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Effect of corticosteroids on diaphragm function and biochemistry in the rabbit.

The effects of corticosteroid administration for 2 weeks on diaphragm histology, biochemistry, and function were assessed in the rabbit at rest and during inspiratory loading to respiratory failure, and compared to the extensor digitorum longus and untreated control animals. There were marked pathologic changes in the diaphragm after corticosteroid administration and significant alterations in diaphragm glycogen level (118.7 +/- 2.8 versus 56.2 +/- 1.0 mmol/kg wet weight, p less than 0.01) and lactate level (5.3 +/- 0.3 versus 3.5 +/- 0.4 mmol/kg wet weight, p less than 0.01) with only minimal changes in the skeletal muscle. Although respiratory muscle endurance in the control group increased from 142 +/- 17 min at baseline to 155 +/- 20 at Week 1 and 183 +/- 13 at Week 2 (p less than 0.05), it fell progressively from 135 +/- 19 min at baseline to 99 +/- 5 at Week 1 and 88 +/- 9 at Week 2 (p less than 0.01) in the corticosteroid-treated animals. On the other hand, there was no significant change in resting Pdimax after corticosteroid administration. In addition, there was no significant change in Pdimax, Pdi/Edi ratio, or glycogen level at the point of respiratory failure, but diaphragm lactate levels were increased (8.5 +/- 0.8 versus 5.3 +/- 0.3, p less than 0.05). When variable degrees of diaphragm dysfunction were induced by phrenic nerve pacing and/or thoracoabdominal binding, the degree of biochemical change associated with diaphragm dysfunction was significantly greater in corticosteroid-treated animals. We conclude that corticosteroid administration in the rabbit alters diaphragm histopathology and biochemistry as well as respiratory muscle endurance, but not strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical biochemistry service for liver transplantation.

The first significant successes with human liver transplantation took place only in 1968, but the future for this new surgical procedure now seems assured. Its success is heavily dependent upon the provision of pathology services, in particular from clinical biochemistry. The experiences with some of the 39 British liver transplants carried out so far are recorded. At operation, a minimum of 20 technician-hours, usually outside normal working hours, is called for. In the immediate post-operative period, intensive biochemical monitoring is essential. Once the major homeostatic mechanisms are re-established after surgery, the principal biochemical investigations are those of organ function. While no specific test for rejection is yet available, the diagnosis of rejection can be made from results of the routine pathology investigations. The role of the clinical biochemistry laboratory in the management of these patients is to provide reliable results seven days a week on a range of tests. The clinical biochemist is also well placed to contribute to the solution of some of the outstanding problems of organ transplantation.

Blood Glucose↗

Assessment of the feasibility of conducting population prevalence studies of chronic renal failure according to ethnic group: a survey of clinical biochemistry laboratories in Greater London and south east England.

The planning of renal replacement therapy is based on assessment of population need for the white population, but uses historical trends in treatment uptake for black and Asian ethnic minority groups, for whom the incidence of chronic renal failure (CRF) is not known. Epidemiological studies of CRF are based upon follow-up of plasma creatinine results obtained from clinical biochemistry laboratories. We conducted a postal questionnaire survey of UK National Health Service (NHS) and private clinical biochemistry laboratories in Greater London and the south east of England to arrange the design and test the feasibility of carrying out a study to determine ethnic-specific rates of CRF. Fifty-five NHS laboratories (90%) and 19 private laboratories (57%) responded. Few pathology computer systems recorded ethnic group, patient post code, or diagnosis; although 31 of the laboratory computers (42%) were linked with the hospital Patient Administration System which could supply these data. Approximately 5.5 million electrolyte profiles and 20 million individual renal function tests are carried out annually in south east England. Ninety per cent of those were performed within NHS laboratories, implying that a study can use NHS sources alone without risk of any undue bias. Sixty laboratories (81%) included creatinine in their routine electrolyte profile, which would be a requirement for any study. Thirty-one laboratories (42%) archived tests within 1 year of entry, which would rule out a retrospective study design. A prospective study is feasible and should be carried out as soon as is practicable.

