Albumin excretion with urine in a population of healthy individuals

Increased urine albumin excretion is the significant prognostic factor for diabetes, hypertension and coronary artery disease. Divergences of the evaluation of albuminuria in different ethnic groups were found. The aim of our study was to evaluate albumin excretion in large group of healthy individuals. 301 healthy subjects (110 female and 191 male), age 20-60 years (mean 32.9 +/- 9.7), were admitted. A questionnaire including data concerning familial history, smoking habits was fulfilled. Subsequently nighttime urine sample was collected in all examined subjects and albumin to creatinine ratio (A/K) was counted. A/K value varied between 0.03-14.1 mg/mmol of creatinine median 1.18. Significantly higher albuminuria in female v male group was found (respectively 1.39; 0.14-14.1 and 1.03; 0.03-11.4 p < 0.05). Reference value for albuminuria was estimated at 3.35 mg/mmol in whole group, and respectively 4 mg/mmol in female and 2.6 mg/mmol in male. There were not differences in A/K ratio in relation to familial history however smoking men excreted more albumin v non smoking (respectively 1.27, 0.03-11.4 and 0.95, 0.14-14.1 mg/mmol p < 0.005). Performed analysis allowed to calculate the value for albuminuria in healthy subjects. Analysis also showed significant influence of gender and smoking habits and no influence of familial history for albumin excretion.     

Negligible excretion of unchanged ketoprofen, naproxen, and probenecid in urine

On the average, 0.6% of a dose of ketoprofen or naproxen or 1.2% of a dose of probenecid was found in the urine of normal male volunteers assayed immediately after its collection. Between approximately 60 and 85% of the dose of these drugs can be excreted in the urine as conjugates, which rapidly hydrolyze at body temperature, at room temperature, and even during frozen storage, thereby regenerating the parent drug. Since urine collections involved sample retention in the bladder at 37 degrees for collection intervals as long as 2--3 hr, the given percentages excreted unchanged probably are overestimates. It is possible that no unchanged ketoprofen, naproxen, or probenecid is excreted in urine. This study contrasts with previous reports of up to 50% of a dose of ketoprofen and 15--17% of doses of naproxen and probenecid being excreted in urine as the parent compound. Those reports probably reflect primarily the duration of frozen sample storage between collection and assay along with the urine collection schedules employed the speed of the clinical procedures, and the analytical procedures used. Attention should be given to potential conjugate hydrolysis whenever the pharmacokinetics of carboxylic acids are studied.     

Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration

Increased monoamine metabolism in experimental herpes simplex virus (HSV) encephalitis is well established. Both serotonin (5-HT) and dopamine (DA) systems are affected. HSV invades the raphe nuclei after its entry into the brain stem. However, no studies have been published concerning influences of HSV on the neurotransmitters in the raphe. In the present study, concentrations of 5-HT and DA and their metabolites in the raphe nuclei and related brain regions in rabbits with fulminant HSV encephalitis have been analyzed using high-pressure liquid chromatography. Encephalitis was induced by corneal inoculation with HSV. Homovanillic acid (HVA) and dihydroxyphenyl acetic acid (DOPAC) concentrations and HVA/DA ratios were increased in the raphe nuclei suggesting increased DA turnover. The most substantial changes were bilaterally decreased 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the raphe nuclei. The decrease in the raphe 5-HT was reflected also to the projection areas in the hemispheres, where 5-HT concentrations were lower in HSV-inoculated rabbits than in controls. The changes strongly suggest a direct influence of HSV on serotoninergic neurons. Since the ventral parts of the limbic system have rich serotoninergic afferents from the raphe, this also suggests that HSV may reach hemispheres in HSV encephalitis from the brain stem via the ascending serotoninergic system.     

Radioimmunoassay for a novel lignan-related hypocholesterolemic agent, S-8921, in human plasma after high-performance liquid chromatography purification and in human urine after immunoaffinity extraction

The novel compound methyl-1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8- trimethoxy-2-naphthoate (S-8921) has hypocholesterolemic activity in animals and is expected to exhibit a similar activity in human. Reversed-phase high-performance liquid chromatography (HPLC) separation followed by radioimmunoassay (RIA) for human plasma samples (HPLC-RIA) and immunoaffinity extraction (IAE) followed by RIA for human urine samples (IAE-RIA) were developed for investigation of S-8921 behavior in clinical studies. For the RIA, antisera from rabbit and a radioiodine-labelled S-8921 were prepared by immunizing a conjugate of S-8921 with bovine serum albumin and by the Bolton and Hunter method, respectively. HPLC-RIA using a semi-micro column was very sensitive, that is a 0.05 ng/ml limit of quantitation in human plasma, and specific for unchanged form of S-8921. IAE-RIA using a centrifugal filtration tube completely eliminated the matrix effect of human urine, and was very feasible. The limit of quantitation was 0.10 ng/ml. RIA detection following HPLC or IAE proved to be very useful for the pharmaceutical analysis of extremely low drug concentrations in body fluids.     

Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria

Suberylglycine (HOOC(CH2)6CONHCH2COOH) was found in the urine from a patient with C6-C10-omega-dicarboxylic aciduria and unexplained episodes of lethargy and unconsciousness. The total excretion of adipic, suberic and sebacic acid ranged from 0.77 to 1.3 mg/mg creatinine after episodes of acute attack of the disease. Suberylglycine, identified by gas chromatography/mass spectrometry, was repeatedly found in the urine samples. The amount of this conjugate ranged from 0.2 to 0.5 mg/mg creatinine. The precursors of the dicarboxylic acids are suggested to be long chain monocarboxylic acids, oxidized through omega- and beta-oxidation to adipic, suberic and sebacic acid. Suberylglycine is subsequently formed by glycine-N-acylase catalyzed conjugation.     

Longitudinal study of the excretion of 1-hydroxypyrene in urine after external treatment with coal tar

This paper presents an analysis of the interactions among multiple human bodies, modeled by multilayered cylinders, exposed to microwaves. Cylinders are used because it is very difficult to compute the whole-body average specific absorption rate (SAR) at higher frequencies using a realistic human model. The average SAR is numerically discussed for a typical case of the linear array of two and three adult body models when the wave is vertically incident to the array.     

Breath hydrogen excretion by healthy cats after oral administration of oxytetracycline and metronidazole

Breath hydrogen excretion over a period of three hours was measured to evaluate carbohydrate malassimilation in healthy cats treated orally with antibiotics. Both an absorbable carbohydrate (xylose) and a non-absorbable carbohydrate (lactulose) were administered during the tests to evaluate the changes in the intestinal mucosa and the population of bacteria within the intestinal lumen. Overall, the effects of oxytetracycline and metronidazole on breath hydrogen excretion were not significantly different. However, the treatment effect with an antibiotic did significantly change breath hydrogen excretion after xylose administration (P < 0.05) within groups. Similarly, with each antibiotic, breath hydrogen excretion was affected significantly (P < 0.001) by the time after the administration of the carbohydrate. Treatment with each antibiotic also interacted significantly with this time effect (P < 0.05) within groups. After lactulose administration, there was a trend within groups for the type of antibiotic to interact with the treatment effect on breath hydrogen excretion (P = 0.09). After oxytetracycline treatment, more hydrogen was exhaled during the first 120 minutes after lactulose administration than in the pre-antibiotic test, whereas after metronidazole treatment, less hydrogen was exhaled between 60 and 180 minutes after lactulose, administration. After treatment with either oxytetracycline or metronidazole, more hydrogen was exhaled after xylose administration. Obligate anaerobes could be isolated from samples of small intestinal fluid obtained endoscopically after oxytetracycline treatment, but they could not be isolated after treatment with metronidazole.     

Ceftezole, a new cephalosporin C derivative II. Distribution and excretion in parenteral administration

The distribution of ceftezole in blood and tissues and its excretion after intramuscular or intravenous administration of single doses of 10 and 20 mg/kg were compared with those of cefazolin, cephaloridine and cephalothin. Blood levels of ceftezole in rats and rabbits were lower than those of cefazolin, and higher than those of cephaloridine and cephalothin. Retention time of ceftezole in the blood was somewhat shorter than that of cefazolin. However, blood levels of ceftezole in dogs were nearly the same as those of cefazolin and cephaloridine. The rate of urinary excretion of ceftezole in 24-hour urine after administration in rats and rabbits was found to be higher than those of the other antibiotics tested. In dogs, however, the rate of urinary excretion of ceftezole was nearly the same as that of cefazolin and higher than those of cephaloridine and cephalothin. The biliary excretion of ceftezole in rats and dogs was much higher than those of cephaloridine and cephalothin, but lower than that of cefazolin. Tissue distribution of ceftezole in rats was compared with that of the other antibiotics by intramuscular and intravenous administration. The initial level of ceftezole in the kidneys was found to be substantially higher than those of the other antibiotics. The initial level of ceftezole in the liver and lungs was also slightly higher than those of the other drugs when administered intramuscularly. Tissue levels of ceftezole were somewhat lower than those of cefazolin in rabbits after intravenous administration. Ceftezole attained a higher maximum level in rat lymph by intramuscular administration than the other antibiotics tested. The maximum concentration of ceftezole present in the exudate in the rat inflammatory pouch was higher than that of cefazolin. In rabbits with cerebrospinal meningitis induced by infection of Streptococcus pyogenes, the level of ceftezole in the cerebrospinal fluid was several times higher than that in normal rabbits. The serum level and urinary excretion of ceftezole was examined in 6 healthy male volunteers after intramuscular administration of a single dose of 500 mg. Ceftezole attained a mean maximum serum level of 22.9 mug/ml 30 minutes after administration and disappeared from the blood in about 6 hours. It was excreted rapidly in the urine. The concentration in 1-hour urine was the highest (mean level: 2,667 mug/ml) and the total excretion rate was 92.6%. No metabolites with antimicrobial activity were observed in the urine. No changes in the pattern of plasma level and urinary excretion and no accumulation in the tissues were observed after repeated intramuscular administration of 20 mg/kg of ceftezole in rabbits, 26 times, for 14 days.     

