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Serum resistance of Pasteurella multocida in avian and porcine sera, and comparative virulence investigations of selected serum-sensitive and resistant strains in chickens.

Growth in serum of Pasteurella multocida and related species in chicken, turkey, duck and pig sera were compared, and selected serum-resistant and serum-sensitive strains were inoculated into 18-week-old layers. Eighty-seven field strains of Pasteurella spp. and nine reference strains representing different clones defined by restriction endonuclease analysis (REA) profiles were used in the study. Serum activity was measured by changes in the optical density (OD) of the serum after inoculation and incubation at 41 degrees C for chicken, turkey and duck serum and 39 degrees C for pig serum. Serum activity was measured by comparison with previously determined serum-resistant (P-1059) and serum-sensitive (CU vaccine) strains, and classified into highly serum-resistant, moderately serum-resistant and serum-sensitive. Strains of the same REA type were found to have identical growth curves and the same maximum OD values when tested in serum from the same host species. Turkey serum was shown to be less inhibitory to a wide range of P. multocida strains than chicken, duck and pig sera. Serum-resistant strains were demonstrated among avian as well as mammalian strains. Among the avian strains, the proportion of serum-resistant strains was higher in outbreak strains than in strains from apparently healthy carriers. Removal of the capsule from selected strains by hyaluronidase treatment failed to change the serum activity. The most severe lesions in experimentally infected chickens were produced by a serum-resistant strain; however, lesions were also found in chickens infected by serum-sensitive strains, indicating the involvement of multiple factors in the virulence of P. multocida. Further investigations on serum resistance are indicated in order to relate other host and bacterial factors responsible for the development of fowl cholera.

Animals↗

Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation. OBJECTIVES: To investigate whether serum IL-8 level was a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP and to assess whether IL-8 was a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP, nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration were treated with levamisole for 0.5-6.0 months and their serum IL-6 and IL-8 levels were measured after treatment. RESULTS: We found that 28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16) nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142) EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-6.0 months could significantly reduce the mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P < 0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/- 17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001). CONCLUSIONS: Because measurement of the serum IL-8 level can detect more OLP patients with an abnormal serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP. Levamisole can modulate both the serum IL-6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.

Acute Disease↗

Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery.

Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.

Child↗

Serum leptin levels in healthy ageing men: are decreased serum testosterone and increased adiposity in elderly men the consequence of leptin deficiency?

OBJECTIVE: The limited information on serum leptin levels in elderly men suggests the occurrence of an age-related decrease, with disruption of the relationship between fat mass and leptin levels. A relative leptin deficiency might thus be implicated in the increase of fat mass and decrease of serum testosterone levels in elderly men. Therefore, we have reevaluated the age-related changes in serum leptin levels and their relationship with adiposity and androgen levels in a large group of community dwelling men. SUBJECTS AND MEASUREMENTS: Serum leptin and androgen levels were measured in 271 healthy, ambulatory elderly men (median age 74 years), as well as in 61 middle-aged (median 43 years) and 40 young (median 25.5 years) controls. Adiposity was assessed by anthropometrical measurements (body mass index; BMI) and by estimation of fat mass by the bio-impedance method. RESULTS: Serum leptin levels, whether or not adjusted for BMI, were found to increase with age, the values tending to level off after the age of 45 years, and were strongly correlated to BMI (r = 0.77) and fat mass assessed by the bio-impedance method (r = 0.81). Linear regression analysis showed a similar slope for the relationship between BMI and serum leptin in the three age groups. Multiple linear regression analysis indicated BMI, age and serum insulin, but not serum testosterone, as significant independent correlates of serum leptin. Serum (free) testosterone levels were negatively correlated with age and serum leptin, also after partialization for BMI: rank correlation coefficients vs. age and serum leptin, respectively, were - 0.20 (P < 0.001) and - 0.16 (P < 0.01) for total testosterone and - 0.60 (P < 0.001) and - 0.23 (P < 0.001) for free testosterone. Dehydroepiandrosterone sulphate (DHEAS) and leptin levels emerged as significant independent correlates in a multiple linear regression model for total serum testosterone; BMI and serum insulin became highly significant correlates in the same model when leptin was omitted from the independent variables. CONCLUSION: Ageing in men is accompanied by a rise of serum leptin levels with a maintained strong association between serum leptin and adiposity in elderly men. Testosterone does not appear to be a major determinant of serum leptin in healthy men, while leptin does emerge as a negative correlate of serum testosterone. Increased fat mass and decreased testosterone production in elderly men cannot be attributed to a relative leptin deficiency.

