Search

Maternal anaemia in early pregnancy is associated with poor pregnancy outcomes. Furthermore, preconceptional health can influence the health during pregnancy. The aim of this study was to investigate which preconceptional factors were associated with haemoglobin (Hb) concentration in early pregnancy.In Tanzania, 226 women were followed at preconception and during early pregnancy. Red blood cell (RBC) morphology, serum micronutrient concentration, demographic characteristics and health status were assessed in preconception and in early pregnancy. The association between preconceptional factors and Hb concentration in early pregnancy was investigated using simple and multiple linear regression analyses stratified by preconceptional anaemia status.Mean Hb was 123 and 119 g/l before conception and during early pregnancy (median gestational age 53 days) respectively. Preconceptional mid-upper arm circumference (MUAC) (adjusted coefficient (AC) 0.35 95% CI 0.9-0.61) and preconceptional Hb concentration (AC 0.45 95% CI 0.36-0.54) were positively associated with early pregnancy Hb concentration, whereas preconceptional microcytic hypochromic RBC morphology (AC -6.00 95% CI -9.56 to -2.44) was negatively associated with early pregnancy Hb concentration. In addition, treatment of preconceptional malaria was positively associated with early pregnancy Hb concentration (AC 6.45 95% CI 0.74-12.2) among women with preconceptional anaemia. In contrast, among preconceptional non-anaemic women, only preconceptional Hb concentration and medium socio-economic status was positively associated with early pregnancy Hb concentration.Mid-upper arm circumference (MUAC) and Hb measurements in preconception can help to detect women at increased risk of low Hb concentration in early pregnancy.L'anémie maternelle en début de grossesse est associée à de mauvais résultats de grossesse. En outre, la santé préconceptionnelle peut influer sur la santé pendant la grossesse. Le but de cette étude était d'investiguer les facteurs préconceptionnels associés à la concentration d'hémoglobine (Hb) en début de grossesse. MÉTHODES: En Tanzanie, 226 femmes ont été suivies avant la conception et durant le début de la grossesse. La morphologie des globules rouges (GR), la concentration sérique en micronutriments, les caractéristiques démographiques et l’état de santé ont été évalués avant la conception et durant le début de la grossesse. L'association entre les facteurs préconceptionnels et la concentration d'Hb au début de la grossesse a été investiguée en utilisant des analyses de régression linéaire simples et multiples stratifiées selon le statut d'anémie préconceptionnelle. RÉSULTATS: Les concentrations moyennes d'Hb étaient respectivement de 123 g/L et de 119 g/L avant la conception et en début de grossesse (âge gestationnel médian: 53 jours). Le périmètre brachial (PB) préconceptionnel (coefficient ajusté (AC): 0.35; IC 95%: 0.9 à 0.61) et la concentration préconceptionnelle d'Hb (AC: 0.45; IC 95%: 0.36 à 0.54) étaient positivement associés à la concentration d'Hb au début de la grossesse, alors que la morphologie hypochrome microcytaire des GR préconceptionnelle (AC: −6.00; IC 95%: −9.56 à −2.44) était négativement associée à la concentration d'Hb en début de grossesse. De plus, le traitement du paludisme préconceptionnel était positivement associé à la concentration d'Hb au début de la grossesse (AC: 6.45; IC 95%: 0.74 à 12.2) chez les femmes souffrant d'anémie préconceptionnelle. En revanche, chez les femmes non anémiques en préconception, seule la concentration d'Hb préconceptionnelle et le statut socioéconomique moyen présentaient une association positive avec la concentration d'Hb en début de grossesse.Les mesures du PB et de la concentration d'Hb avant la conception peuvent aider à détecter les femmes à risque accru de faible concentration d’HB en début de grossesse.

Kingella kingae is a rarely isolated opportunistic pathogen in the family Neisseriaceae. Thirteen strains of this organism, including six strains isolated in Denmark, were characterized. They formed a homogeneous group of small, non-motile, fastidious Gram-negative rods which were beta-haemolytic, oxidase positive, catalase negative and saccharolytic. Acid was produced from glucose and maltose. Growth was most pronounced aerobically but corroding colonies increased considerably in size during anaerobic incubation.