Reduced mercury excretion with feces in germfree mice after oral administration of methyl mercury chloride

When methyl mercury chloride was administered orally the amount of mercury excretion with feces of germfree mice was noticeably lower than that of the control mice. Germfree mice excreted 24 percent of the administered mercury within 10 days of administration while the control mice excreted 46 percent. Mercury retention in the organs of germfree mice was slightly higher than in the control mice. These results suggest that the existence of microorganisms in animal intestines are concerned with mercury excretion in the animal body.     

Time-course changes in blood pressure, urinary excretion of norepinephrine and dopamine after administration of fusaric acid in a single dose in elderly hypertensive patients

Time-course changes in blood pressure, urinary norepinephrine and dopamine excretion after administration in a single dose of fusaric acid calcium salt were examined in 8 elderly hypertensive patients. Eight elderly hypertensive patients served as controls receiving placebo administration in a single dose. The dose of fusaric acid calcium salt ranged from 5.1 mg/Kg to 6.0 mg/Kg. The results obtained are as follows: 1) Both systolic and diastolic blood pressure showed a significant reduction in fusaric acid calcium salt group, the lowest value of systolic blood pressure being observed from 4 to 8 hrs. and that of diastolic blood pressure being observed from 4 to 6 hrs. after administration of this agent, respectively. Systolic blood pressure returned more slowly to the level before fusaric acid calcium salt administration than diatolic blood pressure did. In placebo group, however, no significant reduction of both systolic and diastolic blood pressures was noted. 2) In fusaric acid calcium salt group, norepinephrine excretion in the urine did not show a diurnal change. In placebo group, however, a tendency of diurnal change was noted. These results would suggest that noepinephrine synthesis might be inhibited temporalily by fusaric acid calcijm salt. 3) In fusaric acid calcium salt group, dopamine excretion in the urine did hardly show a diurnal change. In placebo group, however, a fairly evident diurnal change was observed. The interpretation of these results seems to be difficult in the present state of knowledge of the action of fusaric acid calcium salt in humans.     

Sodium oxacillin in the horse: serum, synovial fluid, peritoneal fluid, and urine concentrations after single-dose intramuscular administration

Six healthy adult mares were given a single dose (25 mg/kg of body weight) of sodium oxacillin IM. Oxacillin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum oxacillin concentration was 9.75 microgram/ml at 0.5 hour after injection. Mean peak oxacillin concentrations in synovial and peritoneal fluids were 1.45 microgram/ml and 2.60 microgram/ml at 1 hour and 2 hours, respectively. These concentrations decreased in parallel with serum values and were not measurable at 48 hours. Urine concentrations of oxacillin were high, with a mean peak concentration of 2,790.2 microgram/ml at 0.5 hour.     

Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes

BACKGROUND & AIMS: Germander was withdrawn from the market after its use for weight control caused an epidemic of hepatitis. Its toxicity was shown to be caused by diterpenoids and their cytochrome P4503A-mediated metabolic activation into electrophilic metabolites that deplete cellular thiols. The aim of the present study was to determine the mechanisms of cell death. METHODS: Isolated rat hepatocytes were incubated for 2 hours with germander diterpenoids (100 micrograms/mL). RESULTS: Diterpenoids decreased cell glutathione, increased cytosolic [Ca2+], activated Ca(2+)-dependent tissue transglutaminase forming a cross-linked protein scaffold, and caused internucleosomal DNA fragmentation and the ultrastructural features of apoptosis. Cell death was prevented by decreasing metabolic activation (with troleandomycin), preventing depletion of glutathione (with cystine), blocking activation of Ca(2+)-modulated enzymes (with calmidazolium), or inhibiting internucleosomal DNA fragmentation (with aurintricarboxylic acid). Apoptosis was increased and diterpenoids caused overexpression of p53 and interleukin 1 beta-converting enzyme in rats treated with dexamethasone (cytochrome P4503A inducer). Apoptosis was also increased by a diet deficient in sulfur amino acids. CONCLUSIONS: The germander furano diterpenoids cause apoptosis within 2 hours in isolated rat hepatocytes. Electrophilic metabolites may stimulate apoptosis by decreasing thiols, increasing [Ca2+], and activating Ca(2+)-dependent transglutaminase and endonucleases.     