Adult↗

HIV and other predictors of serum folate, serum ferritin, and hemoglobin in pregnancy: a cross-sectional study in Zimbabwe.

BACKGROUND: Folate and iron status and hemoglobin concentrations are important to maternal and infant health. OBJECTIVE: Our goal was to identify predictors of serum folate, serum ferritin, and hemoglobin. DESIGN: This was a cross-sectional study of 1669 pregnant women (22-35 wk of gestation) in Harare, Zimbabwe, who were receiving prenatal care. The statistical effects of age, season, gestational age, gravidity, HIV-1 infection, malaria parasitemia, and serum alpha1-antichymotrypsin (ACT) on serum folate, serum ferritin (log10 transformed), and hemoglobin were estimated by using multiple linear regression analyses. RESULTS: Serum folate (x: 11.4 micromol/L) was 0.52-nmol/L (95% CI: 0.04, 1.0) lower in HIV-infected women than in uninfected women and 0.65-nmol/L (0.014, 1.28) lower in weeks 25-35 than in weeks 22-25. Serum ferritin (geometric x: 11.6 microg/L) was 0.93 times (0.86, 0.99) lower in HIV-infected women and 2.25 times (1.41, 3.61) higher in women with malaria parasitemia than in uninfected women. Similarly, serum ferritin was 0.71 times (0.63, 0.79) higher in weeks 32-35 than in weeks 22-25 and 1.21 times (1.12, 1.29) higher in gravida > or =3 than in gravida 1. Elevated serum ACT was a strong predictor of serum folate, serum ferritin, and hemoglobin. HIV infection was associated with a 12.9-g/L (8.9, 16.8) lower hemoglobin concentration in women with nondepleted iron stores but low serum retinol and a 7-8-g/L lower hemoglobin concentration in women with other combinations of serum ferritin and retinol (P for interaction = 0.038). Season, age, gestational age, and gravidity were not significant predictors of hemoglobin. Low serum folate, ferritin, and retinol were associated with low hemoglobin. CONCLUSIONS: HIV was associated with lower serum folate, serum ferritin, and hemoglobin. HIV infection was also associated with lower hemoglobin, particularly in women with stored iron and low serum retinol. Low serum folate, ferritin, and retinol were associated with low hemoglobin.

Acute-Phase Reaction↗

Decreased serum insulin-like growth factor-I in burn patients: relationship with serum insulin-like growth factor binding protein-3 proteolysis and the influence of lipid composition in nutritional support.

OBJECTIVES: To test the effects of the amount and type of fat in the nutritional support on serum insulin-like growth factor (IGF)-I concentrations in burn patients and to test the hypothesis that the serum proteolytic activity for insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the decreased serum IGF-I observed in these patients. DESIGN: Randomized, double-blind trial of three different nutritional supports and analysis of serum IGF-I, IGFBP-3, and serum IGFBP-3 proteolysis. SETTING: Burn center in a university hospital. PATIENTS: A total of 23 severely burned (>25% total body surface area burned) adult patients. INTERVENTIONS: Patients were randomly assigned to three types of nutritional support differing in the amount of energy derived from fat and the presence or absence of fish oil: Group I (control), 35% fat; Group II, 15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both parenteral and enteral and was started within 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every 3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3 was measured as well. Serum IGF-I concentration was low in all subjects throughout the study period, but did increase with time (p < .01); significantly higher values were found in Group III (p < .05). Multivariate analysis showed that fish oil and low fat solutions were significantly correlated to serum IGF-I concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal throughout the study with no difference between the groups. Between days 4 and 16, IGFBP-3 was cleaved into two fragments in all patients studied, and the molecular weights of the fragments were equal to those observed in the serum of a woman late in pregnancy. During this period of time, serum proteolytic activity for rhIGFBP-3 was >30% in 24 of the 30 samples measured, whereas 20 of the 28 samples measured thereafter were normal (<25%). Serum IGFBP-3 concentration from ligand binding assay was correlated with serum proteolytic capacity in all subjects (mean r2 = 0.77; p < .01) and with serum IGF-I concentrations in five of six subjects (mean r2 = 0.81; p < .01). CONCLUSIONS: In burn injury, serum IGF-I concentrations are sensitive to the amount and type of fat in their nutritional support. The presence of fish oil allowed for a more rapid recovery of serum IGF-I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased serum IGF-I values and the protease(s) responsible for this seem to be similar to those observed in late pregnancy.

