Muscle insulin-like growth factor status, body composition, and functional capacity in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients. METHODS: Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-alpha (TNF-alpha) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting. RESULTS: Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 +/- 0.9 versus 21.5 +/- 1.5 kg, P < .05), as were all measures of functional capacity (P < .01 to .001), and highly significant positive correlations between appendicular lean mass and functional capacity were evident (appendicular lean mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test, all P < .001). TNF-alpha and TNFR1 were elevated in patients (P < .001). Although serum IGF-I and IGFBP-3 levels did not differ between the groups (P = .295 and .379 respectively), fragmented IGFBP-3 levels were increased (53.1 +/- 16.0 versus 29.81 +/- 15.3%, P < .005). In contrast, muscle IGF-I was substantially diminished in the patient group (n = 7) relative to control (n = 5) levels (0.84 +/- 0.06 versus 2.78 +/- 1.80 pg/microg, P < .05). CONCLUSIONS: We provide evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal factor in the muscle wasting characteristic of this population. Future research should determine the exact consequences and causes of alterations to the muscle IGF system in HD patients.     

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.     

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.     

Antibody isotypes to a Paracoccidioides brasiliensis somatic antigen in sub-acute and chronic form paracoccidioidomycosis

This report describes the differences in isotype antibody reactivity against a crude Paracoccidioides brasiliensis antigenic preparation in the sub-acute (SAF) and chronic (CF) forms of paracoccidioidomycosis before treatment. IgG antibodies were detected in all patients, with a slightly but not significantly higher reactivity in the SAF. IgG1 antibodies were present, frequently at high levels, in both forms, whereas IgG3 was always low or absent. IgG2 antibodies were detectable in most patients, but at high levels in only a few CF patients. IgG4 was found mainly in SAF patients, whereas IgA was detected almost only in CF patients, probably due to a Th2 pattern of immune response in the more severe SAF, and the characteristic mucosal involvement of the CF, respectively. Immunoblot analysis showed that, in addition to the 43-kDa immunodominant fraction, other less well-characterised fractions were also recognised differentially by the isotypes and deserve further investigation.     

Plasma protein haptoglobin modulates renal iron loading

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.     

Cross-reactivity among five major pollen allergens

We have studied the cross-reactivity between L. perenne, S. cereale, P. pratense, C. dactylon, and Ph. communis. The results obtained demonstrate that L. perenne, S. cereale, and P. pratense have strong cross-reactivity. C. dactylon has a number of allergens that cross-react with the rest of the grasses studied but they are minor allergens. Ph. communis possesses a moderate cross-reactivity with the species of the group but it has, as well, individual allergens.