Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves' orbitopathy: a small prospective pilot study.

PURPOSE: Chronic GC administration has numerous side effects, but little is known about the side effects of their short-term use (< 3 months)-particularly, when high doses are involved, as in the treatment of Graves' orbitopathy (GO). We investigated the effects of short-term, high-dose GC on bone turnover markers, bone mineral density (BMD), and trabecular bone scores (TBS). METHODS: Eleven patients (10 females and 1 male; median age 56 years) with active GO who were candidates for treatment with intravenous (iv) methylprednisone were consecutively enrolled. All patients were pretreated with a loading dose of 300,000 units of cholecalciferol, then given a median cumulative dose of 4.5 g (range 1.5-5.25 g) iv methylprednisone. Biochemical parameters of bone metabolism (25OHD3, PTH, P1NP, CTX and bALP) were measured at the baseline, and then 1 week and 1, 3, 6 and 12 months. BMD and TBS were obtained by X-ray absorptiometry (DXA) at the baseline and at 6 and 12 months. On DXA image, morphometric vertebral fracture assessment (VFA) was done. RESULTS: There were no significant changes in PTH, bALP or P1NP. A significant drop in CTX was seen at 1 month (down Δ49.31% from the baseline, p = 0.02), with a return to the baseline at the 3-month measurement. There was a moderate (not significant), but persistent reduction in P1NP. No changes in BMD or TBS came to light. No vertebral fractures were documented. CONCLUSIONS: Short-term, high-dose GC treatment caused a rapid, transient suppression of bone resorption, with no effects on BMD or bone micro-architecture (TBS).

Biomarkers, imaging and disease activity indices in patients with early axial spondyloarthritis: the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) Study.

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

25-Hydroxycholecalciferol response to single oral cholecalciferol loading in the normal weight, overweight, and obese.

UNLABELLED: After a single cholecalciferol load, peak serum 25-hydroxycholecalciferol (25OHD) is lower in individuals with a higher body mass index (BMI), probably due to it being distributed in a greater volume. Its subsequent disappearance from the serum is slower the higher the individual's BMI, probably due to the combination of a larger body volume and a slower release into the circulation of vitamin D stored in adipose tissue. INTRODUCTION: The aim of the study is to examine 25-hydroxycholecalciferol (25OHD) response to a single oral load of cholecalciferol in the normal weight, overweight, and obese. METHODS: We considered 55 healthy women aged from 25 to 67 years (mean ± SD, 50.8 ± 9.5) with a BMI ranging from 18.7 to 42 kg/m(2) (mean ± SD, 27.1 ± 6.0). The sample was divided into three groups by BMI: 20 were normal weight (BMI ≤ 25 kg/m(2)), 21 overweight (25.1 ≤ BMI ≤ 29.9 kg/ m(2)), and 14 obese (BMI ≥ 30 kg/m(2)). Each subject was given 300,000 IU of cholecalciferol orally during lunch. A fasting blood test was obtained before cholecalciferol loading and then 7, 30, and 90 days afterwards to measure serum 25OHD, 1,25 dihydroxyvitamin D [1,25 (OH)2D], parathyroid hormone (PTH), calcium (Ca), and phosphorus (P). Participants' absolute fat mass was measured using dual energy X-ray absorptiometry (DEXA). RESULTS: The fat mass of the normal weight subjects was significantly lower than that of the overweight, which in turn was lower than that of the obese participants. Serum 25OHD levels increased significantly in all groups, peaking 1 week after the cholecalciferol load. Peak serum 25OHD levels were lower the higher the individuals' BMI. After peaking, the 25OHD levels gradually decreased, following a significantly different trend in the three groups. The slope was similar for the overweight and obese, declining significantly more slowly than in the normal weight group. In the sample as a whole, there was a weakly significant negative correlation between fat mass and baseline 25OHD level, while this correlation became strongly significant at all time points after cholecalciferol loading. CONCLUSIONS: The lower peak 25OHD levels seen in the obese and overweight is probably due to the cholecalciferol load being distributed in a larger body volume. The longer persistence of 25OHD in their serum could be due to both their larger body volume and a slower release into the circulation of the vitamin D stored in their adipose tissue.

