Plasma and Red Blood Cells Concentration Profiles of Ktamine after Single Intravenous Administration in an Anaesthetic Protocol in Horses

The aim of this study was to describe the concentration profile of ketamine in plasma and red blood cells following an intravenous (IV) bolus in the horse. Ten healthy standardbred horses (two males and height females) 7.7 ± 4.6 (mean value ± SD) years old and weighting 380 ± 21 kg (mean value ± SD) were recruited. The horses were premedicated with acepromazine (0.04 mg·kg-1·IV). Fifteen minutes later they received romifidine (0.08 mg·kg-1·IV), and 5 minutes after they were administered midazolam (0.06 mg·kg-1·IV). Immediately, anaesthesia was induced by ketamine (2.2 mg·kg-1·IV). Venous blood samples were collected at scheduled time points. Plasma and red blood cells (RBCs) concentration of ketamine was assayed using a high performance liquid chromatographic method (HPLC/UV-DAD). The high mean recovery rates, the high sensitivity, the good linearity, suggest a clinical applicability of the analytical method. A bicompartmental model resulted as the most appropriate to describe the ketamine concentration—time profile for both plasma and RBCs. The fitted regression line between ketamine plasma concentrations and RBC concentrations supports the good correlation between ketamine concentrations in plasma and in RBCs. The kinetic parameters of ketamine calculated for RBC are equal or very similar to the plasma ones. The study confirms the kinetic behaviour of ketamine used in the horse as anaesthetic inducers in routine surgery. Finally, the bicompartmental model well describes the ketamine profile also in RBCs, that it is very close to the plasma profile, underlining the great importance of RBCs as blood subcompartment

Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial

Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle

Pharmacokinetic profile and partitioning in red blood cells of romifidine after single intravenous administration in the horse

The aims of this study were to assess the plasma concentrations of romifidine in horses after intravenous injection, to evaluate the red blood cell (RBC) partitioning of the anaesthetic drug, and to improve knowledge regarding its sedative effect in horses describing the pharmacokinetic model. Eight adult Standardbred horses received a single bolus of romifidine at a dosage of 100\ua0\u3bcg/kg. Blood samples (5\ua0mL) were collected immediately before romifidine administration (t0), and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180\ua0min after injection. A sedation score was recorded at the same time. The romifidine concentrations in plasma and red blood cells were determined by high performance liquid chromatography (HPLC). The plasma and red blood cell concentrations were correlated with the sedation at each time point. Romifidine produced a satisfactory level of sedation in all animals. The sedation was detectable in all horses for up to 105\ua0min. All the animals returned to normal without any behavioural changes at 180\ua0min. The romifidine concentrations in the red blood cells were significantly higher (P\ua0<\ua00.01) at all time points than those in the plasma. The T1/2\u3b2 was 148.67\ua0\ub1\ua061.59\ua0min and body clearance was 22.55\ua0\ub1\ua06.67\ua0mL/kg per min. The results showed that after a single bolus administration of romifidine, a partitioning in the RBCs was detected

Translocation of signalling proteins to the plasma membrane revealed by a new bioluminescent procedure

<p>Abstract</p> <p>Background</p> <p>Activation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors.</p> <p>High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive.</p> <p>Results</p> <p>Here we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca²⁺)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca²⁺ concentration [Ca²⁺] difference between bulk cytosolic and the sub-plasma membrane rim.</p> <p>Conclusion</p> <p>This approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane.</p> <p>Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation.</p> <p>Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process.</p

The archaeal elongation factor EF-2 induces the release of aIF6 from 50S ribosomal subunit

The translation factor IF6 is a protein of about 25 kDa shared by the Archaea and the Eukarya but absent in Bacteria. It acts as a ribosome anti-association factor that binds to the large subunit preventing the joining to the small subunit. It must be released from the large ribosomal subunit to permit its entry to the translation cycle. In Eukarya, this process occurs by the coordinated action of the GTPase Efl1 and the docking protein SBDS. Archaea do not possess a homolog of the former factor while they have a homolog of SBDS. In the past, we have determined the function and ribosomal localization of the archaeal (Sulfolobus solfataricus) IF6 homolog (aIF6) highlighting its similarity to the eukaryotic counterpart. Here, we analyzed the mechanism of aIF6 release from the large ribosomal subunit. We found that, similarly to the Eukarya, the detachment of aIF6 from the 50S subunit requires a GTPase activity which involves the archaeal elongation factor 2 (aEF-2). However, the release of aIF6 from the 50S subunits does not require the archaeal homolog of SBDS, being on the contrary inhibited by its presence. Molecular modeling, using published structural data of closely related homologous proteins, elucidated the mechanistic interplay between the aIF6, aSBDS, and aEF2 on the ribosome surface. The results suggest that a conformational rearrangement of aEF2, upon GTP hydrolysis, promotes aIF6 ejection. On the other hand, aSBDS and aEF2 share the same binding site, whose occupation by SBDS prevents aEF2 binding, thereby inhibiting aIF6 release

