The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study

In men, hypoandrogenism is associated with features of the metabolic syndrome. It is not known whether men with the metabolic syndrome are at a higher risk of developing hypogonadism. We therefore assessed whether the metabolic syndrome predicts development of hypogonadism 11 yr later in 651 middle-aged Finnish men participating in a population-based cohort study. Men with the metabolic syndrome at baseline as defined by the World Health Organization (n = 114, 20%) had a 2.6-fold increased risk of developing hypogonadism as defined by total testosterone levels less than 11 nmol/liter at the 11-yr follow-up independent of age, smoking, and other potential confounders. Further adjustment for body mass index (OR, 2.0; 95% CI, 1.1-3.8) or baseline total testosterone levels (OR, 1.9; 95% CI, 1.0-3.4) attenuated the association. The association of the metabolic syndrome with hypogonadism as defined by calculated free testosterone levels less than 225 pmol/liter was similar, but weaker. The adjusted decrease in testosterone concentrations during the 11-yr follow-up was also greater in men with than without the metabolic syndrome. Smokers had a nonsignificantly lower risk of developing hypogonadism during follow-up, whereas a decrease in smoking increased the risk of hypogonadism. The metabolic syndrome predisposes to development of hypogonadism in middle-aged men. Prevention of abdominal obesity and the accompanying metabolic syndrome in middle age may decrease the risk of hypogonadism in men, especially in those who quit smoking.     

Activin inhibition limits early innate immune response in rat kidney allografts—a pilot study

Activins are members of the transforming growth factor‐beta (TGF‐β) superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. The study was carried out in kidney transplantation and renal ischemia‐reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB‐Fc) was used to inhibit activin signaling. Transplantation groups were as follows: (i) cyclosporine A (CsA) (ii) CsA + sActRIIB‐Fc, (iii) CsA+ inactive protein control Fc‐G1. IRI groups were as follows: (i) no treatment, (ii) sActRIIB‐Fc. Serum activin B concentration was significantly elevated after transplantation and IRI, whereas activin A was produced locally in renal allografts. Activin inhibition efficiently limited neutrophil, macrophage, and dendritic cell infiltration to the allografts measured 72 h after transplantation. In addition, sActRIIB‐Fc treatment modulated serum cytokine response after transplantation and reduced the early accumulation of fibroblasts in the graft interstitium. In conclusion activin inhibition reduces the innate immune response early after renal transplantation in the rat. It also limits the accumulation of fibroblasts in the graft suggesting that activins may be involved in the fibrogenic signaling already early after kidney transplantation.     

Factors affecting bone loss around menopause in women without HRT: a prospective study

OBJECTIVES: The present study evaluated the effects of menopause and other putative bone loss modifying factors on bone mineral density (BMD) change. METHODS: The study population, 396 healthy women aged 48-59 years with no history of hormone replacement therapy (HRT) use or any bone affecting disease or medications, was selected from a random sample (n=2025) of the OSTPRE-study cohort (n=13100) in Kuopio, Finland. BMD at lumbar spine (LS) and three areas of proximal femur (femoral neck (FN), Ward's triangle (W), trochanter (T)) was measured with dual X-ray absorptiometry at baseline in 1989-1991 and at 5 years in 1994-1997. RESULTS: 116 women who reported the beginning of menopause during the follow-up (perimenopausal) had the greatest mean annual bone loss (-1.22%/year (LS), -0.87% year (FN), -1.14%/year (W), -0.36%/year (T)). In women under 5 years postmenopausal at baseline (early postmenopausal, n=172) bone loss rate was significantly lower than in perimenopausal women. In women over 5 years postmenopausal at baseline (late postmenopausal, n=108) bone loss rate was significantly further decreased only at lumbar spine. In peri- and postmenopausal women the annual BMD change was best described as a trinomial function of the duration of menopause at all sites (P<0.03). Of the life-style factors studied protective effects were found in weight increase in both spinal and femoral bone (P=0.010/P<0.001), high baseline weight in spine (P<0.001) and high grip strength in femoral neck (P=0.002). CONCLUSION: The beginning of menopause is accompanied by significant bone loss, which decreases in later menopause. Few other physiological and life-style factors were found to significantly contribute to this phenomenon.     

Kinetics and avidity of antibodies evoked by heptavalent pneumococcal conjugate vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.     

Hormone response of diabetic patients to exercise at cool and warm temperatures

Summary Both exercise and high ambient temperatures stimulate the secretion of counterregulatory hormones which can change glucose homeostasis. We studied whether in diabetic patients there are any differences in the hormonal response to exercise performed at cool or warm ambient temperatures. A study was performed on eight male insulin-dependent patients at rest and during exercise at + 10° C and + 30° C. Exercise consisted of three consecutive 15-min periods at 60% of maximal aerobic capacity. The concentrations of plasma lactate and counterregulatory hormones at rest were similar at warm and cool temperature, whereas prolactin concentration was higher (P < 0.01) at +30° C. Exercise resulted in an increase in noradrenaline, growth hormone and prolactin (P < 0.01), prevented the diurnal decrease in cortisol, but had no effect on glucagon. Hormone responses to exercise were similar at + 10° C and at +30°C, except for cortisol and noradrenaline which showed greater responses at warm than at cool temperatures. This may have been due to the higher relative work load at warm compared to cool temperatures as suggested by the higher heart rate and greater increase of lactate at +30° C. These data indicate that within a range of ambient temperatures commonly occurring in sports, the response of counterregulatory hormones is largely independent of ambient temperature in insulin-dependent diabetic patients.     

Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated by a surface-associated carbohydrate-degrading enzyme,pullulanase

The interactions between pathogenic bacteria and the host need to be resolved at the molecular level in order to develop novel antiadhesive drugs and vaccines. We have previously identified strepadhesin, a novel glycoprotein-binding activity in Streptococcus pyogenes binding to thyroglobulin, submaxillar mucin, fetuin, and asialofetuin. The activity is known to be regulated by Mga, a regulator of streptococcal virulence factors, and is carried by the surface-associated streptococcal cysteine protease, SpeB. In the present study, we focused on the high strepadhesin activity in an S. pyogenes strain (NZ131rgg) lacking SpeB expression. By extracting surface proteins from the bacteria, a new strepadhesin protein was identified, and mass spectrometric analysis and database search identified it as a putative pullulanase. The gene was cloned, and the recombinant pullulanase (PulA) exhibited pullulanase and starch hydrolyzing activity, as well as strepadhesin activity. Sequencing of the pulA gene revealed an open reading frame with 3,498 bp encoding a protein of 1,165 amino acids with a predicted molecular mass of 129 kDa. PulA exhibited properties typical for a gram-positive surface protein with a putative signal sequence and LPKTGE cell wall anchoring motif and contained the four highly conserved regions common to pullulanases. Mutant bacteria deficient in PulA expression showed diminished strepadhesin activity on bacterial dot blot assay and reduced adherence to thyroglobulin immobilized on microtiter plates. Thus, S. pyogenes strepadhesin activity is carried by a surface-bound pullulanase, which combines glycoprotein-binding and carbohydrate-degrading activities in the same molecule.     

Metabolic changes induced by combined prolonged exercise and low-calorie intake in man

Summary Thirteen middle-aged women and 10 men walked 344 km during 7 days. The daily walking distances were 57, 53, 67, 53, 41, 36, and 37 km at an average speed of 3.5 km·h^–1. During the hike the subjects drank water, mineral drinks, and juices ad libitum. Except for some natural products, no food intake was allowed. During the hike the body weight and serum protein concentration of the subjects decreased by about 7%, on average. Serum triglyceride and total cholesterol decreased drastically, about 30–40% during the hike, but HDL-cholesterol showed a tendency to increase, giving a 40% increment in HDL/total cholesterol ratio. Serum free fatty acids rose 1.5–2 times above the starting level. Serum glucose and evening insulin levels decreased significantly during the hike. Serum cortisol in evening samples after the daily walking and plasma norepinephrine concentrations were significantly increased, reflecting the immediate daily response to the combined fasting and walking. Serum testosterone levels decreased in men but not in women, indicating the involvement of the LH-testis pathway in the decrease obtained. Serum ASAT activity rose to about three times the starting level during the hike, whereas -GT activity gradually decreased. These marked metabolic changes caused by combined fasting and several days exercise were in many respects (as in cholesterol, HDL/total cholesterol ratio or testosterone levels) more pronounced than those earlier reported to be caused by exercise or fasting alone.     

Activation Dynamics in Anisotropic Cardiac Tissue via Decoupling

Bidomain theory for cardiac tissue assumes two interpenetrating anisotropic media--intracellular (i) and extracellular (e)--connected everywhere via a cell membrane; four local parameters sigma(i,e)(l,t) specify conductivities in the longitudinal (l) and transverse (t) directions with respect to cardiac muscle fibers. The full bidomain model for the propagation of electrical activation consists of coupled elliptic-parabolic partial differential equations for the transmembrane potential upsilon(m) and extracellular potential phi(e), together with quasistatic equations for the flow of current in the extracardiac regions. In this work we develop a preliminary assessment of the consequences of neglecting the effect of the passive extracardiac tissue and intracardiac blood masses on wave propagation in isolated whole heart models and describe a decoupling procedure, which requires no assumptions on the anisotropic conductivities and which yields a single reaction-diffusion equation for simulating the propagation of activation. This reduction to a decoupled model is justified in terms of the dimensionless parameter epsilon = (sigma(i)(l)sigma(e)(t) - sigma(i)(t)sigma(e)(l))/(sigma(i)(l) + sigma(e)(l))(sigma(i)(t) + sigma(e)(t)). Numerical simulations are generated which compare propagation in a sheet H of cardiac tissue using the full bidomain model, an isolated bidomain model, and the decoupled model. Preliminary results suggest that the decoupled model may be adequate for studying general properties of cardiac dynamics in isolated whole heart models.     

Simulated Epicardial Potential Maps During Paced Activation Reflect Myocardial Fibrous Structure

Using a three-dimensional propagation model of the human ventricular myocardium, we studied the role of fibrous structure in generating epicardial potential maps. This model represents the myocardium as an anisotropic bidomain with an equal anisotropy ratio, and it incorporates a realistic representation of anatomical features, including epi-endocardial fiber rotation in the compact portion of the wall (compacta) and a distinct fiber arrangement of the trabeculated portion (trabeculata). Activation sequences were elicited at various intramural depths, and maps were calculated throughout a 60 ms sequence. The simulated maps closely resembled those measured by others in the canine heart. During the early stages of activation, a typical map featuring a central minimum flanked by two maxima emerged, with the axis joining these extrema approximately parallel to the fibers near the pacing site, and the axis joining the maxima rotated in the same direction as the fibers for different pacing depths; for endocardial and subendocardial pacing this map changed into one with an oblong positive area. During the later stages of activation, the positive areas of the maps expanded and rotated with the transmural fiber rotation. In concurrence with experiments, we saw a fragmentation and asymmetry of expanding and rotating positive areas. The latter features—apparently caused by the interface between the compacta and trabeculata, variable local thickness of the wall, or local undulations of the vetricular surface—could not be reproduced by more idealized, slab models. © 1998 Biomedical Engineering Society. PAC98: 8722-q, 8710+e