Effect of a single injection of testosterone enanthate on 17ß estradiol and bone turnover markers in hypogonadal male patients.

PURPOSE: Several clinical studies testify the critical role played by estrogens in male bone metabolism. The aim of our study is to assess the effect of a single injection of testosterone enanthate in a group of hypogonadal men on 17ß estradiol serum levels and some bone metabolic parameters. METHOD: Twenty-one hypogonadal males were given one testosterone enanthate injection (250 mg). Blood samples were drawn before the injection and after 1, 2 and 3 weeks. The following variables were measured: Total testosterone (TT), 17ß estradiol (17ß E2), Sex hormone binding globulin, total alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen (CTx). RESULTS: After testosterone injection, both TT and 17ß E2 increased, peaking 1 week after the injection. Individual observation of the response of 17ß E2 to testosterone showed that a subgroup (n = 9) failed to respond with any increase in 17ß E2 at any of the weekly tests (group E2-), while the remainder (n = 12) showed a significant increase in 17ß E2, which reached a mean value three times higher than at baseline (group E2+). The E2- patients reached a TT peak lower than that observed in the E+ group. CTx serum levels declined progressively in the E2+ group, reaching the significance (p = 0.03) at the end of the study, while it did not change in E- group. CONCLUSION: This study suggests that a single injection of testosterone might have different effects on the production of endogenous estrogens, and a significant reduction of bone resorption parameters takes place only in the patients who show a significant increase of 17ß estradiol in response to testosterone administration.

Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination.

BACKGROUND: The pathological significance and the diagnostic usefulness of intrathecal κ and λ free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated. METHODS: Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RRMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, κFLC and λFLC concentrations and indexes were evaluated. All RRMS performed MRI to estimate white and grey matter (WM) pathology. RESULTS: In HC, no intrathecal κ or λ FLC synthesis was found, and κFLC and λFLC Indexes were reciprocally correlated (r = 0.67, p < 0.001). In RRMS, intrathecal κFLC or λFLC synthesis was demonstrated in respectively 66% and 43% of the cases, the Qκ/λ ratio was significantly higher compared to HC (17.0 ±â€¯31.3 vs 0.79 ±â€¯0.20, p < 0.001) and the correlation between κFLC Index and λFLC Index was weak (r:0.38, p < 0.05). Intrathecal IgG synthesis was associated with κFLC Index (IgG Index: r2 = 0.53, ß = 0.73, p < 0.001; IgGLOC: r2 = 0.37, ß = 0.61, p < 0.001; IgGIF: r2 = 0.69, ß = 0.83, p < 0.001), but not with λFLC Index, while intrathecal IgM synthesis correlated with λFLC Index (IgM Index: r = 0.41, p < 0.001; IgMLOC: r = 0.34, p < 0.005; IgMIF: r = 0.45, p < 0.001), but not with κFLC Index. 26% of RRMS patients without CSF-restricted IgGOB had increased κFLCLOC. Finally, no associations were observed between any CSF and MRI parameters. CONCLUSIONS: The demonstration of intrathecal κFLC synthesis may further improve the diagnostic usefulness of CSF examination in RRMS. The marked increased in Qκ/λ further suggests a deregulated B-cell activation in MS pathology.

An open population screening study for HFE gene major mutations proves the low prevalence of C282Y mutation in Central Italy.

BACKGROUND: The C282Y mutation in the HFE gene is responsible for most cases of hereditary haemochromatosis. AIM: To investigate the allele frequency of HFE mutations and the associations between mutations and cases of iron overload or liver diseases in an open population of Central Italy. METHODS: A total of 502 individuals over 8 years of age, comprising 203 males and 299 females, who were residents in Arsita (a small town in Central Italy), were assayed for: C282Y, H63D and S65C mutations of the HFE gene by TaqMan probes; body mass index, serum ferritin, transferrin saturation, transaminases, GGT, glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, HBV and HCV serum markers. Information was obtained on alcohol intake. Liver ultrasound was performed in 334 (67%) subjects. RESULTS: The allele frequencies for C282Y, H63D and S65C were 2%, 15%, and 0.01%, respectively. C282Y/wt was found in 19 subjects (4%), H63D/wt in 127 (25%), H63D/H63D in 11 (2%) and S65C/wt in one (2.0 per thousand). No homozygosity for C282Y or compound mutation (C282Y/H63D) was found in the study population, but 27 subjects (5%) had TfSat >45% (including 10 subjects with high serum ferritin). Overall, 49 subjects (9.8%) were HCV-RNA-positive. Logistic regression analysis indicated that male gender (P = 0.000) and hepatic steatosis (P = 0.017) were independent variables correlating to a high serum ferritin. CONCLUSION: C282Y HFE mutation is less frequent in Central Italy than in Northern Italy.

