The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment

In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75?mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was ?2.80?±?0.63 before therapy and ?2.64?±?0.45 6 months later (p?<?0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p?<?0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase. The analysis of the activity of biochemical markers may obtain early information on the therapeutic response, before definitive assessment by bone density measurements.     

Pharmacology of vagal afferent influences on disordered breathing during sleep

Sleep-related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of approximately 2% of women and approximately 4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep-related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved.     

Characterization and functional analysis of goldfish (Carassius auratus L.) tumor necrosis factor-alpha

We identified and characterized two isoforms of tumor necrosis factor-alpha (TNFalpha) from the goldfish, TNFalpha-1 and TNFalpha-2. At the protein level, goldfish TNFalpha-1 and TNFalpha-2 were most homologous to carp TNFalpha-1 and TNFalpha-2, respectively. Phylogenetically, the two goldfish isoforms grouped most closely with the carp TNFalpha isoforms and TNF species of other cyprinids. Real-time PCR analysis revealed constitutive expression of goldfish TNFalpha-1 and TNFalpha-2 in all tissues with TNFalpha-2 mRNA levels higher than TNFalpha-1 in all tissues examined. A modest up-regulation in expressions of goldfish TNFalpha-1 and TNFalpha-2 in kidney-derived monocytes and significant increase in expression of both isoforms in mature macrophages were observed in response to activation with macrophage-activating factors. TNFalpha-2 was subsequently expressed using a prokaryotic expression system and the recombinant molecule (rTNFalpha-2) was functionally characterized. The rTNFalpha-2 induced a dose-dependent chemotactic response and enhanced phagocytosis of primary goldfish macrophages. Furthermore, rTNFalpha-2 primed the respiratory burst in monocytes and induced nitric oxide production of primary goldfish macrophages. Our results indicate that goldfish TNFalpha is a central regulatory and effector cytokine of inflammatory and antimicrobial responses of the goldfish.     

Safety and efficacy of dual antiplatelet therapy after percutaneous coronary interventions in patients with end-stage liver disease

The prevalence of coronary artery disease (CAD) increases in patients with end-stage liver disease, with part of them receiving the percutaneous coronary intervention (PCI) as a treatment option. Dual antiplatelet therapy (DAPT), a standard of care after PCI, could result in catastrophic consequences in this population. Before PCI and the start of DAPT, it is recommended to assess patient bleeding risk. Based on novel findings, liver cirrhosis does not necessarily lead to a significant increase in bleeding complications. Furthermore, conventional methods, such as the international normalized ratio, might not be appropriate in assessing individual bleeding risk. The highest bleeding risk among cirrhotic patients has a subgroup with severe thrombocytopenia (< 50 × 10⁹/L) and elevated portal pressure. Therefore, every effort should be made to maintain thrombocyte count above > 50 × 10⁹/L and prevent variceal bleeding. There is no solid evidence for DAPT in patients with cirrhosis. However, randomized trials investigating short (one month) DAPT duration after PCI with new drug-eluting stents (DES) in a high bleeding risk patient population can be implemented in patients with cirrhosis. Based on retrospective studies (with older stents and protocols), PCI and DAPT appear to be safe but with a higher risk of bleeding complications with longer DAPT usage. Finally, novel methods in assessing CAD severity should be performed to avoid unnecessary PCI and potential risks associated with DAPT. When indicated, PCI should be performed over radial artery using contemporary DES. Complementary medical therapy, such as proton pump inhibitors and beta-blockers, should be prescribed for lower bleeding risk patients. Novel approaches, such as thromboelastography and “preventive” upper endoscopies in PCI circumstances, warn clinical confirmation.     

Surgical reconstruction of the dissected innominate artery using extra-anatomic aorto-axillar bypass

The innominate artery is the most commonly affected supra-aortic vessel in the acute ascending aorta dissection. The brachiocephalic vessels, separated from the true lumen, need reimplantation. The fragile vessel tissue might be challenging to reconstruct. Cerebral blood flow could be restored using an extra-anatomic bypass.