Sixty-seven out of 88 Neisseria gonorrhoeae strains isolated from test-of-cure (TOC) specimens during a five-months' period were included in the study. For 62 patients sufficient information was obtained in order to distinguish between relapse (34 ptt) and re-infection (28 ptt). For comparison with strains from these two groups of patients, 63 urogenital and 21 pharyngeal gonococcal strains isolated during the same period of time were randomly selected. The distributions according to susceptibility to penicillin for TOC strains and control strains corresponded to those found for the total number of TOC strains (275) and other strains (3,345) tested in 1979, respectively. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent. The TOC strains did not differ from the control strains in sensitivity to the complement-dependent bactericidal activity of normal human serum. However, gonococcal strains less susceptible to penicillin in vitro (MIC values within the range 0.1-2.0 microgram/ml) were significantly more sensitive to the complement-dependent activity of normal human serum (P less than 0.01) than strains fully susceptible to penicillin (MIC less than 0.01 microgram/ml.) Penicillin-resistant strains (MIC greater than 2.0 microgram/ml) did not differ from strains susceptible to less than 0.1 microgram penicillin/ml and were slightly more serum-resistant than the less susceptible strains (P less than 0.05). No difference in serum-sensitivity of urogenital and pharyngeal isolates could be demonstrated. The level of bactericidal activity of homologous convalescent serum was unrelated to the presence of antibodies either to gonococcal pili or crude gonococcal antigen preparations. The sensitivity to normal human serum of a certain strain was not correlated with sensitivity to homologous convalescent serum.

In order to characterize serum-resistant and serum-sensitive strains of N. gonorrhoeae, the protein I serotype, auxotype, and penicillin susceptibility of 128 strains were tested. Sensitivity to the complement-dependent bactericidal activity of normal human serum was highly associated with protein I serotype (p less than 0.001). Thus 85% of serotype 1-3 strains were serum-resistant, whereas 86% of serotype 8 strains and all strains with serotypes 8 + 9 or 9 were serum-sensitive. Serum-resistance or sensitivity for a given serotype was independent of auxotype. The susceptibility to penicillin within the serotypes 1-3 was significantly associated with auxotype (p = 0.0016); all AHU- (requirement for arginine, hypoxanthine and uracil) strains had MICs of penicillin of 0.04 microgram/ml or less and were serotypes 1-3. Among the non-AHU-strains, serotype 9 was significantly more penicillin susceptible than the other serotypes (p less than 0.003).

A plaque assay for determination of the sensitivity of Neisseria gonorrhoeae to the complement-dependent bactericidal activity of normal human serum was evaluated. The method was found to be rapid and easy to perform. All strains, which gave a positive result by the plaque assay, were serum-sensitive in a quantitative assay, whereas only 78% of strains giving negative results by the plaque assay were true serum-resistant. The growth of a few gonococcal strains was inhibited, i.e. formed plaques, after exposure to genuine as well as to heat-inactivated normal human serum.

OBJECTIVE: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.DESIGN: Retrospective register-based cohort study using nationwide registers from 1998 to 2012.SETTING: The North Denmark Region.PARTICIPANTS: In total, 638 352 individuals were included.PRIMARY AND SECONDARY OUTCOME MEASURES: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models.RESULTS: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14).CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.

The plasma proteinase inter-alpha-trypsin inhibitor is necessary for normal expansion of the cumulus-oocyte complex (COC) and lack of inter-alpha-trypsin inhibitor results in severe infertility. After diffusion from the circulation into the follicles, inter-alpha-trypsin inhibitor is incorporated into the extracellular hyaluronan network of the expanding COC. However, mixing isolated inter-alpha-trypsin inhibitor with hyaluronan in vitro does not result in coupling to hyaluronan. Other components must be present. A recently developed electrophoretic technique by which hyaluronan-bound inter-alpha-trypsin inhibitor is immobilized was used to demonstrate coupling activity in human and bovine follicular fluid that is necessary for the formation of a firm binding between inter-alpha-trypsin inhibitor heavy chains and hyaluronan, as observed in vivo. No coupling activity could be detected in human serum. Coupling occurred only in the presence of follicular fluid. The coupling activity of follicular fluid was irreversibly destroyed by heat treatment, lowering of pH or tryptic digestion, indicating that the coupling activity is associated with a protein. Calcium ions are essential for the coupling reaction. The binding reaction in vitro using intact inter-alpha-trypsin inhibitor is slow and occurs over 24 h. The early-formed complexes between inter-alpha-trypsin inhibitor and hyaluronan contain small amounts of bikunin, whereas the end product contains heavy chains and essentially no bikunin. The heavy chains released from inter-alpha-trypsin inhibitor by NaOH treatment bound immediately to hyaluronan, indicating that the dissociation of heavy chains from inter-alpha-trypsin inhibitor is the rate-limiting step. In conclusion, at least four components are essential for the covalent binding of heavy chains to hyaluronan: inter-alpha-trypsin inhibitor and calcium from plasma, hyaluronan and one or more proteins found in follicular fluid.

