much lower in Piaroas (12.6 +/- 5.2 mmol/24 h) when compared to urban subjects (210.7 +/- 24.5 mmol/24 h), p < 0.01. No difference was found in daily urinary potassium excretion between Piaroas and urban subjects (50.4 +/- 7.2 mmol/24 h vs 45.1 +/- 7.4 mmol/24 h). Urinary dopamine excretion was lower in Piaroas (314.7 +/- 40.1 micrograms/24 h) in comparison to urban subjects (800.4 +/- 59.2 micrograms/24 h), p < 0.05. Daily urinary noradrenaline and adrenaline excretion were 67.9% and 85.4% respectively lower in Piaroas than in urban subjects. In conclusion, lower amounts of sodium daily intake are associated to lower kidney dopamine production in Piaroas as compared to urban subjects. Apparently indigenous tribes might require less kidney dopamine synthesis to excrete the very small amounts of salt they consume in their regular food intake. The opposite was found in urban subjects; more kidney dopamine synthesis would be required for larger amounts of urinary sodium excretion. In this population, essential hypertension has been associated to a failure of the natriuretic mechanism triggered by dopamine onkidney tubules.     

Dietary protein intake and urinary excretion of calcium: a cross-sectional study in a healthy Japanese population

Efforts in dental research and training have received the contribution of individuals who had no formal training in dentistry, yet they understood the dental field and the educational needs of those who would be engaged in dental research, teaching, and service in industry and academia. Dr. Robert S. Harris (1904-1983) was such a man. What follows is a personal remembrance of his character, his research accomplishments, and his successful educational endeavors in the dental field.     

Circadian variations of the urinary excretion of catecholamines and electrolytes

Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.     

Dietary influence on the urinary excretion of polyamines

The amino groups of amino acids, the constituents of proteins, are catabolized in the urea cycle. One intermediate of this cycle, ornithine, is a precursor molecule of polyamines. The influence of dietary protein intake on the production and excretion of polyamines in the urine is yet unclear. The aim of this study was to investigate the excretion of polyamines in the urine following three days of creatine-free, creatine-free and low-polyamine diet in four persons. On the fourth day they were loaded with creatine-free, creatinine-free and low-polyamine high-protein diet (80 g/70 kg body weight). High-protein diet resulted in no increase of urinary polyamine excretion. The low-polyamine diet caused a non-significant decrease in urinary polyamine excretion (by 15%).     

Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks

This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia.     

In vitro dissolution and urinary excretion study of metoclopramide tablets

Changes in cardiac troponin I (cTnI) in Kawasaki disease before and after treatment with intravenous gamma-globulins (i.v.GG) were investigated in 42 cases in order to confirm the usefulness of cTnI as a serological test for the early onset of acute myocarditis and the effectiveness of i.v.GG as treatment for it. The level of cTnI before i.v.GG treatment was increased in 42.9% (18/42), but 89% (16/18) were in the normal range after treatment as shown by improved clinical symptoms and signs; 9.5% (4/42) were treated twice with i.v.GG because of recurrent high fever, with a positive level of cTnI in the second test. Despite the improved clinical symptoms and signs after retreatment with i.v.GG, 4.7% (2/42) continued to have an increased level of cTnI in follow-up studies. In conclusion, the measurement of cTnI is a useful serologic test for the early diagnosis of myocarditis or myocardial cell injury and for confirming the effectiveness of i.v.GG therapy for the cure and prevention of cardiovascular abnormalities in KD patients.     

Relationship between serum 1,5-anhydroglucitol and urinary excretion of N-acetylglucosaminidase and albumin determined at onset of NIDDM with 3-year follow-up

A nonsense codon suppression technique was employed to incorporate ortho-nitrobenzyl tyrosine, "caged tyrosine," in place of tyrosine at any of three positions (93, 127, or 198) in the alpha subunit of the muscle nicotinic ACh receptor (nAChR) expressed in Xenopus oocytes. The ortho-nitrobenzyl group was then removed by 1 ms flashes at 300-350 nm to yield tyrosine itself while macroscopic currents were recorded during steady ACh exposure. Responses to multiple flashes showed (1) that each flash decages up to 17% of the tyrosines and (2) that two tyrosines must be decaged per receptor for a response. The conductance relaxations showed multiple kinetic components; rate constants (<0.1 s(-1) to 10(3) s(-1)) depended on pH and the site of incorporation, and relative amplitudes depended on the number of prior flashes. This method, which is potentially quite general, (1) provides a time-resolved assay for the behavior of a protein when a mutant sidechain is abruptly changed to the wild-type residue and (2) will also allow for selective decaging of sidechains that are candidates for covalent modification (such as phosphorylation) in specific proteins in intact cells.     

