Postmenopausal bone loss : prevention and replacement

Osteoporosis is a skeletal disorder predominantly affecting postmenopausal women. Combination therapy of Carbocalcitonin (Elcatonin) and oral conjugated oestrogens (Premarin) not only prevents postmenopausal bone loss but leads to an increase in bone mass in normal early postmenopausal women. The aims of the study was to investigate the effect of combination therapy. A combination of Elcatonin (Carbo calcitonin) and Premarin was compared to Premarin alone, and to Elcatonin (Carbocalcitonin) alone and all groups were then compared to a control group.peer-reviewe

Oxidative potential of atmospheric aerosols

Atmospheric particulate matter (PM) is one of the leading health risks worldwide [1,2]. Several epidemiological studies have provided evidence of the association between exposure to PM and the onset of cardiovascular and respiratory diseases [3], as well as cardiopulmonary diseases and other adverse health effects [4]. The exact mechanisms leading to PM toxicity are not fully known, however, several studies suggest that the generation of reactive oxygen species (ROS) could be a major mechanism by which PM leads to both chronic and acute adverse health effects [5,6]. For this reason, in recent years, the oxidative potential (OP) of PM, defined as its ability to generate oxidative stress in biological systems, has been proposed as a relevant metric for addressing PM exposure [7,8]. However, the link between OP and adverse health effects is still uncertain [9–11], and contrasting results have been obtained when PM oxidative potential has been compared with the results of in-vivo and in-vitro toxicological tests or the outcomes of epidemiological studies [12]. The OP can be evaluated through several in vitro assays, but protocols employing chemical (acellular) assays have become common as well. Acellular assays can be useful for investigating the PM properties which are responsible for oxidative stress: ROS compounds can either be carried by components of the aerosol itself (particle-bound ROS) or induced by the catalytic activity exerted by aerosol constituents (PM-induced ROS). The diverse OP assays developed so far have certainly improved our knowledge of the mechanisms underlying PM oxidative stress. At the same time, they pose the issue of comparability between the different assays and protocols, as well as problems surrounding the actual correlation between acellular OP and in vitro (or in vivo) toxicity. Measurements of PM oxidative potential are influenced by the chemical composition of the aerosol, by its size distribution, and by the weight of different natural and anthropogenic sources of PM leading to temporal and spatial variabilities that need investigation in current research. Moreover, recent studies show that photochemical aging increases the oxidative potential of atmospheric aerosols. However, several aspects regarding the specific chemical species, aerosol sources, and atmospheric processes that affect OP are not well established, and further research is needed [13–15]. Another topic that needs extensive research is the characterization of the OP of indoor aerosols. This special issue includes five research papers and two review papers discussing recent advances in the studies of the oxidative potential of atmospheric particulate matter

DNA Nucleobase Synthesis at Titan Atmosphere Analog by Soft X-rays

Titan, the largest satellite of Saturn, has an atmosphere chiefly made up of N2 and CH4 and includes traces of many simple organic compounds. This atmosphere also partly consists of haze and aerosol particles which during the last 4.5 gigayears have been processed by electric discharges, ions, and ionizing photons, being slowly deposited over the Titan surface. In this work, we investigate the possible effects produced by soft X-rays (and secondary electrons) on Titan aerosol analogs in an attempt to simulate some prebiotic photochemistry. The experiments have been performed inside a high vacuum chamber coupled to the soft X-ray spectroscopy beamline at the Brazilian Synchrotron Light Source, Campinas, Brazil. In-situ sample analyses were performed by a Fourier transform infrared spectrometer. The infrared spectra have presented several organic molecules, including nitriles and aromatic CN compounds. After the irradiation, the brownish-orange organic residue (tholin) was analyzed ex-situ by gas chromatographic (GC/MS) and nuclear magnetic resonance (1H NMR) techniques, revealing the presence of adenine (C5H5N5), one of the constituents of the DNA molecule. This confirms previous results which showed that the organic chemistry on the Titan surface can be very complex and extremely rich in prebiotic compounds. Molecules like these on the early Earth have found a place to allow life (as we know) to flourish.Comment: To appear in Journal of Physical Chemistry A.; Number of pages: 6; Number of Figures: 5; Number of Tables: 1; Number of references:49; Full paper at http://pubs.acs.org/doi/abs/10.1021/jp902824

Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV

Preliminary classification criteria for the cryoglobulinaemic vasculitis

To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV)

Invasive meningococcal disease in three siblings with hereditary deficiency of the 8th component of complement: Evidence for the importance of an early diagnosis

Deficiency of the eighth component of complement (C8) is a very rare primary immunodeficiency, associated with invasive, recurrent infections mainly caused by Neisseria species. We report functional and immunochemical C8 deficiency diagnosed in three Albanian siblings who presented with severe meningococcal infections at the age of 15 years, 4 years and 17 months, respectively. The youngest suffered serious complications (necrosis of fingers and toes requiring amputation). METHODS: Functional activity of the classical, alternative and mannose-binding lectin complement pathways was measured in serum from the 3 siblings and their parents (37-year-old woman and 42-year-old man). Forty healthy subjects (20 males and 20 females aged 4-38 years) served as normal controls. Serum complement factors were measured by haemolytic assays and immunoblotting. Sequence DNA analysis of the C8B gene was performed. RESULTS: Analyses of the three complement pathways revealed no haemolytic activity and also absence of C8beta in serum samples from all three siblings. The genetic analysis showed that the three siblings were homozygous for the p.Arg428* mutation in the C8B gene on chromosome 1p32 (MIM 120960). The parents were heterozygous for the mutation and presented normal complement activities. A 2-year follow-up revealed no further infective episodes in the siblings after antibiotic prophylaxis and meningococcal vaccination. CONCLUSIONS: Complement deficiencies are rare and their occurrence is often underestimated. In presence of invasive meningococcal infection, we highlight the importance of complement screening in patients and their relatives in order to discover any genetic defects which would render necessary prophylaxis to prevent recurrent infections and severe complications

The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999–2019)

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data collected from the IPINet registry after 20\ua0years of activity. A total of 3352 pediatric and adult patients affected with PIDs are registered in the database. In Italy, a regional distribution trend of PID diagnosis was observed. Based on the updated IUIS classification of 2019, PID distribution in Italy showed that predominantly antibody deficiencies account for the majority of cases (63%), followed by combined immunodeficiencies with associated or syndromic features (22.5%). The overall age at diagnosis was younger for male patients. The minimal prevalence of PIDs in Italy resulted in 5.1 per 100.000 habitants. Mortality was similar to other European registries (4.2%). Immunoglobulin replacement treatment was prescribed to less than one third of the patient cohort. Collectively, this is the first comprehensive description of the PID epidemiology in Italy

Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required