Antibacterial activity of ofloxacin in urine for 4 days after a single oral dose of 400 mg

Antibacterial activity of ofloxacin in urine after a single oral dose of 400 mg was evaluated in ten healthy female volunteers. Urine was collected over six periods, i.e., 0-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, and 72-96 h postdose. Ofloxacin levels were assayed in all samples using a microbiological method and HPLC. Urinary ofloxacin MICs were determined for five bacterial strains recovered from urine, two E. coli strains of which one was susceptible and the other resistant to nalidixic acid (Nal-A), one Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), one Staphylococcus saprophyticus strain, and one Enterococcus faecalis strain; MICs were 0.06, 0.25, 1, 0.25, and 2 mg/L, respectively. Mean urinary ofloxacin levels by the microbiological method during the six collection periods were 193.3 +/- 30.3, 138.1 +/- 31, 53.2 +/- 7.3, 8.3 +/- 0.8, 1.4 +/- 0.2, and 0.6 +/- 0.1 mg/L, respectively. HPLC provided similar results: 216.7 +/- 31.6, 130.7 +/- 20.5, 56.5 +/- 7.1, 8.3 +/- 0.9, 1.5 +/- 0.3, and 0.5 +/- 0.05 mg/L, respectively. Mean urinary ofloxacin excretion over 96 h was 67.4 +/- 3.6% of the dose by the microbiological method was 72.5 +/- 2.5% of the dose by HPLC. On the first day, bacteriostatic activity of urine against enterobacteria exceeded 32 and was greater than 8192 for the nalidixic acid-susceptible E. coli strain; on the next day, overall values were equal or greater than 8 for the nalidixic acid-resistant E. coli and K. pneumoniae strains. Bacteriostatic activity was equal to or greater than 32 for the S. saprophyticus strain during the first two days and equal to 8 on the first day and 4 on the second day for the E. faecalis strain.     

Dissolved Oxygen Downstream of an Effluent Outfall in an Ice-Covered River: Natural and Artificial Aeration

In ice-covered rivers, dissolved oxygen (DO) might fall below critical levels for aquatic biota in the absence of surface aeration, combined with low winter flow conditions and reduced photosynthesis rates. Open-water zones, however, can be created downstream of a diffuser by warm effluent discharges, resulting in an increase in surface aeration. In this study, we modeled the behavior of the effluent plume and the resulting open-water lead development in the Athabasca River, Alberta, Canada downstream of a pulp mill diffuser. The DO was found to increase by 0.26?mg/L due to surface aeration of an open-water lead of 6.07?km. We also evaluated oxygen injection into the effluent pipeline to increase the DO in the river. At an injection rate of 3,500 and 5,000?lb/day of liquid oxygen, the DO was increased by 0.16 and 0.21?mg/L, which corresponded to an absorption efficiency of about 50%. The artificial aeration technique evaluated here appears to be an effective alternative to increase DO levels in ice-covered rivers. The results of this study are important in developing accurate DO models for ice-covered rivers and in evaluating oxygen injection systems.     

Stimulating In Situ Hydrogenotrophic Denitrification with Membrane-Delivered Hydrogen under Passive and Pumped Groundwater Conditions

A technology was developed to stimulate autotrophic biological denitrification by supplying hydrogen (H2) to groundwater via gas-permeable membranes. The purpose of this project was to investigate this technology at field scale, determining whether it could be successfully scaled up from the laboratory. The field site was located in Becker, Minnesota and contained high levels of NO3? (22.8±2.0?mg/L-N) and dissolved oxygen (DO) (7±1?mg/L). Membranes installed in groundwater wells were successful in delivering H2 to the groundwater over the two-year operating period. Hydrogen stimulated microbial reduction of DO and NO3?, degrading up to 6 mg/L DO and converting up to 10.0 mg/L NO3?-N to NO2?-N when operated passively. When recirculation pumps were installed performance in the field did not improve significantly because of mixing with more oxygenated water. However, complementary modeling studies showed that complete DO reduction and denitrification to N2 was possible but the zone of influence and total H2 demand were limiting factors. Water was recirculated in the field from downgradient to upgradient membrane-containing wells to increase the H2 delivery through the membrane by an increase in water velocity. The depth to groundwater ( ～ 13.7?m) caused some water reoxygenation during recirculation, which may preclude the use of this technology at deep sites, as this makes it more difficult to install sufficient wells and control recirculation.     