Identification of drug glucuronides in human urine by RP-HPLC after derivatization

The reactivity of nitric oxide under a given condition is a complex function of its diffusivity and the concentration of reacting partners. Quenching by NO of luminescence from Ru and Pd chelates of mesoporphyrin IX, two molecules which exhibit phosphorescence at room temperature, was utilized to evaluate the gas concentration and apparent diffusion coefficients. The properties of Ru-mesoporphyrin, a dye not previously employed as a probe for O2 or NO, were determined and the assay was verified and used to quantify NO produced by decomposition of nitrosocysteine. The pseudo-second order quenching constants were obtained from Stern-Volmer plots measured under various conditions and used to calculate diffusion coefficients for nitric oxide in solutions, proteins and membranes. The diffusion coefficients were greater at 37 than at 25 degrees C and, at a given temperature, smaller in proteins and membranes than in water. The conclusion is that NO and O2 closely resemble each other in diffusivity but that NO is slightly less lipophilic, resulting in somewhat faster apparent diffusion in protein and slower diffusivity in lipid, relative to O2. Taking a mean diffusion coefficient for NO of 10(-7) cm2s-1, then within 10 s the mean path is 10(-3) cm, or less than the diameter of a single cell. However, at low NO and O2 concentrations, the halflife of NO will be considerably longer than 10 s, and consequently the path of NO diffusion much greater.     

Metabolites of ebrotidine, a new H2-receptor antagonist, in human urine

The clinical application of ultrasonographic contrast agents in colour Doppler flow imaging of hepatic tumours is receiving increasing attention. Levovist is a suspension of galactose microparticles that provides reproducible concentrations of stabilized air bubbles with transpulmonary stability. Its effect on colour Doppler imaging was assessed in 26 patients with colorectal cancer and histologically proven hepatic metastases. Colour Doppler flow imaging was performed before and after intravenous injection of 10 ml Levovist 300 mg/ml. At 5-10 s after injection there was significant enhancement of the hepatic lesions with colour Doppler signals in 23 patients, lasting for a mean(s.d.) of 180(45) s. A consistent pattern of colour Doppler signal was observed, with increased enhancement predominantly around the tumour periphery and little or no central enhancement. These data suggest that Levovist may increase the sensitivity and specificity of colour Doppler flow imaging of colorectal hepatic metastases.     

Complementary medicine: a review of immunomodulatory effects of Chinese herbal medicines

Normal aging selectively impairs some forms of learning. For example, aging rabbits require more than twice as many trials to acquire 500-ms trace eyeblink conditioning than do young rabbits. N-methyl-D-aspartate (NMDA) receptor antagonists also impair trace conditioning. The effects of daily D-cycloserine (DCS; a partial agonist of the NMDA receptor-glycine site) treatment were tested on trace conditioning of young or aging rabbits using a conservative quantitative approach. DCS dose dependently improved acquisition, maximally reducing trials to criterion by approximately 50%. Dose-response curves were right-shifted by aging (twice the dose was required to achieve the same enhancement compared with controls). DCS did not affect nonassociative performance but sharpened the conditioned stimulus tone intensity discrimination. DCS thus can functionally modulate NMDA receptors in normal aging, enhance associative learning at all ages, and reduce or reverse age-dependent learning deficits.     

Detection and determination of theobromine and caffeine in urine after administration of chocolate-coated peanuts to horses

BACKGROUND AND OBJECTIVES: Most patients with colorectal liver metastases are not eligible for resection because they have multiple lesions or because of anatomical constraints. We report the use of cryotherapy to destroy residual metastases following liver resection in patients with disease too widespread for treatment by resection alone. METHODS: Twenty patients with bilobar disease confined to the liver (median 3; range 2-8 lesions) were treated in this way. Seventeen patients also received regional chemotherapy postoperatively. RESULTS: Morbidity was high, but there were no procedure-related deaths and only one patient's hospital stay exceeded 24 days. Significant destruction of tumor, as evidenced by a decline in CEA levels, occurred within 3 months of surgery in all patients (P < 0.001). Median duration of follow-up was 15 (6-53) months. Survival rates at 1 and 2 years were 88% and 60%, respectively, and median survival was 32 months. Seven patients remain well and seven are alive with recurrent liver and/or other metastases. CONCLUSIONS: Although this is not a control study, it would appear that some patients with irresectable liver metastases benefit from this multimodality approach.