The effect of cadmium on zinc absorption was studied using an isolated vascularly and luminally perfused rat intestinal preparation. 65Zn as well as Zn and Cd (both as the chloride salt) were added to the luminal perfusion medium (LPM) at varying concentrations. Over a 90-min period, the amount of Zn appearing in the vascular perfusion medium (VPM) and that retained by the tissue post-perfusion was estimated. Cd at all levels studied (0.03, 0.10, 1.0, and 10.0 micrograms/mL) reduced the amount of Zn appearing in the VPM in comparison with control perfusions (no detectable Cd in the LPM) when the initial Zn concentration was 5 micrograms/mL. Similarly, with an initial Zn concentration of 10 or 20 micrograms/mL, the amount of Zn appearing in the VPM was reduced when the Cd concentration was 0.1 or 1.0 micrograms/mL. With these same Zn concentrations, the amount of Zn retained by the tissue was higher when the Cd concentration was 10 micrograms/mL. These results demonstrate that Cd at low concentrations is capable of reducing Zn appearance in the VPM.

Animals↗

PubMedDate not supplied

Renal aluminum excretion.

Urinary aluminum (Al) excretion was studied in humans with normal and impaired renal function. Al was measured by atomic absorption spectrometry. In healthy volunteers (n = 50), renal Al excretion was 12.2 +/- 8.5 micrograms/24 h. Two patients on plasma exchange therapy with normal renal function and an inadvertent load of 870 and 388 micrograms Al/treatment showed a 23 and 14% positive balance until next treatment. The renal pathway of excretion was shown to be important in 6 chronic renal failure patients on continuous peritoneal dialysis with residual renal function who eliminated in 24 h 51.4 +/- 24.0 micrograms Al by urine and only 27.2 +/- 18.4 micrograms Al across the peritoneum following a daily oral application of 342 mg Al. Studies with the isolated perfused rat kidney confirmed the limited renal capacity to eliminate Al. Al clearance declined from 0.75 to less than 0.08 mL/min when the kidney was perfused with 0.04-12.4 micrograms Al/mL medium. Al content of the kidney increased in a dose-dependent manner from less than 0.05 to 4.4 micrograms/kidney and reached saturation at 5 micrograms Al/mL medium.

Adult↗

PubMedDate not supplied

Piperidine renin inhibitors: from leads to drug candidates.

Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status.

Animals↗

PubMedDate not supplied

Immune response in the early postoperative period after implantation of a left-ventricular assist device system.

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Adolescent↗

PubMedDate not supplied

Dietary intake of PCDD/F by small children with different food consumption measured by the duplicate method.

The dietary intake of PCDD/F by 42 small children, 21 boys and 21 girls in the age range 14-47 months, with different food consumption behaviour living in urban and rural areas of Germany was measured by the duplicate method with a 7 day sampling period from May to September 1998. The PCDD/F-levels in the food duplicates were in the range 39.2-325 fg I-TEq/g(dry weight) (median: 90.7; arithmetic mean: 96.6) and the doses were in the range 0.681-5.43 with a median of 1.56 and an arithmetic mean (AM) of 1.60 pg I-TEq/(kg(body weight) x d). Children living in an urban industrialized area with food consumption including products from the family owned vegetable gardens or the surrounding area and/or products from domestic animals showed no statistically significant different concentrations in the food duplicates or in the dietary intake of PCDD/F, calculated as I-TEq, than children living in a rural area with similar food consumption behavior or than children consuming exclusively food from the supermarket.

Animals↗

PubMedDate not supplied

Myeloperoxidase-catalyzed formation of PCDD/F from chlorophenols.

Chlorophenols (CP) are transformed in vitro to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) by a biochemical-catalyzed oxidation. This is shown for 2,4,5-tri-, 2,3,4,6-tetra-and pentachlorophenol with myeloperoxidase recovered from human leucocytes in the presence of hydrogen peroxide. The yield, the reaction, and the PCDD/F-pattern found depend on the CP. The formation rates are in the micromol-per-mol range for all substrates. The experiments confirm the suspicion that a biochemical formation of PCDD/F from precursors such as CPs can take place in the human body and that this metabolic pathway may lead to a higher inner exposure with PCDD/F than is now assumed.

Benzofurans↗

PubMedDate not supplied

Decrease of PCDD/F levels in human blood from Germany over the past ten years (1989-1998).

744 whole blood samples of normal subjects from Germany collected in 1989-1998 have been analyzed for polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) by capillary gas chromatography/high resolution mass spectrometry. Over the examined time period a continuous decrease of the PCDD/F concentrations in human blood was observed. The mean levels found were 43.7 pg I-TEq/g (lipid basis) in 1989 and 20.7 pg I-TEq/g (lipid basis) in 1996/98 [median: 42.2 and 19.4]. The reduction to about the half was found for most congeners. Each one-year subset of the collective and the entire collective shows a positive correlation of the PCDD/F blood levels with age for most of the congeners, the sum values and the calculated toxicity equivalents. For statistical evaluation a multiplicative model was used: Concentration = A x Age(B). The correlation is mostly pronounced for lower chlorinated PCDD and for 2,3,4,7,8-PentaCDF. The PCDD/F concentrations in human blood in relation to the year of examination and the age of the subjects can be described by a linear model: I-TEq [pg/g (lipid basis)] = 6176 - 3.097 x Year + 0.6482 x Age or by a multiplicative model: I-TEq [pg/g(lipid basis)] = 10(89.08-0.04415 x Year + 0.008468 x Age).

