Transforming growth factor ß1 genotypes in relation to TGFß1, interleukin-8, and tumor necrosis factor alpha in induced sputum and blood in cystic fibrosis.

BACKGROUND: High-producer TGFß1 genotypes are associated with severe lung disease in cystic fibrosis (CF), but studies combining IL-8, TNFα-, and TGFß1(+genotype) levels and their impact on CF lung disease are scarce. AIM: Assessing the relationship between TGF ß 1, IL-8, and TNF- α and lung disease in CF in an exacerbation-free interval. METHODS: Twenty four patients delta F508 homozygous (median age 20.5 y, Shwachman score 75, FEV1(%) 83) and 8 controls (median age 27.5 y) were examined. TGF ß 1 was assessed in serum and induced sputum (IS) by ELISA, for IL-8 and TNF- α by chemiluminescence in IS and whole blood. Genotyping was performed for TGF ß 1 C-509T and T+869C utilizing RFLP. RESULTS: TGF ß 1 in IS (CF/controls median 76.5/59.1 pg/mL, P < 0.074) was higher in CF. There was a negative correlation between TGF ß 1 in serum and lung function (LF) (FEV1 (r = -0.488, P = 0.025), MEF 25 (r = -0.425, P = 0.055), and VC (r = -0.572, P = 0.007)). Genotypes had no impact on TGF ß 1 in IS, serum, and LF. In IS TGF ß 1 correlated with IL-8 (r = 0.593, P < 0.007) and TNF- α (r = 0.536, P < 0.018) in patients colonized by bacteria with flagellin. CONCLUSION: TGF ß 1 in serum not in IS correlates with LF. In patients colonized by bacteria with flagellin, TGF ß 1 correlates with IL-8 and TNF- α in IS.

TCF7L2 polymorphism rs7903146 and predisposition for type 2 diabetes mellitus in obese children.

Polymorphism RS7903146 in transcription factor 7-like2 gene ( TCF7L2) is associated with type 2-diabetes mellitus (T2DM) in adults. Concerned with predisposition for diabetes mellitus in obese children, we tested if risk genotypes TC and TT of rs7903146 are more common in obese children with increased homeostasis model assessment insulin resistance index (HOMA-IR) compared to obese controls with normal HOMA-IR. As exploratory analysis, we also calculated beta-cell function for these risk genotypes and measured glucagon-like peptide 1 (GLP-1) in a subgroup. The cohort was 401 obese children (BMI > 2SDS; 211 female; 59% presenting increased HOMA-IR) from two German outpatient obesity referral centers. Genotype distributions in patients presenting increased HOMA-IR (TT: 10.18%, CT: 35.65%, CC: 54.17%) and in patients with normal HOMA-IR (TT: 8.66%, CT: 42.67%, CC: 48.67%) provided no significant effect of these two risk genotypes (p > 0.2). Correction for possible confounder's gender, age, pubertal stage, and BMI revealed no association with glucose metabolism parameters including GLP-1. However, exploratory HOMA-B% index was comparatively higher in TT-homozygotes (p=0.021) as compared to CC-homozygotes. We conclude that even though TT and CT genotypes were not higher in patients presenting elevated HOMA-IR, the higher HOMA-B% index in TT-homozygotes indicates TCF7L2 to be a susceptibility gene for the development of impaired glucose tolerance in obese children as demonstrated in several adult cohort studies.

Predictive value of thyroglobulin changes for the efficacy of thyroid remnant ablation.

The aim of this case-control study was to determine the utility of the evaluation of changes in serum thyroglobulin (Tg) levels before and after 1311 diagnostic total body scan (TBS) in patients with thyroid cancer to predict the efficacy of radioiodine ablation. Among 134 consecutive patients with differentiated thyroid carcinoma (DTC) who had undergone a thyroidectomy and TBS prior to radioiodine ablation, we selected those subjects with no evidence of distant metastases and with two consecutive assessments of Tg before TBS and radioiodine ablation within a period of four weeks. With this selection procedure 27 patients (22 with papillary and five with follicular carcinomas) were included in our evaluation. The ablation therapy was considered successful when the TBS performed one year after treatment did not show any or less than 1% cervical 131I uptake, Tg levels remained below 3 ng/mL, and clinical and instrumental examinations were negative for the presence of relapses. These criteria divided the selected patients into two subsets: patients with successful radioiodine ablation and patients with residual thyroid tissue. The majority of patients with unsuccessful ablation showed an increase in serum Tg levels, while most of the patients with successful ablation showed a steady decrease in Tg concentrations. Statistical analysis evidenced that the increase in Tg levels after TBS was related to unsuccessful ablation (P > or = 0.01). By contrast, the rate of thyroid remnants with 131I uptake did not show any relationship with the outcome of ablation therapy. The group of patients with increasing Tg levels after TBS had a relative risk of 3.3 of unsuccessful ablative therapy compared to the group with stable or decreasing Tg levels. This study supports the concept that by monitoring Tg levels in patients who undergo diagnostic TBS before radioiodine ablation it is possible to obtain useful information about the efficacy of 131I therapy.