Measurement of urinary iodine excretion to reveal iodine excess in neonatal transient hypothyroidism

This study was undertaken to confirm the importance of iodine excess in neonatal transient hypothyroidism. In 30 transient hypothyroid newborns at screening we measured urinary iodine excretion and TSH. They were divided into two groups: group A consisted of 21 newborns who had been exposed to iodine; group B of 9 non-exposed newborns. The two groups were significantly different only for median urinary iodine excretion (p = 0.001). In 61.5% of newborns of group A, iodine exposure caused iodine excess (urinary iodine excretion higher than 185 micrograms/l); this correlated with a higher prevalence of prematurity and a lower mean gestational age. Clinical records should reveal iodine exposure, but only urinary iodine excretion shows iodine excess. We suggest that evaluation at birth of urinary iodine excretion in every newborn with high TSH could help in predicting a good prognosis, since hypothyroidism due to the Wolff-Chaikoff effect is always spontaneously reversible, even if treatment may be suggested.     

Tissue distribution and urinary excretion of essential elements in rats orally exposed to aluminum chloride

The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl3. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.     

Relationship of age, age at onset, and sex to depression in older adults

The authors investigated the relationships among factors of age, age at onset, and sex in depressed older adults. A group of 96 outpatients (mean age, 60) diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed for severity of depression and underwent magnetic resonance imaging (MRI). The MRI scans were rated for severity of white-matter hyperintensities (WMH) and ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH, larger VBR, and history of hypertension. Men were more severely depressed than women, with higher rates of neurovegetative signs and history of smoking. Age correlated with increased VBR and WMH, history of hypertension, history of percipitants for the current episode, and lack of social support. Results suggest that a subgroup of men may be more at risk for LOD associated with WMH and that sex and age at onset need to be considered in future studies.     

Increased urinary thyroxine sulfate excretion in thyroxine therapy

The efficiency of hemato-C-cellular transport of calcitonin into the systemic blood flow was evaluated by the methods of statistical modelling. The linear regression model obtained on 36 rats suggests essential predetermination of the serum concentrations of calcitonin (CT) by the intensity of incretory activity of the thyroid parafollicular epithelium: CT = 13.733+ (0.318 Nvsg; rxy = 0.830; p < 0.001 (Nvsg is numerical density of the sublemmal granules on the C-cells vascular pole). At the same time, the resulting index (CT) depends not only on Nvsg. This index is also influenced by the factors not controlled by the model, such as Hemato-C-cellular delay of calcitonin. These factors determine each certain proportion of the error of prognostication of the calcitonin serum content according to Nvsg. A covariation model CT = bNvsg was plotted in order to determine the total influence of uncontrolled factors. Its error of prognostication was subject to analysis of variance and a confidence interval of biological accessibility of endogenous calcitonin was calculated (73% < FCT < or = 100%; p > or = 0.95). The results obtained suggest the absence of essential intrathyroid loss of calcitonin at the transinterstitial and transmural stages of hemato-C-cellular hormone transfer.     

Reduction of urinary mutagen excretion in rats fed garlic

Naturally occurring substances of plant origin are known to possess antimutagenic potential. Garlic (Allium sativum) was fed to rats in dried powdered form at 0.1%, 0.5% and 1% concentrations in their diet for 4 weeks. At the end of the experiment benzo[a]pyrene (1 mg/rat) was injected intraperitoneally and 24-h urine was collected from the rats. Urinary mutagens were quantitated by the Salmonella typhimurium assay. There was a significant reduction in the excretion of urinary mutagens by carcinogen-exposed rats fed garlic. Further, there was a stimulation in the activities of liver cytosolic glutathione-S-transferase and liver and lung quinone reductases. The study suggested that the antimutagenic potential of garlic may be mediated through induction of detoxification enzymes in target tissues.