Elevated levels of IL-18 in plasma and skeletal muscle in chronic obstructive pulmonary disease.

The aim of this study was to test the hypothesis that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is accompanied by enhanced interleukin 18 (IL-18) expression in skeletal muscle, which may precede muscle weight loss. Twenty patients with moderate to severe COPD [12 women, 66 +/- 9.4 years of age and forced expiratory volume in 1 second (FEV(1)) of 32% +/- 12 % of predicted value] and 20 healthy age-, gender-, and body mass index (BMI)-matched controls (10 nonsymptomatic smokers and 10 nonsmokers) were included in the study. Plasma levels of IL-18 were elevated in COPD patients (n = 20) versus healthy controls (n = 20) (221.2 pg/ml [196.0-294.2 pg/pl] vs. 164.8 pg/ml [144.4-193.3 pg/pl], p = 0.05) [corrected] and IL-18 was expressed in skeletal muscle, with IL-18 mRNA levels being elevated in biopsies from COPD patients (n = 19) versus healthy controls (n = 18) (4.3 [2.6-5.9] vs. 2.4 [1.6-3.1], p = 0.05) [corrected]. Immunohistochemical evaluation revealed a strong expression of IL-18 in Type II muscle fibers from COPD patients. Plasma levels and skeletal muscle mRNA levels of tumor necrosis factor alpha (TNF-alpha) and IL-6 did not differ between the groups. Elevated skeletal muscle expression of IL-18 was found in COPD patients with normal body weight, indicating that IL-18 potentially may be involved in the pathogenesis of COPD-associated muscle wasting.

Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls.

To investigate whether an impaired Leydig cell function is present in severely oligospermic men, serum testosterone (T), LH, estradiol (E(2)), and SHBG levels in 357 idiopathic infertile men were compared with levels in 318 proven fertile men. In addition, the T/LH ratio, E(2)/T ratio, and calculated free T index (cFT) were compared between the two groups.A shift toward lower serum T levels, cFT, and T/LH ratio and higher serum LH, E(2), and E(2)/T levels was observed in the group of infertile men. On average, the infertile men had 18, 26, and 34% lower serum T, cFT, and T/LH levels, respectively, and 19, 18, and 33% higher serum LH, E(2), and E(2)/T levels, respectively, than the fertile men. Twelve percent of the infertile men had a serum T level that fell below the 2.5 percentile of the fertile levels, and 15% of the infertile men had a LH level that was above the 97.5 percentile of the fertile levels.Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous epithelium and the Leydig cells, triggered by distorted function of the seminiferous epithelium. On the other hand, the parallel impairment of spermatogenesis and Leydig cells may reflect a congenital dysfunction of both compartments caused by a testicular dysgenesis during fetal/infant development.

Double-blind Y chromosome microdeletion analysis in men with known sperm parameters and reproductive hormone profiles: microdeletions are specific for spermatogenic failure.

Y chromosome microdeletions have been reported as a possible genetic factor of male infertility. Despite a large number of studies in this subject, there is still considerable debate and confusion surrounding the role of Y chromosome microdeletions in male infertility. This has been further compounded by observations of Y microdeletions in fertile males. The aim of the present study was to evaluate: 1) the incidence of Y microdeletions in control male population and infertile males, where complete semen and hormonal analysis was available to define whether Y microdeletions are specific for spermatogenic failure or if they can be found also in normospermic men; and 2) whether the suboptimal semen quality reported in Denmark is associated with a higher incidence of Y microdeletions in respect to other populations. Double-blind molecular study of deletions was performed in 138 consecutive patients seeking intracytoplasmic sperm injection treatment, 100 men of known fertility, and 107 young military conscripts from the general Danish population. Microdeletions or gene-specific deletions were not detected in normospermic subjects or in subfertile men with a sperm count of more than 1 x 10(6)/mL. Deletions of the Azoospermia factor (AZF)c region were detected in 17% of individuals with idiopathic azoo/cryptozoospermia and in 7% of individuals with nonidiopathic azoo/cryptozoospermia. The data indicate that: 1) the composition of the study population is the major factor in determining deletion frequency; 2) Y chromosome microdeletions are specifically associated with severe spermatogenic failure; therefore, the protocol described here is reliable for the routine clinical workup of severe male factor infertility; and 3) the frequency of Yq microdeletions in the Danish population is similar to that from other countries and argues against the involvement of microdeletions in the relatively low sperm count of the Danish population.