[Acute effects of environmental pollution on the urban vigilants airways]. / Effetto acuto dell'inquinamento ambientale sulle vie aeree in vigili urbani.

AIM OF THE STUDY: The purpose of this study was to evaluate whether the acute exposure to air pollution, in a group of policemen of Padua, is correlated with increased inflammatory biomarkers (exhaled nitric oxide, feNO) and alterations of bronchiolar cells (assessed by CC16 Clara cell-specific protein). METHODS: We studied 44 healthy, non-smokers divided in exposed to traffic and controls (office workers). Before and after the Monday shift serum and urinary concentration of CC16, feNo and spirometry were measured in each subject. Data on air pollutants, PM2.5, PM10, SO2, NO2, CO, O3 were collected from official bulletin online (ARPAV). RESULTS: In exposed policemen serum CC16 decreased after shift (before 4.6 +/- 0.2 vs after 6.4 +/- 0.8 ng/ml, = 0.02), while feNO increased significantly (33.2 +/- 4.4 vs 29.7 +/- 3.9 ppb, p = 0.02). feNO cross-shift changes were positively correlated with environmental SO2 levels (rho = 0.48; p = 0.01). CONCLUSIONS: Our results suggest that in healthy and nonsmokers subjects the exposure to air pollution is associated with subclinical airway inflammation and decrease of bronchiolar epithelium function.

Diagnostic and prognostic value of low percentage of glycosylated ferritin in acquired hemophagocytic lymphohistiocytosis: A single-center study.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome characterized by an excessive immune activation. Glycosylated ferritin (GF) level has been proposed as highly specific of HLH. METHODS: We have studied 12 subjects with HLH according to the HLH-04 trial criteria and 11 patients with a clinical and laboratoristic suspicion of HLH. The percentage of GF was measured by an in-house assay. RESULTS: The only biomarkers that were significantly different in the two groups were fraction of GF (P<.001) and the presence of hemophagocytosis in bone marrow (P=.006). Subjects with HLH had significantly lower percentage of GF than patients with other inflammatory conditions mimicking HLH. A fraction of GF ≤20% was strongly consistent with a diagnosis of HLH. CONCLUSIONS: Fraction of GF is useful to identify subjects at high risk for early death and therefore in need of early treatment.

Mannose-binding lectin 2 (Mbl2) gene polymorphisms are related to protein plasma levels, but not to heart disease and infection by Chlamydia.

The presence of the single nucleotide polymorphisms in exon 1 of the mannose-binding lectin 2 (MBL2) gene was evaluated in a sample of 159 patients undergoing coronary artery bypass surgery (71 patients undergoing valve replacement surgery and 300 control subjects) to investigate a possible association between polymorphisms and heart disease with Chlamydia infection. The identification of the alleles B and D was performed using real time polymerase chain reaction (PCR) and of the allele C was accomplished through PCR assays followed by digestion with the restriction enzyme. The comparative analysis of allelic and genotypic frequencies between the three groups did not reveal any significant difference, even when related to previous Chlamydia infection. Variations in the MBL plasma levels were influenced by the presence of polymorphisms, being significantly higher in the group of cardiac patients, but without representing a risk for the disease. The results showed that despite MBL2 gene polymorphisms being associated with the protein plasma levels, the polymorphisms were not enough to predict the development of heart disease, regardless of infection with both species of Chlamydia.

Alendronate prevents further bone loss in renal transplant recipients.

The aim of this study was to investigate the effects of alendronate, calcitriol, and calcium in bone loss after kidney transplantation. We enrolled 40 patients (27 men and 13 women, aged 44.2 +/- 11.6 years) who had received renal allograft at least 6 months before (time since transplant, 61.2 +/- 44.6 months). At baseline, parathyroid hormone (PTH) was elevated in 53% of the patients and the Z scores for bone alkaline phosphatase (b-ALP) and urinary type I collagen cross-linked N-telopeptide (u-NTX) were higher than expected (p < 0.001). T scores for the lumbar spine (-2.4 +/- 1.0), total femur (-2.0 +/- 0.7), and femoral neck (-2.2 +/- 0.6) were reduced (p < 0.001). After the first observation, patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical, biochemical, and densitometric parameters were reassessed 1 year later. During this period, bone density decreased at the spine (-2.6 +/- 5.7%;p < 0.01), total femur (-1.4 +/- 4.2%; p < 0.05), and femoral neck (-2.0 +/- 3.0%; p < 0.001). Then, the patients were randomized into two groups: (1) group A-10 mg/day of alendronate, 0.50 microg/day of calcitriol, and 500 mg/day of calcium carbonate; and (2) group B-0.50 microg/day of calcitriol and 500 mg/day of calcium carbonate. A further metabolic and densitometric reevaluation was performed after the 12-month treatment period. At the randomization time, group A and group B patients did not differ as to the main demographic and clinical variables. After treatment, bone turnover markers showed a nonsignificant fall in group B patients, while both b-ALP and u-NTX decreased significantly in alendronate-treated patients. Bone density of the spine (+5.0 +/- 4.4%), femoral neck (+4.5 +/- 4.9%), and total femur (+3.9 +/- 2.8%) increased significantly only in the alendronate-treated patients. However, no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects. No drug-related major adverse effect was recorded in the two groups. We conclude that renal transplanted patients continue to loose bone even in the long-term after the graft. Alendronate normalizes bone turnover and increases bone density. The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects.

Effect of timing of administration on the plasma ACE inhibitory activity and the antihypertensive effect of quinapril.

To assess whether timing of administration can influence the antihypertensive effect of quinapril, 18 patients with hypertension were studied with noninvasive ambulatory blood pressure monitoring. Quinapril, 20 mg, was given at 8 AM or 10 PM for 4 weeks in a double-blind crossover fashion. To study the pattern of angiotensin converting enzyme (ACE) inhibition with the two treatment regimens, plasma ACE activity was measured in seven subjects 2, 4, 8, 12 and 24 hours after quinapril administration. The 24-hour blood pressure profiles showed a more sustained antihypertensive action with the evening administration of quinapril compared with the morning administration of quinapril; as with the morning administration, a partial loss of effectiveness was observed during nighttime hours. Measurement of ACE activity showed that evening administration caused a less pronounced but a more sustained decline of plasma ACE. These findings show that 20 mg quinapril given once daily is effective in lowering blood pressure levels throughout a 24-hour period. The evening administration seems to be preferable because it causes a more favorable modulation of ACE inhibition and therefore determines a more homogeneous 24-hour blood pressure control.

Strategies for the early diagnosis of acute myocardial infarction using biochemical markers.

We evaluated different diagnostic strategies for the early diagnosis of acute myocardial infarction, combining sensitivity and specificity of different markers evaluated singly and using combination testing in parallel and serial modes. Myoglobin, cardiac troponin I (TnI), creatine kinase (CK), and CK-MB mass were tested in blood samples from 26 patients with acute myocardial infarction collected at admission (T0; mean = 3.3 hours from the onset of chest pain) and 3 and 6 hours later. The comparison group was made up of 70 patients with renal failure, skeletal muscle diseases, stable angina, unstable angina, and chest pain of nonischemic origin. Single tests showed different sensitivities in relation to the different release kinetics; myoglobin was the most sensitive (69% at T0) although less specific (46%), and TnI showed the highest specificity (90%) and a sensitivity of 54%. Combination testing in a parallel mode using myoglobin and TnI or CK-MB had the same sensitivity and specificity as myoglobin tested singly. The best combination in a serial mode is myoglobin and TnI (at T0 sensitivity, 54%; specificity, 98%), as confirmed by the analysis of the positive predictive value, the negative predictive value, and the accuracy evaluated as a function of different disease prevalences.