Neuroprotective effects of NPS 846, a novel N-methyl-D-aspartate receptor antagonist, after closed head trauma in rats

OBJECT: The authors sought to determine whether 3,3-bis (3-fluorophenyl) propylamine (NPS 846), a novel noncompetitive N-methyl-D-aspartate receptor antagonist, alters outcome after closed head trauma in rats. METHODS: The experimental variables were: presence or absence of closed head trauma, treatment with NPS 846 or no treatment, and time at which the rats were killed (24 or 48 hours). The NPS 846 (1 mg/kg) was administered intraperitoneally at 1 and 3 hours after closed head trauma or sham operation. Outcome measures were the neurological severity score (NSS), ischemic tissue volume, hemorrhagic necrosis volume, and specific gravity, water content, and concentrations of calcium, sodium, potassium, and magnesium in brain tissue. The following closed head trauma-induced changes in the injured hemisphere (expressed as the mean +/- the standard deviation) were reversed by NPS 846: decreased specific gravity of 1.035 +/- 0.006 at 24 hours was increased to 1.042 +/- 0.004; the decreased potassium level of 0.583 +/- 0.231 mg/L at 48 hours and at 24 hours was increased to 2.442 +/- 0.860 mg/L; the increased water content of 84.7 +/- 2.6% at 24 hours was decreased to 79.8 +/- 2%; the increased calcium level of 0.592 +/- 0.210 mg/L at 24 hours was decreased to 0.048 +/- 0.029 mg/L; and the increased sodium level of 2.035 +/- 0.649 mg/L was decreased to 0.631 +/- 0.102 mg/L. Administration of NPS 846 also lowered the NSS (improved neurological status) at 48 hours (7 +/- 3) and caused no significant changes in ischemic tissue or hemorrhagic necrosis volumes in the injured hemisphere at 24 or 48 hours. CONCLUSIONS: In this model of closed head trauma, NPS 846 improved neurological outcome, delayed the onset of brain edema, and improved brain tissue ion homeostasis.     

Which androgen replacement therapy for women?

Although the postmenopausal ovary remains an important source of testosterone (T) production, there is nevertheless a decline in total circulating androgen levels with age. A role for androgen replacement in addition to estrogens in some postmenopausal, particularly ovariectomized, women is increasingly gaining acceptance. We have compared the pharmacokinetics of two existing testosterone preparations, oral testosterone undecanoate (TU) and sc testosterone implants, with a new matrix transdermal delivery system for T. In study 1, three different doses of TU (40 mg, two 20-mg doses 6 h apart and two 10-mg doses 6 h apart, orally) were investigated in 10 postmenopausal women. Median peak levels of 18 nmol/L (range, 5.8-64.0 nmol/L; 40 mg), 12.3 nmol/L (range, 5.7-29.2 nmol/L; 20 mg), and 9.7 nmol/L (range, 7.8-28.7 nmol/L; 10 mg) were observed, but T levels varied considerably within and between subjects regardless of the dose used. In study 2, 30 women receiving s.c. estradiol therapy were randomized to receive either a 100-mg T implant or placebo. In the T-treated group, levels peaked at 8.9 +/- 1.7 nmol/L 1 month after insertion and then declined gradually to 2.9 +/- 0.4 nmol/L at 6 months. In study 3, a novel matrix transdermal delivery system for T was investigated in 6 females. Estimated daily delivery rates of 840 (TD 1), 1100 (TD2), and 3000 microg (TD3) T/24 h were investigated. T rose rapidly after a single application of TD 1 and TD2 and were relatively constant for the next 18 h, at which time peaks of 2.3 +/- 1.0 and 4.1 +/- 1.6 nmol/L, respectively, at 24 h were seen. T concentrations fell to baseline levels within 6 h after patch removal. When TD2 was applied for 7 days, a T level of 4.3 +/- 0.7 nmol was seen 24 h after application, falling gradually to 2.8 +/- 0.7 nmol/L by day 7. During twice weekly application of TD2, stable T concentrations were maintained, and all peak levels were similar (peak level, 4.2 +/- 0.3 nmol/L 24 h post-TD application) as were predose troughs (3.2 +/- 0.3 nmol). Twice weekly application of TD3 produced a similar pattern of T, and the mean peak and trough levels were 7.5 +/- 0.9 and 4.0 +/- 0.4 nmol/L, respectively. In conclusion, TU produced inappropriate high T levels at all doses, with wide variations between subjects, confirming that TU is unpredictably absorbed and unlikely to be satisfactory for use in women. Subcutaneous testosterone implants produce unphysiological T levels for at least 1-2 months. The transdermal matrix delivery system maintained relatively stable T levels within narrow ranges with little within- and between-subject variation. We conclude that such transdermal systems may be of value for androgen therapy in postmenopausal women because they provide a highly controllable way of delivering T noninvasively and reliably, and achieve mean physiological levels not possible with existing methods.     

Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed rats

N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.     

Concentration of teicoplanin in the serum of adults with end stage chronic renal failure undergoing treatment for infection

We examined the adequacy of the following schedule for the administration of i.v. teicoplanin to patients with chronic renal failure: three doses of 6 mg/kg at 12 h intervals, a fourth dose 24 h later and then subsequent doses every 72 h. Eight infected patients undergoing dialysis were investigated, with serum antibiotic concentrations measured ten minutes before and one hour after administration. Mean trough concentrations were 6.9 +/- 3.1 mg/L on day two, 9.8 +/- 4.4 mg/L (day three), 9.2 +/- 4.8 mg/L (day six), 10.9 +/- 5.5 mg/L (day nine), 12.1 +/- 6.1 mg/L (day 12) and 14.8 +/- 8.0 mg/L (day 15). The proposed schedule achieved adequate trough serum teicoplanin concentrations by 48 h in six out of eight patients examined. The dosage regimen was well tolerated.     

Effect of Aeration on the Quality of Effluent from UASB Reactor Treating Sewage

The treatment of effluent of pilot- and full-scale upflow anaerobic sludge blanket (UASB) reactors operating at steady state was studied in an aeration-settling system. The fine pore submerged diffusers were used to aerate the effluent of UASB reactors under different operating conditions. Forty to 55% of the biochemical oxygen demand (BOD) and the chemical oxygen demand (COD) removal efficiencies were achieved by the direct aeration of the UASB effluent in the laboratory. The maximum removal efficiencies were achieved at 30?min hydraulic retention time (HRT) and a dissolved oxygen (DO) of 5–6??mg/L or high KLa (vigorous aeration). Batch experiments on nitrogen purging and the aeration of sulfides, volatile organic compounds (VOCs), and nonpurgeable organic carbons (NPOCs) were performed to ascertain the mechanism of BOD/COD removal. During aeration, BOD and COD were reduced by the stripping of H2S and VOCs and by the chemical oxidation of total sulfides and organic carbon. The stripping and chemical oxidation depended on the HRT and DO. The performance of a full-scale surface aeration system was compared to the performance of a pilot-scale diffused aeration system. Final sedimentation was effective only in removing the solids from the effluent of the aeration system. The results were confirmed by organic mass balance.     

Disposition of the selective alpha1A-adrenoceptor antagonist tamsulosin in humans: comparison with data from interspecies scaling