Clinical Laboratory Information Systems↗

Experience with assessing the quality of comments on clinical biochemistry reports.

We assess a previously described scoring system for the appropriateness of interpretative comments on clinical biochemistry reports over 21 distributed cases and over a group of 41 UK-based participants. The distributed cases covered a range of clinical scenarios and included pre- and post-analytical problems. The UK-based participants had all registered an interest in using this case participation for their continuing professional development; all had higher professional qualifications in clinical biochemistry, and the group included participants based in teaching hospitals and district general hospitals as well as those with a medical or a scientific background. Although the present scoring system favours participants who mention more than one possible outcome and who include several ideas for further investigation, its advantages seem to outweigh its disadvantages. The scored cases are currently unique, and are seen to be of major educational value not only by active participants but also by those who are using them for teaching or in discussion groups.

Chemistry, Clinical↗

Is leptin associated with serum lipid profile or any other parameters of blood biochemistry in post-menopausal women with osteoporosis?

We investigated the relationship between serum leptin concentration, serum lipid profile and other blood biochemistry parameters in healthy post-menopausal women. Blood samples for analysis of serum leptin concentration, blood biochemistry and hormonal status, and urine samples for calcium measurement were taken from 122 women. No significant correlation was found between serum leptin concentration and serum lipid profile. The concentration of serum leptin was significantly associated with body mass index (BMI), luteinizing hormone (LH) and alanine transaminase (ALT). BMI was found to be a statistically significant independent factor for serum leptin concentration. We conclude that leptin was not associated with serum lipids and lipoproteins in post-menopausal women. Leptin was associated with BMI, ALT and LH, however, with BMI being an independent predictor of leptin concentration. There was a relationship between LH and serum leptin concentration even after menopause, and ALT correlated with serum leptin concentration through BMI.

Adult↗

Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?

OBJECTIVE: To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits. BACKGROUND: WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. METHODS: We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS. RESULTS: WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time. CONCLUSIONS: The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Adenosine Triphosphate↗

Muscle biochemistry and the ontogeny of flight capacity during behavioral development in the honey bee, Apis mellifera.

A fundamental issue in physiology and behavior is underlie major behavioral shifts in organisms as they transitions are common in nature and include the age-related switch from nest/hive work to foraging in social insects such as honey bees (understanding the functional and genetic mechanisms that adopt new environments or life history tactics. Such). Because of their experimental Apis mellifera tractability, recently sequenced genome and well understood biology, honey bees are an ideal model system for integrating molecular, genetic, physiological and sociobiological perspectives to advance understanding of behavioral and life history transitions. When honey bees (Apis mellifera) transition from hive work to foraging, their flight muscles undergo changes Apis mellifera that allow these insects to attain the highest rates of flight muscle metabolism and power output ever recorded in the animal kingdom. Here, we review research to date showing that honey bee flight muscles undergo significant changes in biochemistry and gene expression and that these changes accompany a significant increase in the capacity to generate metabolic and aerodynamic power during flight. It is likely that changes in muscle gene expression, biochemistry, metabolism and functional capacity may be driven primarily by behavior as opposed to age, as is the case for changes in honey bee brains.

Age Factors↗

Effect of maternal hypothyroxinaemia in the rat on brain biochemistry in adult progeny.