A trypsin inhibitor from Ciona intestinalis, present throughout the animal, was purified by ion-exchange chromatography followed by four HPLC steps. By MS the molecular mass of the native form was determined to be 6675 Da. The N-terminal amino acid sequence was determined by protein sequencing, but appeared to be partial because the theoretical molecular mass of the protein was 1101 Da too low. Thermolysin treatment gave rise to several fragments each containing a single disulphide bridge. By sequence analysis and MS intramolecular disulphide bridges could unequivocally be assigned to connect the pairs Cys4-Cys37, Cys8-Cys30 and Cys16-Cys51. The structure of the inhibitor is homologous to Kazal-type trypsin inhibitors. The inhibitor constant, KI, for trypsin inhibition was 0.05 n m whereas chymotrypsin and elastase were not inhibited. To reveal the complete sequence the cDNA encoding the trypsin inhibitor was isolated. This cDNA of 454 bp predicts a protein of 82 amino acid residues including a 20 amino acid signal peptide. Moreover, the cDNA predicts a C-terminal extension of 11 amino acids compared to the part identified by protein sequencing. The molecular mass calculated for this predicted protein is in accordance with the measured value. This C-terminal sequence is unusual for Kazal-type trypsin inhibitors and has apparently been lost early in evolution. The high degree of conservation around the active site strongly supports the importance of the Kazal-type inhibitors.

The proteinase inhibitor inter-α trypsin inhibitor (ITI) is a blood-derived protein necessary for normal female fertility. Absence of ITI leads to ovulation of naked oocytes that cannot fertilise. ITI consists of two heavy chains (ITI-HC) and bikunin linked by a chrondroitin sulphate. By binding to hyaluronate, ITI-HC stabilises the extracellular matrix, but ITI-HC also binds to proteoglycans in follicular fluid. In vivo concentrations of ITI components in preovulatory follicular fluid, free as well as bound to hyaluronate or proteoglycan, are unknown. In order to quantify these components, 58 follicular fluids and 13 blood samples were collected in connection with in vitro fertilisation and embryo transfer treatment of 13 women. Quantitation of glycosaminoglycan-bound ITI-HC was performed after separation from free ITI in agarose gel. ITI components were determined by immunoelectrophoresis and hyaluronate by an ELISA method. The follicular fluid concentration of ITI was on average 70% of that in plasma and the concentration of hyaluronate remained low despite follicular production, suggesting that the production of hyaluronate is the rate-limiting step in the formation of the extracellular matrix of the oocyte-cumulus complex. In follicular fluid, the concentration of free ITI-HC was higher than that of glycosaminoglycan-bound ITI-HC. Addition of exogeneous hyaluronate doubled the amount of hyaluronate-bound ITI-HC, further supporting the notion that ITI in follicular fluid is not rate-limiting for cumulus expansion in vivo.

The occurrence of bikunin and ·1-microglobuli n was investigated in human ovary and Fallopian tubes. Bikunin and ·1-microglobulin are transcribed in the liver from a common gene. Bikunin immunoreactivity was detected in the zona pellucida. A positive reaction for bikunin was also observed in connective tissue of the oviduct. In addition, mast cells showed a more intense posi tive reaction than the surrounding connective tissue. Specific displaceable ·1-microglobulin immunoreactivity was revealed in the zona pellucida. The data suggest that bikunin and ·1- microglobulin are trapped in the zona pellucida.