Length of efficacy and effect of implant location in adult tom cats treated with a 9.4 mg deslorelin subcutaneous implant

Objectives The objective of this study was to assess duration of efficacy, side effects and return to fertility following use of the 9.4 mg deslorelin implant (Suprelorin 12; Virbac) in cats, and test whether efficacy and duration of action are influenced by implantation site (interscapular vs periumbilical). Methods Sixteen healthy adult tom cats were checked with (1) reproductive examination, (2) gonadotropin-releasing hormone stimulation test and (3) semen collection until achievement of sterility, then with (1) and (2) only at 2, 4, 6 and 12 months, and every 6 months thereafter until treatment effect disappeared. Results Serum testosterone reached basal levels by 7 days post-treatment. Semen quality improved initially then started to worsen by 1 month post-treatment and after 70 days post-treatment all cats were sterile. Early in the third month post-treatment there was a significant decrease in testicular volume and penile spikes. Testicular histology was normal upon neutering performed after resumption of fertility. No injection site lesions or treatment-related side effects were observed. There was no difference between periumbilical and interscapular placement for all criteria, but there was a trend for the decrease in testicular volume to last longer and for the regression of penile spikes to start sooner after interscapular administration. One of 16 cats did not respond to treatment. Six cats were lost at variable times during the study while fully responding to treatment. In the cats that completed the study, normal fertility was regained after 805 days, on average, but with a variable duration of effect from 750-850 days. Conclusions and relevance Treatment with a 9.4 mg deslorelin implant in male cats was effective for a period of 750-850 days, 1.5-2 times longer than the effect of the 4.7 mg deslorelin implant. Fertility (based on serum testosterone production and presence of penile spikes) was regained at the end of the study. Placing implants in the intrascapular vs periumbilical location did not affect duration of suppression of testosterone production. The interscapular location may be characterised by a better efficacy, although further studies are needed to clarify this issue

SWOT Analysis Approach for Advancement of Waste-to-energy Cluster in Latvia

AbstractIt is important to improve the communication and collaboration of waste-to-energy stakeholders in Latvia to ensure sustainable economic and environmental development and promote innovation and local technology development. Therefore, implementation of a waste-to-energy cluster in Latvia has been proposed. The aim of this paper is to provide a comparative analysis of the organizational structure and SWOT analysis of five existing and one potential waste-to-energy cluster and develop suggestions for improved organization of the developing Latvian cluster. The analytical part includes SWOT analysis of the proposed Latvian waste-to-energy cluster and a comparison of its results with five SWOT analyses for existing European waste-to-energy clusters involved in the project COOLSWEEP

Acupuncture decreases pain and MIF salivary levels in men and women

Acupuncture is used worldwide to treat many diseases, including painful conditions. Acupuncture-induced effects on pain were studied in men and women to understand the various factors involved in this positive procedure able to cure patients without side effects. Vital parameters (heart rate, blood pressure, temperature) were measured and questionnaires about quality of life (SF-36), mood state (POMS) and pain condition (QUID) were administered to men and women requesting acupuncture treatment for pain. Macrophage inhibitory factor (MIF) was determined in the saliva. All parameters were determined before the first and tenth acupuncture sessions. Pain scores (questionnaire and scales) significantly decreased from the first to the last acupuncture session in both sexes. Vital parameters were not affected, while the other questionnaires indicated a general improvement in the quality of life. MIF salivary levels were higher in males than in females and were significantly decreased by acupuncture in both sexes

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review

BACKGROUND Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND " and "OR " Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy

Management of major bleeding in patients treated with direct oral anticoagulants: From experience to standardized protocols

Evaluation of clinical-laboratory-therapeutic management and related clinical outcomes (thrombotic-hemorrhagic complications) of patients undergoing treatment with direct oral anticoagulants (DOACs) during major bleeding. This is a two-year observational retrospective study. 27 cases of major bleeding in patients undergoing a therapy with DOACs presented to the Emergency Department of Arcispedale Santa Maria Nuova (Reggio Emilia Hospital). 16 cases (59%) underwent reversal of anticoagulation treatment: 19% using specific reversal therapy (idarucizumab) and 81% using non-specific agents [4-factor prothrombin complex concentrate (4F-PCC)]. Routine laboratory data were available for all the cases, but only for some patients it was possible to obtain the plasma dosage of the oral anticoagulant. Laboratory data confirm rapid correction of activated partial thromboplastin time within one hour from the reversal of anticoagulation with idarucizumab. The absence of correlation between standard blood tests and plasma drug dosage in patients treated with factor Xa Inhibitors was confirmed too. The management of major bleeding during treatment with DOACs using reversal therapy (idarucizumab) and non-specific reversal agent (4F-PCC) showed minimal thrombotic (0.3%) and hemorrhagic (0.3%) complications at 90 days; no events occurred after 6 months