Nuclear medicine procedures in lung cancer.

Although radiography, computed tomography and magnetic resonance imaging are still the methods of choice for the study of lung cancer, they have certain limitations in the determination of the nature of suspicious lung nodules, the evaluation of mediastinal involvement, the assessment of the viability of previously treated lesions and the diagnosis of tumour relapse. There is a wide range of current oncological requirements related to lung cancer: detection of malignant lesions at the earliest stage and in the most effective way; the definition of the biological characteristics of a lesion (proliferation, aggressiveness, differentiation, etc.); the need to define the operability of the patient (function of residual lung and staging); and the need to evaluate the behaviour of the tumour (response to therapy, early detection of recurrences, metastatic spread). Most of the efforts of the nuclear medicine community have been focussed on diagnosis, staging, restaging and therapy monitoring of lung cancer. Many radiopharmaceuticals have been employed for this, including gallium, monoclonal antibodies, somatostatin analogues, lipophilic cations and positron emission tracers. There is ample evidence that nuclear medicine techniques may provide complementary information with respect to anatomical imaging, for example in the assessment of preoperative function by means of ventilation and perfusion scintigraphy, or in tumour localisation by means of specific tumour-seeking agents. However, clinical data suggest that, when properly used, nuclear medicine procedures in some cases may be not only complementary to radiology but essential for the clinical management of lung cancer. An example of such a procedure is fluorodeoxyglucose positron emission tomography (FDG PET) the introduction of which has greatly contributed to confirmation of the clinical value of nuclear medicine in this field. FDG PET has proved of great help in lung cancer management and its cost-effectiveness in lung cancer staging is firmly established. In this review the results of the most important nuclear medicine techniques are summarised and their value in clinical practice is discussed. General, updated information is provided about the epidemiology, biology and clinical management of lung cancer, and about the role of nuclear medicine in these areas.

Absence of renal 25-hydroxycholecalciferol-1-hydroxylase activity in a pig strain with vitamin D-dependent rickets.

Cholecalciferol-1-hydroxylase activities were estimated in renal cortex homogenates and mitochondrial preparations from three groups of 6- to 12-week-old pigs. Five animals suffering from an inherited form of vitamin D-deficiency rickets showed symptoms of florid rickets when used for this study. Six pigs were normocalcemic heterozygous litter mates of the rachitic strain and three pigs were normal controls (German land-race and wild pigs). The renal cortex homogenates and mitochondrial preparations were incubated for 5-30 min at 37 degrees C with 25-(26-27-methyl-3H) OHD3 as substrate. 1,25(OH)2D3 was subsequently identified in normal phase (Zorbax-Sil) and reversed phase (Zorbax-ODS) HPLC eluates. 1-hydroxylase activities were demonstrated in both normal controls and heterozygote offspring and were ten times above minimum detectability of the assay. The km was 255 +/- 74 (SD) and 278 +/- 85 nmol X 1(-1) in controls and heterozygote offspring, respectively. The Vmax in the two groups was between 0.11 and 0.794 and decreased with age of the animals. Km and Vmax did not differ between the two groups. In homozygous, hypocalcemic rachitic animals no 1-hydroxylase activity was detectable in either homogenates or mitochondrial preparations. Addition of kidney homogenate from a rachitic animal to a homogenate from a normal pig did not specifically depress 1-hydroxylase activity in the mixture. Treatment of rachitic pigs with 1.0 microgram/day of 1,25(OH)2D3 for 4 weeks also had no effect on 1-hydroxylase activity. It is concluded that the rachitic pigs suffer from an inborn error of renal 1,25(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS)

A low-temperature thermal process for the decomposition of water.

The following three reactions, each of which has been shown to proceed at the temperature indicated above the arrow, are suggested as a cycle for the thermal decomposition of water: