Clinical Chemistry (clinical + chemistry)

Distribution by Scientific Domains

Selected Abstracts

Reference values for clinical chemistry tests during normal pregnancy

A Larsson
Objective, Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. Design, Longitudinal study of laboratory markers in normal pregnancies. Setting, Uppsala University Hospital, Sweden. Population, Healthy pregnant females. Methods, We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7,17; week 17,24; week 24, 28; week 28,31; week 31,34; week 34,38; predelivery (0,2 weeks before delivery) and postpartum (>6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Results, Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, ,-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. Conclusions, Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy. [source]

Biochemical and white blood cell profiles of baboon neonates consuming formulas with moderate and high dietary long-chain polyunsaturated fatty acids

A.T. Hsieh
Abstract Background, Clinical chemistry and complete blood count (CBC) values were determined in 14 term baboons (Papio species) consuming formula with moderate or high levels of dietary long-chain polyunsaturated fatty acids (LCPUFA) from 2,12 weeks of age. Method, Neonates were randomized to three groups: C: Control, no LCPUFA; L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); L3:1.00% DHA/0.67% ARA (w/w). Blood chemistries were assessed at 6 and 12 weeks and CBC parameters were measured at 2, 4, 8, 10, 12 weeks of age. Results, Dietary LCPUFA had significant effects on serum triglyceride (C > L,L3) and calcium (L > C,L3). No other significant effects of diet were detected; pooled values are presented for all other parameters. Conclusion, These data provide longitudinal biochemical and white cell/platelet/immunological data on LCPUFA-fed baboons over the first 12 weeks of life. Data ranges are similar to reference data in cases for which values exist and hematological changes reflect trends observed during human neonatal development. [source]

Uterine torsion diagnosed in a mare at 515 days' gestation

C. López
Summary A pregnant mare with a history of prolonged gestation (,515 days) and suspected diagnosis of fetal mummification was examined. Rectal palpation revealed that the left broad ligament of the uterus was dorsal and medial to the right uterine ligament and it was not possible to observe the cervix during vaginal examination. Transabdominal ultrasound revealed fluid in the uterus, fetal membranes and the uterine walls defined and thickened. Free fluid was not seen in the peritoneal cavity. Laboratory tests (blood cell count and clinical chemistry) were normal. Based on clinical history, physical examination and ultrasound findings, a chronic uterine torsion with fetal death was diagnosed and the mare was subjected to exploratory celiotomy. The uterus was strongly adhered to the peritoneum of the ventral abdominal wall and there were multiple adhesions to the colon. Hysterotomy was performed to remove the fetus and to permit repositioning of the uterus. When the fetus was removed, a large devitalised grey tissue area of the right ventral uterine horn was observed. Multiple adhesions prevented a rescue hysterectomy and euthanasia of the patient was performed. During the necropsy, a 180° cranial cervix clockwise uterine torsion was observed. This rare case of uterine torsion appears to be the most chronic case reported in the equine literature. [source]

Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction

Hayet Aberkane
Abstract: Gamma-glutamyltranspeptidase (GGT) is a well known cell plasma membrane and serum circulating enzyme. In clinical chemistry, GGT is used as a marker of alcohol consumption and drug uptake. Serum GGT activity varies in hepatobiliary diseases and cancer. This enzyme is involved in glutathione (GSH) metabolism, which is generally associated with antioxidant properties. However, in recent years, findings from our group and from others showed that GGT-catalysed extracellular metabolism of GSH leads, in the presence of iron, to the generation of reactive oxygen species (ROS). It was demonstrated that those highly reactive species oxidise lipids, cell surface protein thiols or activate transcriptional factors such as Nuclear Factor ,B (NF,B). The objective of the present work is to determine whether the red blood cells are targets for plasma GGT-initiated pro-oxidant reaction. The results obtained demonstrate that the GGT/GSH/iron system oxidises isolated erythrocyte membranes. A significant release of haemoglobin and a decrease of erythrocyte deformability are also observed. In addition, in vivo studies showed a relationship between plasma GGT activity and erythrocyte deformability in 20 studied subjects. In conclusion, GGT-mediated ROS production is able to oxidise erythrocytes and thus disturbs their functions. [source]

Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot study

Dr. Bruce E. Sands
Abstract We report the experience of 11 patients (of 60 planned patients) enrolled in a double-blind, placebo-controlled clinical trial of infliximab in patients with severe, active steroid-refractory ulcerative colitis. The study was terminated prematurely because of slow enrollment. Patients having active disease for at least 2 weeks and receiving at least 5 days of intravenous corticosteroids were eligible to receive a single intravenous infusion of infliximab at 5, 10, or 20 mg/kg body weight. The primary endpoint used in this study was treatment failure at 2 weeks after infusion. Treatment failure was defined as 1) unachieved clinical response as defined by a modified Truelove and Witts severity score, 2) increase in corticosteroid dosage, 3) addition of immunosuppressants, 4) colectomy, or 5) death. Safety evaluations included physical examination, clinical chemistry and hematology laboratory tests, and occurrence of adverse experiences. Four of 8 patients (50%) who received infliximab were considered treatment successes at 2 weeks, compared with none of 3 patients who received placebo. Improvement in erythrocyte sedimentation rates and serum concentrations of C-reactive protein and interleukin-6 correlated with the clinical response observed in patients receiving infliximab. Infusion with infliximab produced no significant adverse events. Infliximab was well tolerated and may provide clinical benefit for some patients with steroid-refractory ulcerative colitis. [source]

Tissue histopathology, clinical chemistry and behaviour of adult comt -gene-disrupted mice

Kristiina Haasio
Abstract Catechol- O -methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O -methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt -gene-disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen-dependent organs such as mammary glands and uterus. The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7,9% lower than that of the other groups. This was re,ected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal ,ndings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not re,ected as histopathological ,ndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice. The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Chronic toxicity/oncogenicity study of styrene in cd-1 mice by inhalation exposure for 104 weeks

George Cruzan
Abstract Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Mass spectrometry in newborn and metabolic screening: historical perspective and future directions

Donald H. Chace
Abstract The growth of mass spectrometry (MS) in clinical chemistry has primarily occurred in two areas: the traditional clinical chemistry areas of toxicology and therapeutic drug monitoring and more recent, human genetics and metabolism, specifically inherited disorders of intermediary metabolism and newborn screening. Capillary gas chromatography and electrospray tandem MS are the two most common applications used to detect metabolic disease in screening, diagnostics and disease monitoring of treated patients. A few drops of blood from several million newborn infants are screened annually throughout the world making this the largest application of MS in medicine. Understanding the technique, how it grew from a few dozen samples per week in the early 1990s to increasing daily volume today will provide important information for new tests that either expand newborn screening or screening in other areas of metabolism and endocrinology. There are numerous challenges to the further expansion of MS in clinical chemistry but also many new opportunities in closely related applications. The model of newborn screening and MS in medicine may be useful in developing other applications that go beyond newborns and inherited metabolic disease. As MS continues to expand in clinical chemistry, it is clear that two features will drive its success. These features are excellent selectivity and multiple analyte or profile analysis; features recognized in the 1950s and remain true today. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Immunophenotyping of peripheral blood, ranges of serum chemistries and clinical hematology values of healthy chimpanzees (Pan troglodytes)

G.A. Stone
This paper presents clinical chemistry, hematology and immunophenotyping data from 102 chimpanzees over a 2-year period. The groupings were: 3 years or less, 4,7 years, and 8+ years. These data are intended to augment formerly published information on these parameters and to serve as a concise reference guide for primate veterinarians and researchers for whom these data may be useful. This study has larger samplings than previously published data and more panel constituents by immunophenotyping. [source]

Oxygen infusions (hemoglobin-vesicles and albumin-hemes) based on nano-molecular sciences,