Neutrophil gelatinase-associated lipocalin (NGAL) serum values have been shown to increase in preeclampsia. The goal of the present study was to evaluate changes in urinary NGAL concentrations during uncomplicated pregnancy and in cases of preeclampsia and hypertension.Fifty-one pregnant women who developed preeclampsia and 28 diagnosed with essential or gestational hypertension were investigated for urinary NGAL concentrations during pregnancy. As controls, 100 healthy pregnant women with uncomplicated singleton pregnancies were randomly selected. Urinary NGAL as well as urinary creatinine and albumin were measured by a standardized clinical chemistry platform (ARCHITECTUrinary NGAL concentrations increased during pregnancy in healthy pregnant women, whereas this increase was not detected in preeclampsia. In order to correct for diuresis, spot urine concentrations were also determined as NGAL/creatinine ratio. NGAL/creatinine ratio in pregnancy week 36–38 was significantly lower in preeclampsia than in healthy pregnant women or pregnant women with hypertension. NGAL urinary concentrations did not correlate with albumin concentration in urine.Urinary NGAL is not a valuable early biomarker for preeclampsia.

The regulation of cholecystokinin and somatostatin expression by vitamin D and cyclic AMP in the rat medullary thyroid carcinoma cell line CA-77 was investigated. Treatment with 100 nmol/l vitamin D did not affect cholecystokinin mRNA and peptide concentrations significantly; somatostatin mRNA level increased 6 times and the somatostatin peptide concentration increased 2-fold after 5 days of drug treatment. Under the same experimental conditions cyclic AMP increased cholecystokinin mRNA level 4.5 times and the cellular cholecystokinin-peptide concentration 2-fold; somatostatin mRNA and peptide concentrations were not significantly changed. Cyclic AMP stimulated peptide secretion from the cells were not affected by vitamin D, but cyclic AMP mediated increase in CCK peptide concentration was significantly inhibited by vitamin D (p < 0.05).

In competing athletes high intensity, high volume endurance exercise can induce transient depression in cardiac function and elevated cardiac biomarkers reflecting load, injury and adverse prognosis in patients. Acute cardiac effects of low intensity, high volume endurance exercise in non-athlete

The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0-1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.

Udgivelsesdato: 2009-Mar-9 BACKGROUND:: Hyponatremia is a frequent condition in elderly patients. In diagnostic workup, a 24-hour urine sample is used to measure urinary osmolality and urinary sodium concentration necessary to confirm the diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This study was undertaken to test the hypothesis that a spot urine sample would be sufficient for urinalysis. METHODS:: In nine patients with SIADH, morning spot and 24-hour urine samples were examined for osmolality and sodium concentration. Levels of arginine vasopressin, atrial natriuretic and brain natriuretic peptides, renin, and aldosterone were measured in the supine and upright positions of patients and compared with nine healthy age-matched control patients. RESULTS:: The patients had low plasma osmolality (median 266 mOsm/kg) and measurable levels of arginine vasopressin (median 1.8 pg/mL). Values of osmolality in the spot urine (median 298 mOsm/kg) and in the 24-hour urine (median 215 mOsm/kg) did not differ significantly; neither did sodium concentration (medians 80 mmol/L in the spot urine versus 45 mmol/L in the 24-hour urine). Patients had significantly elevated plasma levels of brain natriuretic peptide (P = 0.007), elevated mean arterial blood pressure (P = 0.03), and lower plasma levels of creatinine (P = 0.002) compared to the controls. CONCLUSION:: A spot urine sample seems to be sufficient to confirm the diagnosis of SIADH.

Background: We report our results for the systematic recording of all errors in a standard clinical laboratory over a 1-year period. Methods: Recording was performed using a commercial database program. All individuals in the laboratory were allowed to report errors. The testing processes were classified according to function, and errors were classified as pre-analytical, analytical, post-analytical, or service-related, and then further divided into descriptive subgroups. Samples were taken from hospital wards (38.6%), outpatient clinics (25.7%), general practitioners (29.4%), and other hospitals. Results: A total of 1189 errors were reported in 1151 reports during the first year, corresponding to an error rate of 1 error for every 142 patients, or 1 per 1223 tests. The majority of events were due to human errors (82.6%), and only a few (4.3%) were the result of technical errors. Most of the errors (81%) were preanalytical. Of the remainder, 10% were analytical, 8% were post-analytical, and 1% was service-related. Nearly half of the errors (ns550) occurred with samples received from general practitioners or clinical hospital wards. Identification errors were relatively common when non-technicians collected blood samples. Conclusions: Each clinical laboratory should record errors in a structured manner. A relation database is a useful tool for the recording and extraction of data, as the database can be structured to reflect the workflow at each individual laboratory. Clin Chem Lab Med 2009;47:1253–7.