Adult↗

Relationship of serum HER-2/neu and serum CA 15-3 in patients with metastatic breast cancer.

BACKGROUND: Serum HER-2/neu antigen concentrations have been reported to correlate with increased tumor volume in patients with breast cancer. We measured serum CA 15-3, a surrogate marker of disease burden, and correlated serum CA 15-3 with serum HER-2/neu and analyzed the association of both markers with clinical outcomes. METHODS: Pretreatment serum samples from 566 patients were retrospectively analyzed from 2 phase III clinical trials of estrogen receptor-positive (ER(+)), ER(-)/progesterone receptor-positive, or ER status unknown metastatic breast cancer patients randomized in two similar studies to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole). The extracellular domain of the HER-2/neu (c-erbB-2) oncogene and serum CA 15-3 were measured by ELISA on the Bayer Immuno 1. RESULTS: Serum HER-2/neu protein was increased in 168 patients (30%), and CA 15-3 was increased in 337 (60%) patients. Serum CA 15-3 and HER-2/neu were weakly correlated (r = 0.39; P <0.0001). The clinical benefit (complete responses plus partial responses plus stable disease) of endocrine therapy was significantly lower in patients with increased serum HER-2/neu. When adjusted for serum HER-2/neu, serum CA 15-3 was not predictive of response rates. The median time to progression was shorter in patients with increased serum HER-2/neu (89 days) compared with patients with normal serum HER-2/neu (176 days). Survival was significantly shorter in patients with increased serum HER-2/neu (513 vs 869 days; P <0.0001) or increased serum CA 15-3 (689 vs 939 days; P <0.0001). This observation was confirmed by multivariate analysis. CONCLUSIONS: Serum HER-2/neu is a significant independent predictive and prognostic factor in hormone receptor-positive metastatic breast cancer, even when adjusted for tumor burden as measured by CA 15-3. The combination of increased serum HER-2/neu and increased serum CA 15-3 predicts a worse prognosis than does increased CA 15-3 alone.

Adult↗

[Clinical significance of matrix metalloproteinase-9/tissue inhibitors of matrix metalloproteinase -1 imbalance in maternal serum, amniotic fluid, umbilical cord serum in patients with premature rupture of the membranes].

OBJECTIVE: To investigate the roles of matrix metalloproteinase (MMP)-9 and tissue inhibitors of matrix metalloproteinase (TIMP)-1 in maternal serum, amniotic fluid and umbilical cord serum in predicting premature rupture of the membranes (PROM) and chorioamnionitis. METHODS: The levels of MMP-9 and TIMP-1 were detected by enzyme linked immunosorbent assay in maternal serum, amniotic fluid, umbilical cord serum of 58 pregnant women with PROM and 38 women with normal pregnancies. Chorioamnionitis was histopathologically confirmed after delivery. RESULTS: (1) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (141.9 +/- 84.6) ng/L, (138.2 +/- 81.4) ng/L and (85.6 +/- 27.5) ng/L respectively, significantly higher in patients with PROM than those of the control group (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (378.1 +/- 220.2) ng/L, (44.6 +/- 24.0) ng/L and (257.2 +/- 98.8) ng/L respectively, significantly lower in patients with PROM than those of the control group (P < 0.05, P < 0.05 and P < 0.01 respectively). (2) The longer the duration from rupture of membranes to delivery was, the more serious chorioamnionitis was, and the higher the levels of MMP-9 and the lower the TIMP-1 levels in maternal serum, amniotic fluid, and umbilical cord serum were. (3) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (183.8 +/- 84.7) ng/L, (171.2 +/- 92.9) ng/L and (95.5 +/- 21.1) ng/L respectively, significantly higher in patients with chorioamnionitis than those of non-chorioamnionitis (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (269.7 +/- 144.4) ng/L, (32.1 +/- 16.6) ng/L and (210.6 +/- 81.9) ng/L respectively, significantly lower in patients with chorioamnionitis than those of non-chorioamnionitis (P < 0.05, P < 0.05 and P < 0.01 respectively). (4) The levels of MMP-9 in maternal serum, umbilical cord serum and amniotic fluid were (234.4 +/- 79.4) ng/L, (222.1 +/- 120.1) ng/L and (108.5 +/- 42.2) ng/L respectively, significantly higher in neonates whose Apgar score < or = 7 than those of neonates whose Apgar score > or = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively), while the levels of TIMP-1 in maternal serum, amniotic fluid and umbilical cord serum were (225.3 +/- 121.7) ng/L, (25.2 +/- 15.8) and (181.7 +/- 135.2) ng/L respectively, significantly lower in neonates whose Apgar score < or = 7 than those of neonates whose Apgar score > or = 8 (P < 0.05, P < 0.05 and P < 0.01 respectively). CONCLUSIONS: It is suggested that preterm PROM is associated with increased MMP-9 and decreased TIMP-1 levels. MMP-9 and TIMP-1 are valuable clinical biological markers for identifying chorioamnionitis and predicting neonates prognosis.

Adult↗

Comparison of effects of the rise in serum testosterone by raloxifene and oral testosterone on serum insulin-like growth factor-1 and insulin-like growth factor binding protein-3.

OBJECTIVE: In aging men serum levels of testosterone and insulin-like growth factor-1 (IGF-1) decline, potential factors in the reduced muscle strength, abdominal obesity, sexual dysfunction and impaired general well being of aging. The partial oestrogen agonist and antagonist raloxifene increase serum testosterone levels in aging men, but the effect of raloxifene on serum IGF-1 levels in men is unknown. In this study the effects of raloxifene on IGF-1 levels and the associated increase in serum testosterone were compared to the effects of oral testosterone supplementation. DESIGN AND PATIENTS: Thirty healthy elderly men between 60 and 70 years received raloxifene 120 mg/day or placebo in a randomised double blind fashion for 3 months. Secondly, seven female to male (F to M) transsexuals undergoing hormonal sex reassignment received testosterone undecanoate 160 mg/day. MEASUREMENT: At baseline and after three months serum levels of testosterone, IGF-1 and its most important binding protein, IFGBP-3 was measured. In the group transsexuals also serum gonadotrophins and 17beta-oestradiol was measured. RESULTS: Compared to placebo raloxifene increased serum testosterone by 20% but it decreased serum IGF-1 levels by 24.5% (95% confidence interval (CI): -13.0 to -36.1%). No significant change in serum IGFBP-3 levels was found. The effect of raloxifene on serum IGF-1 has been observed with other oral oestrogens, and, therefore, is likely to be ascribed to the partial oestrogen agonist activity of raloxifene. In the F to M transsexuals, serum testosterone levels increased from median <1.0 nmol/l to 6.2 nmol/l, without significant changes in serum gonadotrophins and 17beta-oestradiol levels. Serum IGF-1 levels increased by 12.1% (95% CI: 1.9-22.3%) versus baseline. No effect was observed on serum IGFBP-3 levels. CONCLUSION: Both raloxifene and oral testosterone increased serum testosterone, but raloxifene significantly decreased serum IGF-1 levels without affecting IGFBP-3. By contrast, oral testosterone supplementation in F to M transsexuals increased IGF-1 levels. In both treatment groups no significant change in serum IGFBP-3 was found.

Administration, Oral↗

Monitoring of treatment success in patients with acromegaly: the value of serum insulin-like growth factor binding protein-3 and serum leptin measurements in comparison to plasma insulin-like growth factor I determination.

The aim of the present study was to determine the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) and serum leptin measurements in comparison with plasma insulin-like growth factor I (IGF-I) measurements as indicators of treatment success in patients with acromegaly. Thirty-five acromegaly patients, 25 female and 10 male, divided into groups of patients with postadenomectomy "active" acromegaly (n = 20) and patients with postadenomectomy "controlled" acromegaly (n = 15), and 44 healthy volunteers sex- and age-matched with the acromegaly patients were included in the present study. We comparatively analyzed plasma IGF-I, serum IGFBP-3, and serum leptin levels in the aforementioned groups. Because serum leptin has sex dimorphism, the groups were divided into sexes when leptin was evaluated. As expected, the patients with active acromegaly had significantly higher mean values of plasma IGF-I and serum IGFBP-3 and lower mean values of serum leptin (only in women) than the control group. However, individual evaluation showed that 1 of 20, 9 of 20, and many patients with postadenomectomy active acromegaly patients had values that overlapped values of control subjects for plasma standard deviation score (SDS)-IGF-I, serum SDS-IGFBP-3, and sex-adjusted serum leptin, respectively. Application of the receiver operating characteristic (ROC) curves method shows that plasma IGF-I measurement has the best discriminatory power to differentiate patients with postsurgical active acromegaly from healthy people. Its area under the curve (AUC) was 0.95, with a sensitivity and specificity of 86% and 94%, respectively. Its positive and negative likelihood ratios were 14 and 0.15. Serum IGFBP-3 has certain discriminatory power, its AUC being 0.89, with a sensitivity and specificity of 83% and 77%. Its positive and negative likelihood ratios were 3.6 and 0.22. Serum leptin, both in women and in men, has a poor performance with sensitivity and specificity of 53% and 50% for women and 55% and 56% for men and positive and negative likelihood ratios of 1.06 and 0.94 for women and 1.26 and 0.8 for men. Application of the ROC curves method and the determination of positive and negative likelihood ratios in comparative evaluation of serum IGFBP-3 and serum leptin with plasma IGF-I as indicators of treatment success in acromegalic patients showed that neither serum IGFBP-3 nor serum leptin determinations have accuracy better than or similar to that of plasma IGF-I for monitoring treatment success in acromegaly patients. Serum IGFBP-3 is accurate but does not increase accuracy for age-adjusted plasma IGF-I, whereas determination of serum leptin level has no value in monitoring these patients.

Acromegaly↗

Dissociation of the early decline in serum T(3) concentration and serum IL-6 rise and TNFalpha in nonthyroidal illness syndrome induced by abdominal surgery.

The etiology of the prompt decline in serum T(3) in patients with nonthyroidal illness syndrome has not been adequately explained. It has been attributed to various parameters, including test artifacts, inhibitors of T(4) and T(3) binding to proteins, decreased 5'-deiodinase activity, and circulating cytokines. Currently, much attention is centered on the role of IL-6 and TNFalpha in developing the nonthyroidal illness syndrome through an effect on the hypothalamus, pituitary, and possibly 5'-deiodinase activity. We therefore studied the relation of the endogenous serum IL-6 and TNFalpha rise early in the course of nonthyroidal illness syndrome to the early decline in serum T(3) in 19 apparently healthy individuals, aged 43 +/- 16 yr, who underwent elective abdominal surgery for cholelithiasis or gastroplasty. Serum T(3), free T(3), T(4), free T(4), rT(3), TSH, IL-6, and TNFalpha were measured before and at various time intervals up to 42 h after skin incision. We observed a prompt decline in serum T(3) 30 min before skin incision, which continued to decline throughout the observational period. The magnitude of the decline reached 20% from the baseline value at 2 h. The early decline of T(3) was attenuated and lasted from the 2-8 h, probably due to the sharp increase in serum TSH that started immediately after the entrance to the operating room and lasted for 2 h. In contrast, serum T(4) and free T(4) concentrations were increased soon after skin incision and remained elevated during the first postoperative day. Serum rT(3) increased approximately 6 h after the initiation of surgery and remained elevated thereafter. Serum IL-6 remained essentially undetectable for 2 h after skin incision, whereas serum T(3) was low. Two hours after skin incision, serum IL-6 increased sharply and remained elevated throughout the observational period. Serum TNFalpha remained essentially undetectable throughout the postoperative period. Serum cortisol increased rapidly upon entrance to the operating room and remained elevated throughout the postoperative period. We conclude that the decline in serum T(3) early in the course of nonthyroidal illness syndrome is not due to increased serum IL-6 or TNFalpha levels. The brisk TSH secretion soon after the onset of the syndrome attenuates the decline in serum T(3) due to T(3) secretion from the thyroid. The early and brisk cortisol response to surgery may at least in part explain the early decrease in serum T(3) in nonthyroidal illness syndrome.