Professor Eishun Tsuchida
Abstract Since the discovery of a red-colored saline solution of a heme derivative that reversibly binds and releases oxygen (1983), significant efforts have been made to realize an oxygen infusion as a red cell substitute based on the sciences of both molecular assembling phenomena and macromolecular metal complexes. The authors have specified that hemoglobin (Hb)-vesicles (HbV) and recombinant human serum albumin-hemes (rHSA-heme) would be the best systems that meet the clinical requirements. (A) Hb is rigorously purified from outdated, donated red cells via pasteurization and ultrafiltration, to completely remove blood type antigen and pathogen. The HbV encapsulates thus purified concentrated Hb solution with a phospholipid bimolecular membrane (diameter, 250,nm,), and its solution properties can be adjusted comparable with blood. Surface modification of HbV with a water-soluble polymer ensures stable dispersion state and storage over a year at 20°C. In vivo tests have clarified the efficacy for extreme hemodilution and resuscitation from hemorrhagic shock, and safety in terms of biodistribution, metabolism in reticuloendothelial system (RES), clinical chemistry, blood coagulation, etc. The HbV does not induce vasoconstriction thus maintains blood flow and tissue oxygenation. (B) rHSA is now manufactured in Japan as a plasma-expander. The rHSA can incorporate eight heme derivatives (axial base substituted hemes) as oxygen binding sites, and the resulting rHSA-heme is a totally synthetic O2 -carrier. Hb binds endothelium-derived relaxation factor, NO, and induces vasoconstriction. The rHSA-heme binds NO as Hb does, however, it does not induce vasoconstriction due to its low pI (4.8) and the resulting low permeability across the vascular wall (1/100 of Hb). A 5%-albumin solution possesses a physiologic oncotic pressure. Therefore, to increase the O2 -transporting capacity, albumin dimer is effective. Albumin dimer can incorporate totally 16 hemes with a regulated oncotic pressure. The rHSA-heme is effective not only as a red cell substitute but also for oxygen therapeutics (e.g. oxygenation for tumor). Significant efforts have been made to produce HbV and rHSA-heme with a facility of Good Manufacturing Practice (GMP) standard, and to start preclinical and finally clinical trials. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Body fluid proteomics: Prospects for biomarker discovery

Sung-Min Ahn
Abstract Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles , the so-called "signatures of disease" , using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000,1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine. [source]

Precursor ion scan profiles of acylcarnitines by atmospheric pressure thermal desorption chemical ionization tandem mass spectrometry

Giuseppe Paglia
The fatty acyl esters of L-carnitine (acylcarnitines) are useful biomarkers for the diagnosis of some inborn errors of metabolism analyzed by liquid chromatography/tandem mass spectrometry. In this study the acylcarnitines were analyzed by atmospheric pressure thermal desorption chemical ionization using a commercial tandem mass spectrometer (APTDCI-MS/MS). The method is based on the precursor ion scan mode determination of underivatized acylcarnitines desorbed from samples by a hot desolvation gas flow and ionized by a corona pin discharge. During desorption/ionization step the temperature induces the degradation of acylcarnitines; nevertheless, the common fragment to all acylcarnitines [MH,59]+ is useful for analyzing their profile. APTDCI parameters, including angle of collection and incidence, gas flows and temperatures, were optimized for acylcarnitines. The experiments were performed drying 2,µL of an equimolar mixture of acylcarnitine standards on a glass slide. The specificity was evaluated by comparing product ion spectra and the precursor ion spectra of 85 m/z of acylcarnitines obtained by the APTDCI method and by electrospray ionization flow injection analysis (ESI-FIA). The method was also employed to analyze acylcarnitines extracted from a pathological dried blood spot and a control. The method enables analysis of biological samples and recognition of some acylcarnitines that are diagnostic markers of inherited metabolic diseases. The intrinsic high-throughput analysis of the ambient desorption ionization methods offers a new opportunity either for its potential application in clinical chemistry and for the expanded screening of some inborn errors of metabolism. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Effects of aging on hematology and serum clinical chemistry in chimpanzees (Pan troglodytes)

Elaine N. Videan
Abstract A number of age-related changes in physiological functions have been identified in macaques and humans. However, few studies have examined physiological aging in chimpanzees, despite the increasing age of the chimpanzee population. We documented age-related changes in seven hematology and 17 clinical chemistry parameters in 49 adult chimpanzees (17 males, 32 females) as a comparative viewpoint with human and macaque aging. Longitudinal data were analyzed using weighted linear and quadratic mixed effects regression models. Male chimpanzees exhibited a significant age-related increase in anemia risk, based on significant decreases in hemoglobin (F1,49=12.45, P=0.0009) and hematocrit (F1,49=15.42, P=0.0003). Both sexes exhibited significant age-related decreases in both kidney and liver function. Decreases in kidney function were noted by significant increases in blood urea nitrogen (F1,45=3.92, P=0.036) and creatinine (F1,50=5.63, P=0.022) as well as changes in electrolyte (i.e., sodium, potassium, phosphorous, chloride) balance. Declining liver function was based on significant increases in globulin (F1,46=32.34, P<0.0001) and decreases in albumin (F1,48=23.42, P<0.0001). These changes were most evident beginning at 25,30 years of age in males and 30,35 years of age in females. We recommend amending chimpanzee age classes to categorize males over 25 years and females over 30 years as aged. Am. J. Primatol. 70:327,338, 2008. © 2007 Wiley-Liss, Inc. [source]

Phase 1 Dose-Escalation Study of CP-690 550 in Stable Renal Allograft Recipients: Preliminary Findings of Safety, Tolerability, Effects on Lymphocyte Subsets and Pharmacokinetics

E. Van Gurp
CP-690 550 inhibits Janus kinase 3 with nanomolar potency. In this dose-escalation study, we assessed the safety, tolerability, effects on lymphocyte subsets, and pharmacokinetics of CP-690 550 when coadministered with mycophenolate mofetil in stable renal allograft recipients for 28 days. Twenty-eight patients were enrolled. Six patients received CP-690 550 5 mg twice daily (BID), 6 patients received 15 mg BID, 10 patients received 30 mg BID, and 6 patients received placebo. The most frequent adverse events were infections and gastrointestinal (abdominal pain, diarrhea, dyspepsia, and vomiting). CP-690 550 15 mg BID and 30 mg BID were associated with a mean decrease in hemoglobin from baseline of 11% and a mean decrease in absolute natural killer cell counts of 50%. CP-690 550 30 mg BID was also associated with a mean increase in absolute CD19+ B-lymphocytes of 130%. There were no changes in the number of neutrophils, total lymphocytes, platelets, or CD4+ or CD8+ T cells; clinical chemistry; vital signs; or electrocardiograms from the pretreatment baseline. Administration of CP-690 550 without a concomitant calcineurin inhibitor resulted in CP-690 550 exposures consistent with previous studies in nontransplant subjects. Additional dose-ranging studies are warranted to evaluate the safety and efficacy of CP-690 550 in renal transplant recipients over longer treatment duration. [source]

Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle Dogs

Maria V. Papadopoulou
The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source]

Clinical Pathology Alterations in Pregnant and Non-Pregnant Rats following Scorpion Envenomation

Hmed Ben Nasr
Existing diagnostic criteria are not sufficiently specific to allow antivenin administration in the absence of a confirmed scorpion sting. This study was performed to evaluate conventional haematological and serum chemical measurements as potential indices of scorpion envenomation. Adult, cycling nulliparous and near-term primiparous, white Wistar rats received a single subcutaneous injection of crude venom (600 µg/kg) from the Buthidae scorpion (Buthus occitanus tunetanus). All envenomed rats were observed for external signs and symptoms of toxicity until necropsy, which entailed terminal blood collection at either 0.5, 1, 2, or 4 hr after venom administration (n = 6 per reproductive state per time-point) for evaluation of selected clinical chemistry and haematological analytes. Control cohorts (matched for age and reproductive state) received saline injections subcutaneously and were necropsied at 0.5 hr. Almost all envenomed rats but no control animals displayed physical symptoms of intoxication, including agitation, mastication with hypersalivation, and/or vocalizing. Reproducible alterations in clinical pathology parameters were lacking in venom-treated rats regardless of reproductive status, although modest but significant Rho correlations suggested that mild haemoconcentration, haemolysis, renal function deficits and possibly coagulation difficulties developed over time. [source]