The expression of gastrin/cholecystokinin (CCK) peptides and their precursors was examined in 16 medullary carcinomas of the human thyroid. Measurements with libraries of sequence-specific radioimmunoassays before and after enzymatic cleavage of extracts and chromatographic fractions showed that the carcinomas contained 1·7 pmol carboxyamidated CCK/g tissue (median; range 0·6–21·8 pmol/g), 0·9 pmol glycine-extended precursor/g (median; range < 0·2–2·3 pmol/g) and 2·3 pmol further COOH-terminal-extended proCCK/g (median; range 0·9–6·2 pmol/g). Neither carboxyamidated gastrins nor any progastrins could be measured. Gel and reverse-phase chromatography revealed only small molecular forms, i.e. > 90% of the amidated immunoreactivity eluted like non-sulphated CCK-8 or CCK-7. The results show that human medullary thyroid carcinomas synthesize CCK peptides. The predominance of non-sulphated CCK is unusual. Taken together with earlier observations from dogs and pigs, our results raise the possibility that small non-sulphated CCK peptides modulate thyroid C-cell secretion in an autocrine manner. Journal of Endocrinology (1990) 124, 501–506

Inter-alpha-trypsin inhibitor (ITI) consists of 3 polypeptides cross-linked by chondroitin sulphate, which is o-glycosidically linked to the smallest of the polypeptides, designated bikunin. Pre-alpha-trypsin inhibitor (p alpha I) consists of bikunin and a fourth polypeptide, also associated by chondroitin sulphate. Crossed immunoelectrophoresis (CIE) of plasma, using immunoglobulins to ITI, revealed 3 precipitation-lines, two of which increased in size during disease. Molecular mass determination by polyacrylamide gel electrophoresis showed that the immunoprecipitates contained mixtures of proteins. Therefore CIE is unfit for quantitation of the individual proteins related to ITI. Immunoblotting suggested that the plasma concentrations of p alpha I and of bikunin was increased in uraemia, rheumatoid arthritis and after trauma. The plasma concentrations of ITI and of p alpha I were decreased in a patient with endocarditis.

Infusion of an acidic amino acid, L-aspartate, to 10 volunteers resulted in transient, significant increases in urinary excretion of the major urinary trypsin inhibitor (p 2-microglobulin (p L-aspartate had reached the preinfusion level. Albumin excretion was unchanged indicating that the proteinuria was due to a decreased tubular reabsorption. The mechanism for the reversible tubular proteinuria is unknown. A simple pH effect due to alkalization of the urine was excluded, as NaHCO3 infusion was not followed by an increase in the excretion of the major urinary trypsin inhibitor and β2-microglobulin.

Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated immediately and resulted in a decreased amniotic fluid production from 30 weeks’ gestation. Even after the discontinuation of NSAID treatment, the amniotic fluid production normalized, and the woman delivered a healthy boy at 39 weeks 2 days’ gestation. Amniotic prolactin was measured at three occasions using an enzyme-linked immunosorbent assay. As in normal pregnancies, amniotic prolactin levels decreased by 80% from highest to lowest value in this case of resolving acute recurrent polyhydramnios.

Somatostatin is present in high concentrations in human seminal plasma. Semen was obtained from men with spinal cord injury by vibratory-and/or electrostimulation. The seminal somatostatin concentration and sperm motility rate depended on the location of the spinal cord lesion. In men with lesions at or above T6 the seminal plasma concentration was significantly decreased compared to healthy men and to patients with lesions below T6 (P < 0.005). The latter group did not differ from healthy men. Men with spinal cord lesions below T6 had significantly decreased sperm motility rates (P = 0.09) compared to patients with lesions at or above T6. Seminal somatostatin concentrations were similar in vibratory- and electrostimulated ejaculates. The seminal somatostatin concentration, semen volume, sperm count, motility and morphology in each patient was not affected when repeated vibratory ejaculations were performed at home.

