Osteoporosis: An Age-Related and Gender-Specific Disease – A Mini-Review

Osteoporosis, a classical age-related disease and known to be more common in women than in men, has been reported increasingly often in men during the past few years. Although men at all ages after puberty have larger bones than women, resulting in greater bending strength, mortality after a hip fracture, one of the major complications of osteoporosis, is more common in men than in women. Sex hormone deficiency is associated with unrestrained osteoclast activity and bone loss. Even though estrogen deficiency is more pronounced in women, it appears to be a major factor in the pathogenesis of osteoporosis in both genders. In contrast to osteoporosis in postmenopausal women, the treatment of osteoporosis in men has been scarcely reported. Nevertheless, some drugs commonly used for the treatment of osteoporosis in women also appear to be effective in men. The aim of this study is to review primary osteoporosis in the elderly with particular emphasis on gender-related aspects.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model

Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg-1 body weight to study acute effects or using daily doses of 10 μg cereulide kg-1 body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations

Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study

Heart failure following acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell (PBMC) suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC) were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and echocardiography were used to quantitate cardiac function. Analysis of soluble factors present in APOSEC was performed by enzyme-linked immunosorbent assay (ELISA) and activation of signalling cascades in human cardiomyocytes by APOSEC in vitro was studied by immunoblot analysis. Intravenous administration of a single dose of APOSEC resulted in a reduction of scar tissue formation in both AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of ejection fraction (57.0 vs. 40.5%, p < 0.01), a better cardiac output (4.0 vs. 2.4 l/min, p < 0.001) and a reduced extent of infarction size (12.6 vs. 6.9%, p < 0.02) as determined by MRI. Exposure of primary human cardiac myocytes with APOSEC in vitro triggered the activation of pro-survival signalling-cascades (AKT, Erk1/2, CREB, c-Jun), increased anti-apoptotic gene products (Bcl-2, BAG1) and protected them from starvation-induced cell death. Intravenous infusion of culture supernatant of apoptotic PBMC attenuates myocardial remodelling in experimental AMI models. This effect is probably due to the activation of pro-survival signalling cascades in the affected cardiomyocytes

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation

Clinical Efficacy of Two Novel, Differentially Administered (IM, ID) Vaccines against <i>Mycoplasma hyopneumoniae</i> and PCV2 in Swine under Field Conditions

Enzootic pneumonia (EP) of pigs is caused by Mycoplasma hyopneumoniae (M.hp.), which is, together with the porcine circovirus type 2 (PCV2), among the most prominent inducers of the porcine respiratory disease complex (PRDC). Therefore, vaccination of piglets against M.hp. and PCV2 is crucial in the fight against pulmonary infections. In this field study, we tested the clinical efficacy of two novel vaccines, one delivered IM (Hyogen® + Circovac®) and the other ID (MHyo-Sphere®PCV ID), on a fattening farm in Lower Austria with a history of still ongoing EP. Average daily weight gain, coughing/sneezing index, losses due to morbidity/mortality, and lung scoring data at slaughter by means of CLP (Ceva Lung Program) were recorded for three consecutive fattening cohorts to achieve a powerful number of animals, one half each vaccinated with the IM vaccine and the other half with the ID vaccine (n = 659 in total). No statistically significant differences could be observed between the two vaccination groups for the parameters investigated, but the total median EP score, which categorizes pulmonary lesions due to infection by M.hp. with a theoretical range of 0–28, was lowered from initially 1.9 to 1.0, indicating that both vaccines proved very suitable measures in the fight against EP

Clinical efficacy of two vaccination strategies against Mycoplasma hyopneumoniae in a pig herd suffering from respiratory disease

Abstract Background A randomised field trial was conducted on an Austrian farrow-to-finish farm for one year to compare the efficacy of two commercial Mycoplasma hyopneumoniae vaccines. 585 piglets either received the one-shot formulation in group 1 (Hyogen®, 23.9 days of age) or a two-shot vaccine (Stellamune® Mycoplasma, 4.3 and 24.0 days of age) in group 2. Assessment of vaccine efficacy was evaluated by regression analyses through cough monitoring from nursery to slaughter, average daily weight gain from inclusion to slaughter, antibiotic treatment rate (ATR), mortality rate, and lung lesion scoring at slaughter. Results In general, coughing was more frequent during late nursery and finishing. No significant differences were found in the coughing index (0.02 vs 0.03) and mean average daily weight gain (560 vs 550 g) between the two groups. ATR was higher in group 2 (3.8 vs 9.6%). At the slaughterhouse check, significant differences in the prevalence of bronchopneumonia (62.9 vs 71.2%) could be found. Extension of lung lesions was also significantly lower in group 1 in terms of enzootic pneumonia (EP) values (p = 0.000, z = − 4.269). There were no significant differences in the rate of scarred lungs (20.0 vs 24.0%) or those affected by dorsocaudal pleurisy (36.8 vs 34.3%). Conclusions This trial demonstrated that Hyogen® was superior to Stellamune® Mycoplasma in reducing (I) the prevalence of bronchopneumonic lungs and those affected by cranioventral pleurisy, (II) the extension and severity of EP-like lung lesions, and (III) the rate of antibiotically treated animals against respiratory disease

Evaluation of the Efficacy of a Vaccination Program against Actinobacillus pleuropneumoniae Based on Lung-Scoring at Slaughter

Porcine pleuropneumonia is of serious concern regarding lung health in pig production. Besides optimizing hygiene and pig management, specific vaccination against the causative agent, Actinobacillus pleuropneumoniae, is an important tool in the fight against this disease. As porcine pleuropneumonia may present with different clinical courses of disease, it is not always easy to objectively assess herd lung health state or to monitor improvements following specific therapeutic or prophylactic measures. Here, the effects of specific vaccination on lung health in a chronically diseased farrow-to-finish farm in Lower Austria experiencing an acute episode were monitored by means of an app-based electronic tool, enabling the scorers to document lung pathologies real-time at slaughter. At the time, when vaccination measures took effect, percentages of lungs affected by dorsocaudal pleurisy had decreased from 43 to 5 and the APP-index from 1.2 to 0.1, respectively. But not only pleurisies were diminished, also incidences and severities of bronchopneumonic alterations had dramatically decreased and exhibited interesting trends when set in connection to clinical signs. Overall, vaccination measures against Actinobacillus pleuropneumoniae proved to be very effective in restoring herd lung health

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system&rsquo;s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures