Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep

Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6\u2009mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6\u2009h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep

Genetical stability and osteogenic ability of mesenchimal stem cells on demineralized bone matrices

Journal of Osseointegration Volume 7, Issue 1, 1 March 2015, Pages 2-7 Open Access Genetical stability and osteogenic ability of mesenchimal stem cells on demineralized bone matrices (Article) Pozzuoli, A.a, Gardin, C.b, Aldegheri, R.a, Bressan, E.c, Isola, M.d, Calvo-Guirado, J.L.e, Biz, C.a, Arrigoni, P.a, Feroni, L.b, Zavan, B.b a Department of Surgical,Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy b Department of Biomedical Sciences, University of Padua, Padua, Italy c Department of Neurosciences, University of Padua, Padua, Italy d Department of Animal Medicine, Production and Health (MAPS), Italy e Department of General Dentistry, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain Hide additional affiliations View references (44) Abstract Aim: Tissue engineering is a rapidly expanding field with regard to the use of biomaterials and stem cells in the orthopedic surgery. Many experimental studies have been done to understand the best characteristics of cells, materials and laboratory methods for safe clinical applications. The aim of this study was to compare the ability of 2 different human demineralized bone matrices (DBMs), the one enriched and the other not enriched with hyaluronic acid, to stimulate in vitro the proliferation and the osteogenic differentiation of human adipose-derived stem cells (ADSCs) seeded onto an osteoconductive scaffold. Materials and Methods: ADSCs were isolated, by enzymatic digestion, from abdominal adipose tissue of 5 patients undergoing cosmetic lipoaspiration surgery. ADSCs were then seeded onto a 3D scaffold in the presence of the two different osteoinductive matrices of human demineralized bone and evaluated for proliferation and osteogenic differentiation. The safety of the methods was verified using array-Comparative Genomic Hybridization (array-CGH). Results: ADSCs were able to differentiate in osteogenic sense. Both DBMs showed the ability to induce osteogenic differentiation of the cells. Conclusion: array-CGH showed no changes at genome level, thus confirming the safety of materials and method

Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures

The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications

Quality of life 1 year after hospital discharge in unvaccinated pregnant women with COVID-19 respiratory symptoms: a prospective observational study (ODISSEA-PINK study)

IntroductionLittle is known about Quality of Life within the first court of unvaccinated COVID-19 pregnant women exposed to the pandemic stressor. Primary aim of this study was to evaluate 1 year after hospital discharge HRQoL in a cohort of COVID-19 unvaccinated pregnant patients with COVID-19.Methodsin this prospective observational study, all COVID-19 positive pregnant women at any gestational age, admitted to the Obstetric Department at the University Hospital of Udine, Italy, from 1 March 2020 to 1 March 2021, requiring or not oxygen supplementation due to SARS-CoV2 pneumonia were evaluated. Patients with a history of neurological or psychiatric disease, those with a previous abortion, and those who refused to provide written informed consent were excluded from the study. We investigated pregnant positive COVID-19 women Health-related quality of life (HRQoL) with the Short-Form Health Survey-36 (SF-36) and Post-traumatic Stress-Disorder (PTSD) with the Impact of Event Scale-Revised (IES-R).Results62 pregnant women respected the inclusion criteria of the study, and data from 33 patients were analyzed. The mean age was 32 ± 6 years, with a median gestational age of 38 weeks [IQR 34–40]. 15.2% of patients required oxygen therapy through noninvasive respiratory support (with high flow nasal cannula) for a median of 9 days [IQR 6–12]. The median Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were 50.2 [IQR 46.7–53.7] and 56.0 [IQR 46.8–60.6] respectively. Ten patients out of 33 (30%) tested positive for PTSD. Maternal age, gestational age, and history of cardiac-pulmonary-kidney disease significantly affected HRQoL at multivariable analysis.DiscussionIn COVID-19 pregnant unvaccinated women some physical impairments reducing HRQoL are still present 1 year after hospital discharge. Previous medical history such as history of cardiac-pulmonary-kidney disease significantly affected HRQoL. Long and repeated follow-up should be pursued in this category of patients.Clinical trial registration:ClinicalTrials.gov, Identifier NCT04860687

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Internal fixation for the treatment of multiple physeal tibial fractures in a growing dog

This case report describes pinning fixation for the treatment of three tibial physeal fractures in a 3-month old mixed-breed dog. The radiographic study revealed a severe proximal dislocation of the tibial diaphysis along with multiple, closed fractures of the proximal and distal tibial physes, distal femoral physis and the fibula. Open reduction and internal fixation (ORIF) were performed using crossed Kirschner wires for proximal and distal tibial physeal fixation and a tension band to manage the tibial tuberosity avulsion fracture. Postoperative radiographs showed proper fracture reduction, tibial alignment and correct implant positioning. Clinical and radiographic checks documented progressive limb weight-bearing, gradual resolution of distal limb oedema and fracture healing. The described open surgical treatment had a satisfactory clinical outcome with restoration of tibial anatomy, preservation of joint function and an early return to normal motor activity at 45 days of follow-up