The purpose of the work was to establish a reliable procedure for blood sampling from central venous catheters with a minimal loss of blood. Based on previous studies of potassium measurements, the routine procedure had been to discard 12 ml of blood. In order to clear the catheter from substances from the infusion including potassium, the catheters were first flushed with 5 ml of saline. Repeated samples in fractions of 3 ml for hematological analyses (ethylenediaminetetraacetic acid plasma; seven patients), coagulation tests (citrate plasma; seven patients) and for serum measurements (eight patients) showed that a discarded volume of 3 ml corresponding to at least six times the dead-space of the catheters was sufficient after initial flushing with saline.

The aim of this study was to examine, in elderly subjects, a possible association between age-related hearing impairment and vitamin B12 or folic acid status. Ninety-one consecutive subjects with pure age-related hearing impairment, 35 males and 56 females, with a median age of 78 years, range 67-88 years, were included in the investigation. All subjects underwent a thorough evaluation, including pure-tone, speech and impedance audiometry. Blood samples were drawn for determination of B12, folic acid and homocysteine and analysed by routine laboratory measurements. No significant differences in the blood parameters as a function of gender could be demonstrated and no correlations were found between B12 or folic acid and hearing levels averaged across the range 0.5-4 kHz. A weak correlation between hearing levels and homocysteine (r = 0.03; correlation coefficient 0.004) was found; however, a comparison of the hearing levels between those with increased and normal homocysteine failed to show any significant differences. In addition, no association between B12 and the speech recognition score could be found. This investigation therefore fails to demonstrate any association between hearing level and vitamin B12 or folic acid in elderly subjects.

Objective The aim of the study was to evaluate the impact of spinal cord injury on seminal plasma PSA concentration. Material Semen obtained from normal controls (n = 20) and patients (n = 16) with spinal cord injury. Results The concentration of prostate specific antigen in seminal plasma depended on the level of spinal cord injury, with significantly lower concentrations in patients with spinal cord lesions below T7 compared to both normal age-matched controls (P = 0.007) and patients with spinal cord injuries at or above T7 (P = 0.017). Conclusions The results add to the previously reported observations of the possible impact of neurogenic stimulation on prostate activity. More studies of neurogenic stimulation in prostate growth and development are warranted to further elucidate the possible impact of neurogenic factors in the development of prostatic diseases.

Synthesis of regulatory peptides has been described in a number of ovarian tumours. The recently isolated neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is expressed transiently in steroidogenic cells of normal rat ovary. In order to evaluate if ovarian tumours also synthesize PACAP, we investigated the expression and processing of pro-PACAP in 11 serous cystadenocarcinomas, one non-differentiated carcinoma, one borderline malignant and four adenomas. Using sequence specific radioimmunoassays and gel chromatography, we found that all tumours expressed PACAP-38 immunoreactivity. Ovarian cancers contained higher (P < 0.03) concentrations (median 0.9 pmol/g, range 0.5-1.6 pmol/g, n = 13) than benign tumours (median 0.5 pmol/g, range 0.4-0.6 pmol/g, n = 4). Chromatography showed that the tumours contained PACAP-38 and PACAP-31-38 suggesting a rather complete processing. By immunohistochemistry, few scattered PACAP positive cells in small clusters or as single cells were identified in the tumours.

Preterm births accounts for roughly 9% of all births worldwide and can have detrimental or even lethal consequences for the infant. However to develop new treatment that will lower the rate of preterm births, more knowledge is required on the factors contributing to the contraction and relaxation of the myometrium. The small conductance Ca2+-activated potassium channel subtype 3 (SK3) has been identified in the myometrium of several species including humans, mice and rats, but with great inter species variation of the expression pattern and regulation. The aim of this study was to investigate the expression of SK3 in the uterus of rats stimulated with 17β-estradiol and progesterone in order to get an in depth understanding of the rat uterine SK3. Using immunohistochemistry SK3 was localized to the glandular and luminal endometrial lamina epitheliali. Furthermore, a weak signal was observed in the myometrium. Using Western blot the protein level of SK3 was found to increase in uteri from animals treated with 17β-estradiol, an effect that was not reflected at the mRNA level. The levels of mRNA for SK3 were significantly lower in the uterus of 17β-estradiol-treated animals than in the uterus of ovariectomized animals. We conclude that the SK channels are present in the endometrial epithelium, and possibly also in the myometrium of the rat uterus. Furthermore, the hormonal effect on SK3 caused by 17β-estradiol includes divergent regulation at mRNA and protein levels.