Tamsulosin-HCl is an alpha1A-adrenoceptor antagonist that is mainly eliminated by metabolism in animals and humans and is highly bound to alpha1-acid glycoprotein in blood plasma. The disposition of the compound (0.4 mg as modified-release granules in a capsule) was determined in male volunteers, using intravenous (iv) infusion of tamsulosin-HCl (0.125 mg over 4 h) as reference treatment for the assessment of absolute oral bioavailability. Disposition parameters of iv tamsulosin in humans was compared with data predicted from animal data by interspecies scaling techniques. Levels after iv dosing in humans showed a biexponential decline, with mean half-lives (+/-SD) of 1.2 +/- 0.6 and 6.8 +/- 3.5 h, respectively. The mean systemic clearance (+/-SD) was low (viz., 48 +/- 24 mL/min). The mean volume of distribution (+/-SD) was rather small (21 +/- 6 L), and was estimated at 16 +/- 4 L in the steady state. The mean absolute oral bioavailability (+/-SD) was approximated at 100 +/- 19%. Systemic clearance in humans was poorly predictable from a logarithmic clearance versus body weight relation of rat, rabbit, and dog data. The prediction improved dramatically (accuracy 213%) when scaling was done with systemic clearance values of unbound drug, and it improved further (accuracy 59%) with the product of unbound clearance and maximum life-span potential. Also, the prediction of volume of distribution improved dramatically (accuracy 81%) after correction for differences in extent of protein binding between species. The terminal disposition half-life of 7.0 h, as predicted after integrating maximum life-span potential and protein binding in scaling of clearance, was very close to the value of 6.8 h established experimentally in humans. The present results with tamsulosin underline the importance of correction for extent of protein binding in allometric scaling of clearance and distribution volume.     

Should benefit-risk ratio of the intramuscular vitamin K be reevaluated in newborn infants?

AIM: To compare the pharmacokinetics after po different doses of beta-carboxyethylgermanium sesquioxide (Ge-132). METHODS: An atomic absorption spectrophotometric system was used to measure germanium concentrations in plasma and urine samples after po Ge-132 1 (low dose, LD), 2.5 (medium dose, MD), and 4 (high dose, HD) g.m-2 in 24 healthy volunteers (one dose per 8 subjects). RESULTS: T1/2 alpha (LD, 1.2 +/- 0.7 h; MD, 1.1 +/- 0.6 h; HD, 1.2 +/- 0.5 h), T1/2 beta (LD, 5.2 +/- 1.2 h; MD, 5.8 +/- 2.5 h; HD, 5.5 +/- 1.4 h) and Cl/F (LD, 33 +/- 12 L.h-1; MD, 35 +/- 10 L.h-1; HD, 33 +/- 11 L.h-1) were not dose-related. Tmax was between 0.75 h and 2 h. Cmax (LD, 5.3 +/- 2.2 mg.L-1; MD, 13 +/- 5 mg.L-1; HD 18 +/- 8 mg.L-1, HD) and AUC (LD, 31 +/- 13 mg.h.L-1; MD, 60 +/- 16 mg.h.L-1; HD, 79 +/- 42 mg.h.L-1) were positive correlation to the dose of Ge-132. Urine-eliminated germanium within 24 h accounted for 11 +/- 3% of LD, 9 +/- 3% of MD, and 6 +/- 5% of HD (calculated from Ge/F) and showed a negative correlation to the dose. CONCLUSION: 1) Intracorporal process of Ge after po Ge-132 coincided with the first-order absorption and elimination with two-compartment kinetic model; 2) The amount of germanium eliminated in urine was below 11%.     

Comparative Absorption of Crude Oil from Fresh and Marine Water Using Recycled Rubber

Crude oil spillage is a major environmental pollution in the Niger–Delta area of Nigeria. The use of recycled rubber from enormous available scrap tires for pollution control of oil-polluted fresh and marine water and the attendant survival of aquatic organisms (fish) in these polluted waters was investigated. The absorption capacity of rubber particles for the oil was the same in both the oil-polluted fresh and marine waters and depended on the rubber particle size and temperature of absorption. The survival time of the fish depended on the amount of rubber added to and the dissolved oxygen (DO) concentration in the oil-polluted waters. The survival time increased from 3.5 to 7.25?h as the rubber to oil ratio was increased from 0.5 to 2.5. At a ratio of 3, the oil film on the water was no longer continuous and the survival time increased to 6,000?h. The survival time increased with the DO concentration in polluted water. In the absence of added rubber particles, the DO concentration decreased within 2?h from 5.27?mg/L to less than 3?mg/L, a value below the limit required for aquatic organism survival.     

Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in nephrotoxic nephritis, a model of human rapidly progressive glomerulonephritis. To evaluate the pathogenetic relevance of ICAM-1 in this model, nephrotoxic nephritis was induced in ICAM-1 knockout mice and genetic controls. Mice were preimmunized with rabbit IgG in complete Freund's adjuvant. Seven days later they received rabbit anti-mouse glomerular basement membrane IgG. The early humoral immune responses (levels of circulating mouse anti-rabbit IgG, glomerular deposition of rabbit and mouse IgG and mouse C3c) were not altered in ICAM-1 knockout mice. During 28 d of follow-up, 3 of 19 control nephritic mice and 0 of 16 ICAM-1 knockout mice died. Proteinuria was high in nephritic control mice (means 10 to 12 mg/24 h at all time points investigated) and significantly reduced in nephritic ICAM-1 knockout mice (means <4.4 mg). Mean serum creatinine rose from 29 micromol/L at day -7 to 48 micromol/L (day 28) in nephritic control mice. This increase in serum creatinine was significantly lower in ICAM-1 knockout mice: 27 (day -7) and 36 micromol/L (day 28). Histologic analysis at day 28 revealed that ICAM-1 deficiency in nephrotoxic nephritis mice led to significantly reduced glomerular crescent formation (2+/-3% in ICAM-1 knockout mice versus 13+/-8% in nephritic controls) and tubulointerstitial injury (score 0.4+/-0.4 versus 2.0+/-1.1). By immunohistochemistry, ICAM-1 deficiency in nephritic mice led to significantly reduced (peri-)glomerular and/or interstitial macrophage influx, alpha-smooth muscle actin expression, and type IV collagen accumulation. These data indicate that ICAM-1 is a central mediator of glomerular and tubulointerstitial injury in murine nephrotoxic nephritis.     

Evaluation of Electric Arc Furnace Slag as a Potential Phosphate-Removal Substrate

A study was conducted to evaluate the performance of locally available electric arc furnace slag (EAFS) as a substrate for removing phosphorus from wastewater. First, in a laboratory study, EAFS was found to have high phosphorus removal efficiency for three P concentrations (0.3, 3.0, and 6.0 mg/L); this resulted in nearly 100% phosphorus removal in 24 h. Next, the experiment was repeated using aeration and similar phosphorus removal was observed but in a shorter contact time of 1 h. The adsorption capacity of EAFS was determined to be 1,458 mg/kg. In a pilot-scale study, over 90% P removal took place in the first 4 h under nonaerated conditions, and nearly 100% removal in 8 h. While the P removal with aeration was relatively less initially for the shorter residence times, a 100% removal was observed for the 24-h residence time.     

Pharmacokinetics of orally administered estradiol valerate. Results of a single-dose cross-over bioequivalence study in postmenopausal women

A randomized, single-dose cross-over study in 32 postmenopausal women was performed to demonstrate bioequivalence of two estradiol valerate containing formulations (first sequence of Klimonorm as test preparation). The serum levels of estradiol, free and conjugated estrone were measured until 48 h after an oral dosage of 4 mg estradiol valerate (CAS 979-32-8). The mean AUC(0-48) of estradiol was calculated as 1006.6 +/- 479.4 h x pg x ml-1 (Test) and 1015.2 +/- 555.2 h x pg x ml-1 (Reference). The corresponding (AUC(0-48) of the active metabolite, free estrone, exceeded that of estradiol at 3578.3 h x pg x ml-1 (Test) and 3485.1 h x pg x ml-1 (Reference). Much higher was the AUC(0-48) for conjugated estrone at 132.4 h x ng x ml-1 (Test) and 133.6 h x ng x ml-1 (Reference). Mean estradiol Cmax values of 39.8 +/- 17.7 pg/ml (Test) and 42.9 +/- 21.0 pg/ml (Reference) were attained 8.2 +/- 4.5 h (Test) and 10.0 +/- 5.9 h (Reference) after the administration of 4 mg estradiol valerate. Maximal free estrone concentrations of 163 pg/ml (Test) and 174.3 pg/ml (Reference) were reached after 7.2 h (Test) and 7.5 h (Reference). Maximal conjugated estrone concentrations of 15.5 ng/ml (Test) and 16.2 ng/ml (Reference) were reached after 2.4 h (Test) and 2.0 h (Reference). The terminal elimination half-life of estradiol was calculated at 16.9 +/- 6.0 h (Test) and 15.0 +/- 4.8 h (Reference), that of free estrone at 16.3 h (Test) and 13.5 h (Reference), that of conjugated estrone at 11.8 h (Test) and 10.6 h (Reference). After logarithmic transformation, the 90% confidence intervals of the AUC(0-48) and Cmax ratios for estradiol and also for the metabolites (free and conjugated estrone) were within the acceptance ranges for bioequivalence. Therefore the test preparation and the reference preparation are bioequivalent.     