The effects of maternal hypothyroxinaemia during pregnancy on subsequent brain biochemistry in progeny was studied. Normal and partially thyroidectomized rat dams were mated and progeny allowed to grow to adulthood. Brain regions (cerebellum, medulla, midbrain, cerebral cortex and paleocortex) were dissected out and the activities of various cell marker enzymes were determined, along with cholesterol contents. Maternal hypothyroxinaemia was without effect on body weight, brain weight or thyroid status of adult progeny. Oligodendroglial marker enzyme activities were altered in progeny from thyroidectomized dams. 2',3'-Cyclic nucleotide 3'-phosphohydrolase was decreased in the medulla (by 37%) and midbrain (by 32%). 5'-Nucleotidase was also diminished in the same brain regions, by 33% in the medulla and by 35% in the midbrain. In contrast, oleate esterase was increased (by 39%) in the paleocortex. Although these enzymes are putatively involved in myelin metabolism, no changes were observed in the concentration of a major myelin lipid (cholesterol). The activity of beta-D-glucuronidase (a general neuronal marker) was decreased (by 30%) in the paleocortex, whereas N-acetyl-beta-D-galactosaminidase (a general glial marker) was unchanged in all brain regions. In summary, maternal hypothyroxinaemia has irreversible effects on brain biochemistry in adult progeny. The damage is parameter-selective and brain region-specific, analogous to the pattern of neurological damage seen in offspring born to hypothyroxinaemic women in iodine-deficient endemias.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Characterization of a Novel BTD Hypomorphic Variant in a Patient with Complex Neurodevelopmental Delay: Resolving Actionable Metabolic Vulnerabilities Beyond Borderline Plasma Biochemistry.

Plasma biochemistry often presents significant limitations in diagnosing borderline metabolic disorders, particularly within complex neurodevelopmental phenotypes. Here, we present the clinical genomic evaluation of a six-year patient presenting with early-onset hypotonia and severe gastrointestinal complications whose newborn screening panel did not evaluate biotinidase (BTD) activity. While initial baseline plasma biochemistry yielded borderline residual BTD function (46% of the population mean), targeted sequencing identified a novel, compound heterozygous hypomorphic variant (p.Thr459Met) in trans with the common p.Asp424His allele. In vitro functional validation confirmed that p.Thr459Met induces severe protein misfolding and intracellular retention, impairing enzyme secretion. Biotin supplementation triggered a documented and favorable therapeutic improvement, establishing this borderline enzymatic background as an actionable metabolic vulnerability unmasked by chronic gastrointestinal stressors. This study underscores the critical value of functional genomic characterization over static enzymatic biomarkers to identify highly treatable metabolic components within heterogeneous clinical landscapes.

Humans↗

UCLA conference. Biochemistry of collagen in diseases.

Collagen, the major extracellular matrix component, comprises a family of closely related, yet genetically distinct proteins that provide physiologic tensile properties to the tissues. The recent progress made in understanding the normal biochemistry and biology of collagens has permitted us to identify different levels at which errors might be introduced into the structure and metabolism of this protein. Several acquired and heritable diseases are now known to involve distinct abnormalities in collagen. This conference reviews some of the latest discoveries in the biochemistry of collagen and highlights some disease entities in which definitive information on molecular alterations in collagen is available.

Collagen↗

Hematology and plasma biochemistry reference range values for free-ranging desert tortoises in Arizona.

Baseline values and ranges for 10 hematologic and 32 plasma chemistry parameters were analyzed for 36 free-ranging Sonoran desert tortoises (Gopherus agassizzi) collected in Yavapai and La Paz Counties (Arizona, USA) from 1990 to 1995. Tortoises were radio tagged from 1990 to 1994, and attempts were made to recapture them three times a year. Tortoises were weighed, measured, and chemically immobilized to collect blood for hematology and blood chemistry assessments. Tortoise biochemistry differed (P < 0.01) between sites and sexes and among seasons and years. Normal reference ranges for hematologic and plasma biochemistry parameters were determined. Seasonal and annual differences in hematology and blood chemistry were related to rainfall patterns, forage availability, and physiological condition.

Animal Feed↗

Hematologic, protein electrophoresis, biochemistry, and cholinesterase values of free-living black stork nestlings (Ciconia nigra).

Hematologic, protein electrophoresis, serum biochemistry, and cholinesterase values were determined in 36 free-living black stork nestlings (Ciconia nigra) between 25 and 53 days of age in order to establish normal reference values for this population. The following values were evaluated: white blood cell counts, red blood cell counts, packed cell volume, hemoglobin, heterophils, lymphocytes, monocytes, eosinophils, prealbumin, albumin, alpha-globulin, beta-globulin, gamma-globulin, total protein, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, calcium, phosphorus, iron, cholesterol, glucose, triglycerides, uric acid, urea, creatinine, total solids, bile acids, and butyrylcholinesterase. Sex-dependent differences were observed in hemoglobin, prealbumin, albumin, gamma-globulin, total protein, alkaline phosphatase, and triglycerides. Packed cell volume, butyrylcholinesterase, aspartate aminotransferase, creatine kinase, and creatinine increased with age, whereas albumin, mean cell volume, calcium, phosphorus, cholesterol, and total solids decreased with age. These hematologic and serum biochemistry values can be used as reference ranges in free-living black stork nestlings.

Albumins↗

The biochemistry of Dupuytren's disease.

The molecular biochemical aspects of Dupuytren's disease have been studied for decades. This article summarizes biochemical influences on myofibroblast contractility, endogenous and exogenous chemical regulation, the influence of growth factors, and the biochemistry of collagen. A clear insight into the biochemistry of Dupuytren's disease may provide a foundation for future clinical interventions.

Collagen↗

[Blood protein technological industrial developments as a mirror of fundamental studies bgy the Institute of Biochemistry of the Ukrainian National Academy of Sciences].

We have examined the technology for an industrial chromatographic production highly purified factor VIII concentrate intended for therapy of the hemophilia A and characterized this factor VIII. The final product has been prepared from cryoprecipitate of pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on AEM and CEM ion exchange and SPG or SHR gel filtration chromatography. The specific activity of the product was 459 +/- 19 IU factor VIII/mg protein (n = 10), corresponding to a purification factor of about 15,000. The concentrate was free of the fibrinogen, alpha-2-macroglobulin, alpha-1-acidglycoprotein, haptoglobin. Only three contaminants could be detected: fibronectin, immunoglobulins A and G (about 0.020, 0.004 and 0.034 microgram/IU factor VIII, respectively). The purity of the final product was confirmed by SDS polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar-Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Another examination was concern to the technology for an industrial chromatographic production highly purified factor IX concentrate intended for therapy of the hemophilia B and characterized this factor IX. The final product has been prepared from pooled human plasma using a large-scale procedure combining four conventional chromatographic steps based on AEM ion exchange, AFM affinity and SGS gel filtration chromatography. The specific activity of the product was 149 +/- 10 IU factor IX/mg protein (n = 10), corresponding to a purification factor of about 9000. The concentrate was free of the vitamin K-dependent clotting factors II, VII and X and of proteins C and S. Most of possible contaminants were absent in this new product. High-molecular-weight kininogen, factor VIII, XI, XII or prekallikrein were not detected. There were no activated factors, such as factors IXa and Xa, no thrombin and no phospholipids. Only two contaminants could be detected: C4 and inter-alpha-trypsin inhibitor (about 0.8 and 1.2 mg/IU factor IX, respectively). The purity of the final product was confirmed by SDS polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar-Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Thrombogenicity tests in rabbits revealed that the high purified factor IX by Institute of Biochemistry technology tested had a lower thrombogenic power than the commercial factors IX tested. The concentrate has been subjected to a special solvent--detergent treatment for definite time and temperature during its production to virus inactivation (it will be describe in following special examination). These data demonstrate that a highly purified therapeutic clotting factor VIII and IX concentrates can be prepared from human plasma by conventional chromatographic methods developed by Institute of Biochemistry of NAS of Ukraine and Combio Ltd.

Academies and Institutes↗

[Basic directions of research of the department of lipid biochemistry].

The review deals with the scientific activity of the Department of Biochemistry of Lipids of the Palladin Biochemistry Institute of the National Academy of Sciences of Ukraine. The estimation of the functional role of some major lipids and of the minor lipid components, namely, N-acylethanolamines (NAE), is the main problem of the scientific investigations of the Department. The role of some lipids in the pathogenesis of diseases accompanied by the oxidative stress was also studied. The Department was the first to find and identify NAE in neuroblastoma C1300 N18 cells. It was shown that NAE with long saturated acyl chains inhibited veratridine-activated fast sodium channels. NAE also activated uterine plasma membrane smooth muscle Ca2+, Mg(2+)-ATPase, and inhibited Fe(2+)-induced free radical oxidation in mitochondria. The results of these investigations served as a basis for development of pharmacological substances with membrane protective properties. It was shown that, at different diseases accompanied by the oxidative stress, a significant change in the lipid composition of cell membranes occurred. Sometimes these changes were adaptive in character, which favored the cell viability adaptation to pathological conditions. The new level of regulation of adaptive reactions can be accompanied by the development of additive injuries of cell viability, which may be caused by the altered level of biologically active cell lipid components. Based on the results of these investigations, the preparation intended for treatment of male infertility was developed. The pharmacological substances intended for treatment of morphine abuse and acute ischemia of myocardium were created.