Ødum L, Pildal I. Rehfeld pJF. Somatostatin in the boar reproductive system. Eur J Endocrinol 1994;130:515–21. ISSN 0804–4643 Somatostatin (SRIF) is a widely distributed regulatory peptide. Recently, it was shown that human seminal plasma contains high concentrations of SRIF. In order to find the cellular source of seminal SRIF we have examined the presence of SRIF in porcine urogenital tissues. The concentration of SRIF in male accessory reproductive tissues of 3-month-old pigs (N = 4) ranged from 1 to 17 nmol/kg. In the boar, only the prostate gland contained significant amounts of SRIF (median 7 nmol/kg, range 3–18 nmol/kg, N = 4). Testis and semen contained no SRIF. Gel chromatography of extracts of the male accessory sex glands and epididymis showed both SRIF-28 and SRIF-14, whereas urinary bladder contained mainly SRIF-14. In conclusion, the results show a considerable species, tissue and developmental variation in the expression of SRIF in the genitourinary tract. Lars Ødum, Department of Clinical Chemistry, Herlev Hospital, Herlev Ringvej 75, DK-2730, Denmark

Ascorbic acid is a water soluble antioxidant, that is itself oxidized to dehydroascorbic acid. In order to detect dehydroascorbic acid by amperometri it has to be reduced to ascorbic acid beforehand. This reduction was performed with dithioerytritol at pH = 6.0 for 10 min, which is a choice between optimal reaction rate and stability of ascorbic acid. The limit of detection of ascorbic acid is 1.1 pmol making the assay useful for determination of ascorbic and dehydroascorbic acid in small tissue biopsies. Results of this method and a colorimetric method were comparable.

1. 1. Biosynthesis of α1-microglobulin and inter-α-trypsin inhibitor was investigated in a human hepatoma cell line HepG-2. 2. 2. α1-Microglobulin was translated as a precursor common with the light chain of inter-α-trypsin inhibitor. 3. 3. α1-Microglobulin was synthesized and secreted into the growth medium within 30 min. 4. 4. Processing of inter-α-trypsin-inhibitor-related proteins appeared slow and incomplete. The light chain was connected via a chondroitinsulphate to a heavy chain to form a 125,000- Mr protein and secreted within 1–4 hr.

Insight in the mechanisms of peptide hormone expression has grown explosively by elucidation of gene, mRNA and preprohormone structures for most hormone systems during the 1980s. In addition, information about the structure and substrate specificity of many prohormone processing enzymes is rapidly accumulating in these years. The preprohormones vary considerably in size and organization from poly- to monoprotein structures. According to the structural organization and sequence homology the hormones are grouped in families. The prohormones are processed to bioactive peptides by multiple enzymatic modifications during the intracellular transport from the rough endoplasmatic reticulum to the mature secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. The same prohormone may be expressed in several different cell types that process the precursor in entirely different ways. Awareness of such cell-specific processing patterns is important for the understanding of ectopic synthesis in neuroendocrine tumours.

The presence of inter-alpha-trypsin inhibitor in the urinary tract was investigated by immunohistochemistry. A positive reaction for inter-alpha-trypsin inhibitor was found in the proximal convoluted tubules of human kidney, probably representing the reabsorbed protein. In addition, inter-alpha-trypsin-inhibitor immunoreactivity was also demonstrated in human and rat mast cells.

Inter-alpha-trypsin inhibitor (I alpha I) and the immunologically related prealbumin-like-migrating proteinase inhibitor (pA-PI) were investigated by crossed immunoelectrophoresis in sera from 68 persons with myocardial infarction, neoplastic diseases, inflammatory diseases, collagenosis, cirrhosis of the liver or uremia. The concentration of pA-PI in serum increased during each of these diseases (p less than 0.01). The concentration of I alpha I was significantly decreased in patients with cirrhosis (p less than 0.01). In day to day studies of a patient with myocardial infarction, a patient with erysipelas and a postoperative patient the concentration of I alpha I was low normal to decreased in the first days of the conditions and increased thereafter to high normal values. A comparison of the concentration of pA-PI with the excretion of the immunologically identical urinary proteinase inhibitor (UPI) showed that the excretion could not be caused by simple overflow of pA-PI in the kidney. The excretion of UPI followed closely the acute-phase-response, as measured by serum C-reactive protein.