The effect of asphyxia on the pharmacokinetics of ceftazidime in the term newborn

The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated term infants with suspected septicemia on d 3 of life. Nine term infants with suspected septicemia but without asphyxia served as controls. Blood samples were collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v. bolus injection. A high performance liquid chromatography method was used to determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one-compartment open model. The GFRs of all infants were simultaneously studied by means of the 24-h continuous inulin infusion technique. Elimination serum half-life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46 +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ were significantly (p < 0.001) increased in the asphyxiated newborn, whereas total body clearance of CAZ (128.4 +/- 25.1 mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg versus 60.8 +/- 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43 versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxiated newborn. We conclude that twice daily administration of 50 mg/kg of body weight CAZ given to asphyxiated term newborns in the first days of life results in significantly higher serum trough levels in comparison with control infants. The impaired CAZ clearance is a result of a significantly decreased GFR.     

HMBR法处理某黄金矿山氨氮废水试验研究

针对某黄金矿山外排水氨氮浓度较高的特点,采用复合式膜生物反应器(HMBR)系统进行处理。研究了在好氧区pH为弱酸性及中性条件下,HMBR法对氨氮和COD等典型污染物的去除特征。试验确定了HMBR法最佳工艺参数:好氧区pH值控制为6.80~7.20,DO为2~3 mg/L,动态曝气运行周期6 min(运行-间歇时间4 min^-2 min),在线化学清洗措施为“柠檬酸+水-次氯酸钠”,水力停留时间为2.34 d,HMBR出水中氨氮和COD均达到GB 8978—1996《污水综合排放标准》一级要求。该研究为HMBR法处理氨氮废水的工业化应用提供数据支持。     

Histamine-2 receptor antagonists do not alter serum ethanol levels in fed, nonalcoholic men

OBJECTIVE: To determine whether the four histamine-2 receptor antagonists currently available for the treatment of acid-peptic disorders in the United States alter serum ethanol levels after moderate alcohol consumption. DESIGN: Prospective, randomized crossover design comparing the effects of histamine-2 receptor antagonists and no treatment on serum ethanol levels. Each participant served as his own control. PARTICIPANTS: Twenty-five healthy nonalcoholic men (21 to 35 years old); two participants were withdrawn before starting the study. SETTING: University medical center. INTERVENTION: Cimetidine (400 mg twice daily), famotidine (20 mg twice daily), nizatidine (150 mg twice daily), ranitidine (150 mg twice daily), and no treatment for 7 days. After the last dose of medication, participants ate a standard meal; 1 hour later they drank ethanol (0.3 g/kg body weight in 500 mL of orange juice) over 8 minutes. MEASUREMENTS: Simultaneous measurements of breath and serum (headspace gas chromatography) ethanol were made before and 10, 20, 30, 45, 60, 90, 120, 150, and 180 minutes after ingestion of ethanol. RESULTS: Peak ethanol levels did not differ (mmol/L; mean +/- SE) after cimetidine (3.0 +/- 0.3), famotidine (2.9 +/- 0.3), nizatidine (2.9 +/- 0.3), ranitidine (3.1 +/- 0.4), and no treatment (2.9 +/- 0.4). Similarly, there was no difference in the area under the curve (mmol/L.h; mean +/- SE) after cimetidine (4.3 +/- 0.5), famotidine (3.8 +/- 0.4), nizatidine (4.2 +/- 0.5), ranitidine (3.9 +/- 0.4), and no treatment (4.0 +/- 0.5). CONCLUSIONS: In healthy nonalcoholic men, the histamine-2 receptor antagonists currently available in the United States do not alter serum ethanol levels following moderate alcohol consumption after an evening meal.     