Abdomen↗

Serum uric acid concentrations in type 2 diabetes: its significant relationship to serum 1,5-anhydroglucitol concentrations.

OBJECTIVE: Serum uric acid concentrations in diabetics are well known to be significantly lower than those in non-diabetic subjects, due to increased its urinary clearance. Serum 1,5-anhydroglucitol concentrations are also specifically decreased in diabetics through the increased urinary excretion. To gain an insight into the idea that a common mechanism might be possible to work in reducing these serum substances, this study was conducted. METHODS: A total of 121 type 2 diabetic patients, 76 males and 45 females, were studied. Multiple regression analysis was performed to determine the independent association between potential predictor variables (mean blood pressure, body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, serum fructosamine, serum 1,5-anhydroglucitol, serum creatinine, serum total cholesterol, and serum triglycerides) and serum uric acid concentrations as the dependent variable. RESULTS: In the male subjects, serum 1,5-anhydroglucitol, serum creatinine and body mass index were the variables independently related to serum uric acid concentrations. In the female subjects, serum 1,5-anhydroglucitol and serum creatinine were the variables independently related to serum uric acid concentrations. CONCLUSION: Considering the glucosuria-related urinary excretion of 1,5-anhydroglucitol, a close positive association between serum uric acid and 1,5-anhydroglucitol concentrations strongly supports the idea that the reduction in serum uric acid concentrations is mediated by urinary glucose excretion in diabetics.

Adult↗

Serum stimulation of fibronectin gene expression appears to result from rapid serum-induced binding of nuclear proteins to a cAMP response element.

Fibronectin (FN) mRNA levels increased when quiescent cells (serum starved) were stimulated to undergo the G0/G1 transition by the addition of 20% given fetal calf serum to the media. The 5'-flanking region of the FN gene (position +69 to -510 base pairs (bp] was fused to the coding region of the chloramphenicol acetyltransferase (CAT), and the fusion gene was used in transfection assays. Expression of FNCAT increased on serum treatment indicating that the region of the FN gene between positions +69 and -510 bp mediated serum responsiveness. Deletion of FN gene 5'-flanking sequences from position -510 to -122 bp eliminated serum responsiveness suggesting that an element between these positions was mediating the effect. Sequences between positions -122 and -510 bp of the FN gene were able to confer serum responsiveness on a herpes virus thymidine kinase promoter-CAT fusion gene (TKCAT) when the FN gene sequences were cloned upstream of TKCAT. The ability to confer serum responsiveness on TKCAT was retained with a smaller 100-bp sequence (position -122 to -222 bp). Both a cAMP response element (position -170 bp) and a nuclear factor-1 binding site (position -155 bp) have been identified within this sequence (Dean, D. C., Blakeley, M. S., Newby, R. F., Ghazal, P., Hennighausen, L., and Bourgeois, S. (1989) Mol. Cell. Biol. 9, 1498-1506). The cAMP response element was serum-responsive when cloned upstream of TKCAT or a minimal FN promoter (deleted to position -56 bp) while the nuclear factor-1 binding site was unresponsive. Therefore, the cAMP regulatory element (CRE) is the serum-responsive element between position -122 and -222 bp. Serum-induced binding of proteins to the CRE was detected in gel retardation assays with extracts from cell lines where FN expression was serum-responsive. However, no serum-induced binding was detected with extracts from the JEG-3 cell line where FN expression was not serum-responsive. Serum-induced binding occurred rapidly, within 15 min, and did not require protein synthesis. The decay of serum-induced binding was relatively slow as increased binding was still detectable 24 h after removal of serum. The CRE also mediates transcriptional stimulation by cAMP, but unlike serum stimulation increased CRE binding activity was not detectable in extracts from cAMP-treated cells (Dean, D. C., Blakeley, M. S., Newby, R. F., Ghazal, P., Hennighausen, L., and Bourgeois, S. (1989) Mol. Cell. Biol. 9, 1498-1506).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