An unidentified pancreatic cancer cell product alters some intracellular pathways of glucose metabolism in isolated rat hepatocytes.

In this study we assessed whether conditioned media from a human pancreatic cancer cell line (MIA PaCa 2) can interfere with some intracellular pathways involved in glucose metabolism in isolated rat hepatocytes. The hepatocytes, isolated from Male Wistar rats, were incubated with MIA PaCa 2-conditioned or nonconditioned media. Conditioned and nonconditioned hepatocytes were run for 120 min in the presence or absence of insulin (100 mM) and were sampled at fixed time intervals. Supernatant glucose levels decreased to a similar extent over time in both conditioned and nonconditioned hepatocytes, while lactate levels significantly increased in nonconditioned hepatocytes with respect to conditioned hepatocytes. A pyruvate kinase activity increase was observed only in nonconditioned hepatocytes and was biphasic in nature, since this increased activity was detected both after a few and after 30 min following insulin stimulation. The cyclic AMP level increase was significantly higher in conditioned than in nonconditioned hepatocytes. It appears that MIA PaCa 2 cells produce a factor(s) that may interfere with one of the insulin-mediated intracellular pathways of glucose metabolism, namely, glycolysis. This detrimental effect on glycolysis is supported by the blunted rise in lactate concentration in the medium after the glucose challenge. This substance(s) probably transfers its signal inside the target cells, activating the adenylate cyclase pathway. These results support the hypothesis that pancreatic cancer is the cause rather than the consequence of diabetes mellitus.

Clinical importance of lipase determination by the turbidimetric procedure as compared with determination by a chromatrographic procedure.

The turbidimetric determination of serum lipase activity was compared with the chromatographic determination in three groups of patients, including patients affected by hepatic diseases, patients affected by pancreatic diseases and a control group. The two methods were also compared in the determination of lipase activity of human leucocytes in vitro. The results show that there is a good statistical correlation of lipase turbidimetrically determined at pH 9.15 and amylase in serum of normal individuals and in serum of patients with pancreatic diseases. There is no correlation between amylase and chromatographically determined lipase. The other types of lipase activity determined, i.e. turbidimetrically assayed at pH 5.5 and chromatographically assayed both at pH 5.5 and at pH 9.15, might be related to a different non-pancreatic enzymatic activity which is likely to lack diagnostic value. This suggests that methods of lipase determination based, for instance, on fatty acid liberation are of limited value in clinical studies on lipase.

Precipitation method for separating and quantifying bone and liver alkaline phosphatase isoenzymes.

We evaluated a method for quantifying bone isoenzyme of alkaline phosphatase (ALP) which utilizes wheat-germ lectin to precipitate this fraction. In precision studies, CVs ranged from 3.2 to 11.4% (within-day) and from 3.7 to 11.5% (day-to-day). The assay procedure was linear to 1100 U/L and was easily adapted to automated kinetic measurement. Comparison of the precipitation method with an affinity electrophoretic method, which utilizes cellulose acetate as a support, demonstrated a satisfactory coefficient of correlation (r = 0.886). The reference range was determined in sera from 188 healthy adult subjects. The distribution of bone ALP values was also studied in 73 healthy children and in 30 healthy adolescents. To evaluate the clinical applicability of the method, the bone isoenzyme was determined in samples from several groups of subjects (pregnant women, patients with hepatobiliary diseases, patients with hepatocellular carcinoma without skeletal involvement, and patients with bone, liver or lymph node metastases). We found the method suitable for routine determination of bone alkaline phosphatase and for the screening of bone metastases. Because of its technical simplicity and satisfactory analytical performance, it can be used instead of the heat-inactivation procedure.

Troponin T as a marker of ischemic myocardial injury.