In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results

Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded.     

Involvement of ovarian kinin-kallikrein system in the pathophysiology of ovarian hyperstimulation syndrome: studies in a rat model

The purpose of the present study was to investigate a possible participation of the kinin-kallikrein system (KKS) in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Symptoms of hyperstimulation were produced in immature female rats using equine chorionic gonadotrophin followed by human chorionic gonadotrophin (HCG). At 48 h after the HCG injection, rats were injected s.c. with 100 microg/kg of HOE140, bradykinin-2 receptor antagonist. Capillary permeability was evaluated using peritoneal Evans blue dye (EB) concentrations 30 min after the i.v. injections. The EB concentrations in the hyperstimulated rats were significantly reduced 4 and 6 h after the HOE140 injection, compared with those injected with the vehicle as a control (4.58+/-0.80 versus 8.22+/-0.87 and 4.32+/-0.74 versus 8.35+/-1.03 microg respectively; P < 0.03), indicating the involvement of kinin in the pathophysiology of OHSS in this model. The administration of 10 IU aprotinin significantly reduced the peritoneal EB concentration when compared with the control (4.13+/-0.53 versus 7.95+/-1.06 microg; P < 0.01), implicating a possible role of kallikrein. Furthermore, pretreatment with RU486 (5 or 10 mg/kg) resulted in a significant reduction of ovarian kinin concentrations 48 h after the HCG injection, compared with the control (1.22+/-0.07 or 1.43+/-0.07 versus 1.94+/-0.10 pg/mg; P < 0.005 and P < 0.05 respectively). Similar results were obtained in the peritoneal EB concentrations. In addition, a significant correlation between the ovarian kinin and peritoneal EB concentrations was observed (P < 0.001, r = 0.539). Thus it was suggested that ovarian KKS plays an intermediary role in the progesterone-induced augmentation of capillary permeability in this experimental model, indicating the involvement of KKS in the pathophysiology of OHSS.     

Expression of the adenocarcinoma-related antigen recognized by monoclonal antibody 44-3A6 in salivary gland neoplasias

1. Renal specific targeting of the non-steroidal anti-inflammatory drug naproxen was obtained by coupling to the low-molecular-mass protein lysozyme. A previous study showed that conjugation to lysozyme resulted in a 70-fold increase of naproxen accumulation in the kidney with a subsequent renal release of the active metabolite naproxen-lysine.2. In the present study we questioned whether naproxen-lysozyme is active in the rat kidney, inhibiting the urinary excretion of prostaglandin E2 and renal sodium and water excretion in salt-restricted baseline conditions as well as during frusemide treatment.3.A high dose of free naproxen (10 mg.day-1. kg-1) did not affect prostaglandin E2 excretion in baseline conditions (naproxen, 11+/-1 ng/8 h; vehicle, 13+/-4 ng/8 h), whereas sodium and water excretion were, respectively, 3.0 and 1.6 times lower in the naproxen group (P<0.05). Naproxen completely prevented the frusemide-induced increase (3-fold) in prostaglandin E2 excretion (naproxen 6.6+/-1.1 ng/8 h, vehicle 40+/-12 ng/8 h, P<0. 005). Frusemide-stimulated natriuresis and diuresis were, respectively, 1.6 (P<0.05) and 1.8 times (P<0.005) lower in the naproxen group.4.A dose of 2 mg.day-1.kg-1 lysozyme-conjugated naproxen did not affect prostaglandin E2 excretion in baseline conditions (conjugate, 18+/-2 ng/8 h; vehicle, 24+/-5 ng/8 h). The conjugate also had no effect on sodium and water excretion. However, the naproxen conjugate completely prevented the frusemide-induced increase (2-fold) in prostaglandin E2 excretion (conjugate, 16+/-3 ng/8 h; vehicle, 48+/-13 ng/8 h, P<0.05). Surprisingly, frusemide-induced natriuresis and diuresis were not affected by the conjugate.5. In conclusion, a renal specific delivery of the non-steroidal anti-inflammatory drug naproxen using lysozyme results in an inhibitory effect on renal prostaglandin E2 synthesis but does not affect the excretion of sodium and water, in contrast to free naproxen.