Kisspeptin Stimulates the Pulsatile Secretion of Luteinizing Hormone (LH) during Postpartum Anestrus in Ewes Undergoing Continuous and Restricted Suckling

This study tested whether the intravenous application of kisspeptin can stimulate the pulsatile secretion of LH in suckling ewes during postpartum anestrus. Ten days after lambing, Pelibuey ewes were allocated among two groups: (1) continuous suckling (n = 8), where the lambs remained with their mothers; and (2) restricted suckling (n = 8), where the mothers suckled their lambs twice daily for 30 min. On Day 19 postpartum, the ewes were individually penned with ad libitum access to water and feed and given an indwelling catheter in each jugular vein. On Day 20, 4 mL of blood was sampled every 15 min from 08:00 to 20:00 h to determine LH pulse frequency. At 14:00 h, four ewes in each group received 120 μg of kisspeptin diluted in 3 mL of saline as a continuous infusion for 6 h; the remaining four ewes in each group received only saline. The interaction between kisspeptin and suckling type did not affect LH pulse frequency (p > 0.05). Before kisspeptin administration, pulse frequency was similar in all groups (1.50 ± 0.40 pulses per 6 h; p > 0.05). With the application of kisspeptin, pulse frequency increased to 3.50 ± 0.43 pulses per 6 h (p ≤ 0.014), so the concentration of LH (1.11 ± 0.14 ng mL−1) was greater in kisspeptin-treated ewes than in saline-treated ewes (0.724 ± 0.07 ng mL−1; p ≤ 0.040). The frequency of LH pulses was greater with restricted suckling than with continuous suckling (2.44 ± 0.29 versus 1.69 ± 0.29 pulses per 6 h; p ≤ 0.040). We conclude that intravenous application of kisspeptin increases the pulsatile secretion of LH in suckling ewes and that suckling might reduce kisspeptin neuronal activity, perhaps explaining the suppression of ovulation. Moreover, the effects of kisspeptin and suckling on pulsatile LH secretion appear to be independent, perhaps operating through different neural pathways.

Safety Assessment of Intravenous Application of the Homeopathic Medicine Viscum Album D3 in Dogs

Background: Viscum album (VA) extracts have a wide variety of biologically active compounds that can be used in the treatment of various diseases, with cancer being the main one. However, few data on the effects of homeopathic VA are found in the literature, even though commercially VA formulations are available, with extremely low doses of its active compounds. Previous studies used the anthroposophical form of Viscum and provided information on the mechanisms of action of this drug in tumor cells or in cells of the immune system. Materials and methods: This study aimed to evaluate the safety of intravenous and subcutaneous application of D3 homeopathic Viscum album (VAD3) in dogs. Healthy dogs (n=7) underwent blood collection for blood cells count and biochemistry analysis and clinical examinations 7 days prior and at days 0, 3, 5, 7, 10, 12, and 14 after the beginning of treatment. The dogs received intravenous application of VAD3 at days 0, 5, 10, and 14, and subcutaneous at days 3, 7, and 12. Results: There was a transient increase in the number of monocytes (P=0.0022) at day 5, while there were no significant (P>0.05) changes in any of the other blood endpoints over time. Nevertheless, all blood parameters remained within the reference values for the species. All animals completed the study in good health conditions. According to the Quality-of-Life Assessment Questionnaire, all animals showed improvement in mood and appetite after receiving VAD3. Conclusion: The homeopathic medicine VAD3 is safe for intravenous and subcutaneous applications in dogs, besides possibly bringing benefits to the entire organism.

Dental Plaque Concentrations of Methadone, Morphine and Their Metabolites in Opioid Replacement Therapy and in Post-Mortem Cases