A study was undertaken to evaluate the clinical relevance of serum troponin T (TnT) as a marker of ischemic myocardial injury, using a new automated enzyme immunoassay. The reference range for serum TnT was established by measuring serum TnT concentrations in blood obtained from 262 healthy subjects. The serum concentration of TnT was compared to serum creatine kinase activity, creatine kinase MB (mass and activity), myoglobin concentration, and lactate dehydrogenase activity: in 77 patients with myocardial infarction (55 received thrombolytic treatment); in 32 patients with unstable angina; in 30 patients with nonischemic heart diseases; and in 40 patients with skeletal muscle injuries. Our findings showed that: a) 99% of healthy blood donors had TnT concentrations < 0.10 micrograms/L; b) the test had a high clinical efficiency in the diagnosis of acute myocardial infarction, with a sensitivity of 1.0 and a specificity of 0.88 at a decision level of 0.20 micrograms/L; c) serum TnT had a later peak value (8-38 h), but a wider diagnostic window (> 126 h) than the traditional markers considered in the study; d) serum TnT had an excellent sensitivity in the detection of microinfarctions in patients with unstable angina pectoris; e) the release patterns of serum TnT were qualitatively different in perfused versus nonperfused patients. Peak serum TnT values and time to peak values were statistically different (p = 0.0336 and p = 0.0001) in reperfused and nonreperfused AMI patients, respectively; f) a ratio of serum TnT at 16 h to serum TnT at 32 h after chest pain > 1 provided a good indication of reperfusion in thrombolytic treatment (94% efficiency).

Enzyme immunoassay for pancreatic lipase: comparison with turbidimetric method in pancreatic diseases.

We report the results of the analytical and clinical evaluation of a specific enzyme immunoassay for determination of human pancreatic lipase, in comparison with a turbidimetric method, in pancreatic pathology. Under standardized conditions of incubation time and temperature we found intraassay coefficient of variation (CV) of 1.3, 3.2, 2.1% at means = 18.7, 43.7, 224 micrograms/L and interassay CV of 2.8, 4.6, 3.0% at means = 19, 42.6, 230 micrograms/L, respectively. In general, a good correlation (r = 0.97) was found between lipase determined as a protein or through its catalytic activity. No significant correlation (r = 0.38) was observed with samples containing low concentration of lipase (up to 18 micrograms/L). We conclude that the turbidimetric method is reliable for routine determinations in the diagnosis of acute pancreatic pathology. However, the better sensitivity of the immunochemical assay should provide additional information for monitoring pancreatic insufficiency.

Low molecular mass proteins and urinary enzymes in amniotic fluid of healthy pregnant women at progressive stages of gestation.

OBJECTIVES: Amniotic fluid alpha1-microglobulin (alpha1-m) and beta2-microglobulin (beta2-m) levels, as well as N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities, were measured in the course of uncomplicated pregnancies to assess their variations as gestation progresses. DESIGN AND METHODS: Samples were obtained from 141 healthy pregnant women divided into three groups on the basis of gestational stage. Quantitative estimation of proteins was performed immunometrically and enzyme activities were determined spectrophotometrically. RESULTS: It was found that, during pregnancy, alpha1-m and beta2-m concentrations as well as AAP activity significantly decrease, although their reduction patterns vary. Controversial results were found for NAG activity: the normalization of values for amniotic fluid creatinine significantly changed the reduction pattern of this enzyme. No statistically significant differences were found between male and female fetuses for amniotic fluid values of the biochemical substances studied. CONCLUSIONS: The behavior observed for alpha1-m, beta2-m, and AAP might be linked to the progressive development and maturation of fetal renal tubular function. Amniotic fluid total NAG activity seems not to depend only on fetal urinary excretion.

New and traditional serum markers of bone metabolism in the detection of skeletal metastases.

OBJECTIVES: The evaluation of "new" and "traditional" markers of osteoblastic and osteoclastic activity, in patients with bone metastases. DESIGN AND METHODS: Our series consist of 40 patients with clinical, radiological, and scintigraphic evidence of bone metastases, and 40 age-matched healthy subjects. In all samples, traditional markers were evaluated by measuring total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TrACP) activity, and osteocalcin (BGP) concentration. To assess new biochemical bone markers, bone isoenzyme of alkaline phosphatase (ALP-B) activity, carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal telopeptide of type I collagen (ICTP) concentrations were measured. RESULTS: Our findings showed that the best diagnostic efficiency is provided by ICTP (0.94) followed by total ALP (0.90), ALP-B (0.80), and TrACP (0.76). The efficiency of BGP and PICP was, instead, very low (0.64 and 0.60, respectively). CONCLUSION: Our results confirm the utility of the new serum markers such as ALP-B and ICTP assays in detecting bone metastases.