Humans↗

Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study.

Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

Adult↗

Preanalytical phase of sport biochemistry and haematology.

Biochemistry and haematology are more and more important and sometimes crucial in sport medicine for diagnosing, controlling and preventing purposes. The analytical process and the global laboratory quality are heavily influenced by the preanalytical phase, including biological material collection, identification, storage and transport of the specimen, preparation for analyses of the specimen through centrifugation, freezing and thawing, aliquoting and sampling. The increasing interest of sport biochemistry should be linked to a knowledge of principal problems and pitfalls in the preanalytical phase of various parameters, commonly used in following training, diet, and performances of athletes, to avoid misinterpretation of data and to improve usefulness of biochemical investigations. We prepared a practical review of preanalytical aspects of principal analyses applied to the athletes. We include the choice of anticoagulant and its limits for haematological tests, the preparation and manipulation of specimens for hormonological investigation, especially for labile molecules, and for cardiac markers, lactate, cytokines, micronutrients, antioxidant molecules. Preanalytical phase of specimens different from blood are also showed, including urine and saliva, and some aspects of preparation of materials to be analyzed with molecular biology technology are treated. Stability of some analytes, when the parameter is fundamental for the clinical usefulness of the results, is supplied. Preparation of the subjects, however, including the possible influence of physical exercise and biological rhythms on the biochemical and haematological parameters, are not listed.

Chemistry, Clinical↗

Community-based survey on blood pressure, blood biochemistry and dietary habits in Pu-Li, Taiwan.

The target population of this study were all residents over the age of 30 in Pu-Li. Stratified cluster sampling was employed. Household visits were carried out in 1987 by the Yang-Ming Crusade, organized by well-trained medical students of the National Yang-Ming Medical College. A total of 1,738 persons out of a potential 2,573 eligible subjects were contacted by at least one of the two interviews or a blood draw. The crude and adjusted (for vacant households) rates were 68% and 84% respectively. Age, sex, and education were evenly distributed. The distribution of physiological variables and blood biochemistry were as follows: 23.0 +/- 3.2 for body mass index (BMI = kg/m2; men 22.8 +/- 3.0, women 23.2 +/- 3.3), 129.7 +/- 20.7 mmHg for systolic blood pressure (men 130.4 +/- 19.6 mmHg, women 128.9 +/- 21.8 mmHg), 81.9 +/- 12.9 mmHg for diastolic blood pressure (men 82.9 +/- 12.8 mmHg, women 80.9 +/- 12.9 mmHg), 103.6 +/- 29.6 mg/dl for fasting plasma glucose (men 101.8 +/- 21.9 mg/dl, women 105.2 +/- 35.2 mg/dl), 222.1 +/- 57.2 mg/dl for cholesterol (men 221.9 +/- 56.5 mg/dl, women 222.3 +/- 57.9 mg/dl), 162.7 +/- 115.5 mg/dl for triglyceride (men 170.3 +/- 117.1 mg/dl, women 155.7 +/- 113.6 mg/dl), 5.8 +/- 3.0 mg/dl for uric acid (men 6.5 +/- 4.8 mg/dl, women 5.2 +/- 1.5 mg/dl). Blood pressure and blood biochemistry variables were positively associated with age. Comparatively, men had much more unhealthy life styles than women; due to prevalences for cigarette smoking (56.0% vs. 3.0%), alcohol intake (43.8% vs. 6.6%) and betel-nut chewing (18.2% vs. 0.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