Insight in the mechanisms of peptide hormone expression has grown explosively by elucidation of gene, mRNA and preprohormone structures for most hormone systems during the 1980s. The preprohormones vary considerably in size and organization from poly- to mono-protein structures. According to the structural organization and sequence homology the hormones are grouped in families. The prohormones are processed to bioactive peptides by multiple enzymatic modifications during the intracellular transport from the rough endoplasmatic reticulum to the mature secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. The same prohormone may be expressed in several different cell-types that process the precursor in entirely different ways. Awareness of such cell-specific processing patterns is important for the understanding of ectopic synthesis in neuroendocrine tumours.

1. 1. Slow migrating proteinase inhibitors were isolated from pathological human urine. 2. 2. The N-terminal amino acid sequence including 23 amino acids was identical to the one in pancreatic secretory trypsin inhibitor. 3. 3. The slow migrating proteinase inhibitors occurred in 3 forms with different electrophoretic mobility. 4. 4. Time of flight mass spectrometry showed that the M w of one of the forms was 6241 while the M w of another form was 5923. 5. 5. The K i of complexes with trypsin was determined to be 1 × 10 −10 M, with chymotrypsin and plasmin K i was 1 × 10 −7 M. Elastase, kallikrein and thrombin were not inhibited.

Based on the amino-acid sequence it has been proposed that ovalbumin is a proteinase inhibitor. The inhibitory activity against trypsin, chymotrypsin, pancreatic elastase, plasmin, thrombin and pancreatic kallikrein was tested, but none of these proteinases were inhibited by ovalbumin. A commercial preparation of ovalbumin contained an impurity with trypsin inhibitory activity. This impurity was probably ovomucoid.

The concentration in serum of inter-alpha trypsin inhibitor (I alpha I) and its immunologically related inhibitor, the prealbumin-like proteinase inhibitor (pA-PI), was investigated by quantitative crossed immunoelectrophoresis (CIE) in 33 healthy persons. The corresponding urinary excretion over a 4 h period of the immunologically related urinary proteinase inhibitor (UPI) was measured by rocket immunoelectrophoresis. The concentration of pA-PI increased significantly (p less than 0.001) with age whereas that of I alpha I and the urinary excretion of UPI were independent of age. There was no significantly difference in the concentration of the inhibitors in serum between the sexes, but females were found to have a lower urinary excretion of UPI than males (p less than 0.05). Furthermore we found no significant variation in the concentration of the inhibitors during the course of the day or from day to day over a 5 day period. Results obtained by rocket immunoelectrophoresis correlated well with enzymatically measured trypsin inhibitory activity.

By means of a sensitive electrophoretic technique for the detection of proteinase inhibitors three slowly migrating proteinase inhibitors (SMPI) were discovered in some samples of pathological urine. SMPI 1 migrated in the beta 2-zone whereas SMPI 2 and SMPI 3 appeared in the anodal and cathodal gamma-zone, respectively. Only SMPI 1 and 2 were examined in detail. These were found to inhibit tryptic and elastolytic digestion, but not chymotryptic or plasminolytic digestion of casein. Immunological investigations revealed no similarity to normally occurring proteinase inhibitors in serum and urine. The SMPIs from one sample of urine were partially purified by DEAE-Sephadex ion exchange chromatography, followed by gel filtration on Sephacryl superfine 200. This procedure did not separate the two inhibitors. The molecular masses were estimated to be 25 000 Da by gel filtration, and 23000-26500 Da by SDS polyacrylamide gel electrophoresis.

Normal cerebrospinal fluid (CSF) contains several of the proteinase inhibitors present in human serum. ai-proteinase inhibitor, ar macroglobulin, inter-a-trypsin inhibitor and a2antiplasmin have so far been demonstrated. I. 2 The concentration of these inhibitors in normal CSF is approximately one hundred times lower than in normal serum.' The presence of antithrombin III and a previously unrecognised trypsin inhibitor migrating in the region of albumin is reported here.

Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotein structures. According to their structural organization and sequence homology, hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptide-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently, the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PIA), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.