Non-mineralized dental biofilm (plaque) has potential as novel alternative matrix in forensic toxicology to prove drug use. The incorporation of illicit and medicinal drugs in dental plaque could take place through direct contact after oral or nasal intake, which can lead to high drug levels in the oral cavity, or indirectly via the secretion of drug-containing saliva, e.g. after intravenous application. Therefore, plaque samples from patients in opioid replacement therapy (ORT) and post-mortem plaque samples were analyzed and the drug concentrations were compared. The study comprised 26 plaque samples from ORT patients with different daily doses which were analyzed for methadone, morphine and their respective metabolites. Plaque samples were taken directly before the oral administration of the regular daily dose. Seventeen post-mortem plaque samples were analyzed, either from cases of lethal drug intoxications or after pain therapy with morphine. Plaque analysis was performed using LC-MS/MS after liquid extraction with acetonitrile. Plaque concentrations in ORT for methadone and its metabolite EDDP ranged from 42 to approx. 49,000 pg/mg (median 1,300 pg/mg) and from below 10 to 610 pg/mg (median 31 pg/mg), respectively. Morphine plaque concentrations in ORT ranged from 120 to 480 pg/mg (median 400 pg/mg). In lethal intoxication cases plaque concentrations were generally at least one order of magnitude higher than in the study groups with therapeutic substance use. This data will help to interpret drug findings in plaque. Additionally, the EDDP/methadone concentration ratio in plaque was lower after oral intake with contamination of the oral cavity (e.g. syrup) compared to cases with suspected intravenous application of methadone and could therefore indicate the drug administration route.

Comparison of Intra-Articular versus Intravenous Application of Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Study

Background: Total Knee Arthroplasty (TKA) is widely used in clinical applications. Considerable postoperative blood loss, however, is an unavoidable occurrence due to the extensive soft-tissue release, and the large area of cancellous bone osteotomy associated with the procedure. Besides, knee flexion and extension activities those begin the day after the operation adds to the problem. Aim of the Work: To compare between the intra-articular and the intravenous application of Tranexamic Acid (TXA) in total knee arthroplasty. Patients and Methods: It is a prospective Double-blinded Randomized controlled trial. This prospective study was conducted at El-Hussein University Hospital & El Agouza Hospital on 30 patients who undergo total knee arthroplasty and fulfill all inclusion and exclusion criteria. Results: The results were the average total blood loss in the drain after 48hrs. In the 1st group was 365±74.722 while average blood loss in the 2nd group was 575±88.976. This indicates a significant decrease in blood loss in the 1st group (intraarticular TXA group) than the 2nd group (intravenous TXA group) the P value <0.001 which is highly significant. It was found that The decrease in Hb level is less in the 1st group than in the 2nd group which indicates less postoperative anemia in the blood count, the P-value <0.05 considered significant.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB): An Update on the Pediatric CEUS Registry on Behalf of the “EFSUMB Pediatric CEUS Registry Working Group”

The European Federation of Ultrasound in Medicine and Biology (EFSUMB) created the “EFSUMB Pediatric Registry” (EFSUMB EPR) with the purpose of collecting data regarding the intravenous application of pediatric contrast-enhanced ultrasound (CEUS). The primary aim was to document the current clinical practice and usefulness of the technique and secondarily to assess CEUS safety in children. We issue the preliminary results of this database and examine the overall practice of CEUS in children in Europe.

Quality by Design Approach for Development and Optimization of Rifampicin Loaded Bovine Serum Albumin Nanoparticles and Characterization

Background: Rifampicin is one of the first line drugs used for tuberculosis therapy. The therapy lasts for a long time. Thus, there is a need to develop sustained release formulation of rifampicin for intravenous application. Aim: This study is focused on preparing rifampicin loaded bovine serum albumin nanoparticles (RIF BSA NPs) suitable for intravenous application using systematic quality by design (QbD) approach. Objectives: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin loaded bovine serum albumin nanoparticles (RIF BSA NPs) and making it suitable for intravenous application using QbD approach. Methods: Quality target product profile was defined along with critical quality attributes (CQAs) for the formulation. 32 factorial design was used for achieving the predetermined values of CQAs, i.e., mean particle size <200 nm and percent entrapment efficiency>50%. Incubation time of drug with colloidal albumin solution and ratio of rifampicin: albumin, were selected as independent variables. Check point analysis was performed to confirm the suitability of regression model for optimization. Results: : The optimized RIF BSA NPs were characterized by FTIR, DSC, 1H NMR techniques. The NPs observed by transmission electron microscopy were spherical in shape. The rifampicin release could be sustained for 72 hours from BSA NPs matrix. RIF BSA NPs dispersion was stable at 5 ± 3°C for 72 hours. Non-toxicity of nanoparticles to RAW 264.7 cell line was proved by MTT assay. Conclusion: Development of RIF BSA NPs with desired quality attributes was possible by implementing QbD approach. The optimized formulation suitable for intravenous application can potentially improve the therapeutic benefits of rifampicin.