Adult↗

PubMedDate not supplied

Uptake of aluminum, cadmium, copper, lead, and zinc by human scalp hair and elution of the adsorbed metals.

Uptake of aluminum (Al), cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) from aqueous solutions by human scalp hair (water/hair = 100:1) has been studied in the concentration range 0-50 mg/L. Hair metal levels were determined by a wet digestion procedure and atomic absorption spectrometry. Under conditions used, uptake followed a sigmoid concentration-response relationship. The order of binding capacity of hair to the metals was as follows: Al greater than Cd greater than Cu greater than Pb greater than Zn. Using logit transformation 50% saturation was evaluated at the following metal concentrations (hair metal concentration of saturation is given in parenthesis): 0.34 mg/L for Al (0.154 mg/g); 1.82 mg/L for Cd (0.363 mg/g); 2.21 mg/L for Cu (0.651 mg/g); 2.52 mg/L for Pb (0.986 mg/g); 23.84 mg/L for Zn (1.616 mg/g). Percentage elution of trace metals from hair after treatment with metal-enriched solutions by five different procedures ranged from 14.5 to 46.5% for Al, from 11.1 to 28.9% for Zn, from 11.5 to 28.4% for Pb, from 8.9 to 13.6% for Cd, and from 0.1 to 11.8% for Cu. In addition, trace element concentrations were measured in tap water samples and shampoos.

Acetone↗

PubMedDate not supplied

Influence of storage conditions on aluminum concentrations in serum, dialysis fluid, urine, and tap water.

The influence of storage temperature, vessel type, and treatment on alterations of aluminum (Al) concentrations in serum, urine, and dialysis fluid samples was studied at three different concentrations for each sample over an 18-month period. Furthermore, the influence of acidification on Al levels in tap water, urine, and dialysis fluid samples was studied over a four-month period. Al was measured by atomic absorption spectrometry. Sample storage in glass vessels was unsuitable, whereas only minor alterations of Al levels were observed with storage in polypropylene tubes, polystyrene tubes, and Monovettes. By using appropriate plastic containers, acid washing of the vessels showed no improvement. Frozen storage was superior compared with 4 degrees C, whereas storage at -80 degrees C offered no advantage compared with storage at -20 degrees C. Acidification of tap water samples was necessary to stabilize Al levels during storage. No striking effect of acidification on Al levels in urine and dialysis fluid samples was found. It is concluded that longterm storage of serum, urine, tap water, and dialysis fluid samples is possible if appropriate conditions are used.

Aluminum↗

PubMedDate not supplied

HPLC with simultaneous UV and reductive electrochemical detection at the hanging mercury drop electrode: a highly sensitive and selective tool for the determination of benzodiazepines in forensic samples.

A versatile, sensitive, and selective high-performance liquid chromatographic (HPLC) procedure for the determination of common benzodiazepines and some of their most frequently occurring metabolites in forensic samples was developed and optimized with respect to effective and rapid sample preparation and high selectivity of the analytical assay. The optimized method includes liquid-liquid extraction of the drugs with chloroform followed by isocratic reversed-phase chromatography on a LiChrospher-100 RP-8ec column (150 x 4.6-mm i.d.) with a mobile phase consisting of 0.03 mol/L acetate buffer (pH 4.6)/acetonitrile (55:45, v/v). The use of dual-mode detection made up of UV-detection (250 nm) in series with reductive electrochemical detection (-1.4 V vs. Ag/AgCl) at the hanging mercury drop electrode permits the detection and quantitation of benzodiazepines even in degraded samples with higher selectivities than usually reached with conventional HPLC techniques. Depending on the actual benzodiazepine species, detection limits are in the range of 2.0 to 14.1 ng/mL. Mean recovery values of the drugs from blood range from 82 to 92%; within-day and day-to-day repeatabilities typically lie between 3 and 9%. Several case work examples demonstrate the high selectivity and remarkably low matrix sensitivity of the described assay.

Anti-Anxiety Agents↗

PubMedDate not supplied

European Surveillance of Infections in Cancer Patients--ESIC.

Major advances in cancer therapy result from development of multidrug chemotherapy regimens. Besides death from tumor progression, infections are currently one of the major causes of mortality and morbidity. Because of the risk of complications and mortality, the treatment for febrile neutropenia is admission to hospital and administration of broad-spectrum antibiotics. Response rates of initial antimicrobial treatment vary considerably (40-92%). Due to the heterogeneity of populations in randomized studies, comparison of efficacy and identification of risk factors is limited. This is the main reason why the European Society of Biomodulation and Chemotherapy (ESBiC) is conducting a surveillance study that concentrates more on the evaluation of risk factors than on the therapeutic outcome of prospective randomized antimicrobial regimens: European Surveillance of Infections in Cancer Patients (ESIC). The present contribution is to determine which cancer patients are at low risk for fever, and can benefit from first-line treatment with treatment options such as monotherapy as well as on an outpatient basis.

Anti-Bacterial Agents↗

PubMedDate not supplied

Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human monoclonal antibody SC-1: first clinical and histopathological results.

In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In seven cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in five patients a significant regression of tumor mass could be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients.

Adenocarcinoma↗