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SrFe12O19 (SFO) films grown on Si (100) substrates by radio-frequency magnetron sputtering have been characterized in terms of composition, structural and magnetic properties by a combination of microscopy, diffraction and spectroscopy techniques. Mössbauer spectroscopy was used to determine the orientation of the films magnetization, which was found to be controlled by both the sputtering power and the thickness of the films. Additionally, the coupling between the SFO films and a deposited cobalt overlayer was studied by means of synchrotron-based spectromicroscopy techniques. A structural coupling at the SFO/Co interface is suggested to account for the expetimental observations. Micromagnetic simulations were performed in order to reproduce the experimental behaviour of the system. [ABSTRACT FROM AUTHOR]

Background: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an angiotensin-converting enzyme inhibitor indicated in the management of essential and renovascular hypertension, and in the treatment of congestive heart failure and in asymptomatic patients with left ventricular dysfunction and an ejection fraction of >/=35%. Enalapril has little pharmacologic activity until hydrolyzed in vivo to enalaprilat.Objective: The aim of the present study was to compare the bioavailability and tolerability of 2 commercial brands (test and reference formulations) of enalapril tablets (20 mg), described as the rate and extent of absorption of the active moiety, to assess their bioequivalence.Methods: This single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit, Hospital Clínico San Carlos (Madrid, Spain). Subjects were randomized to receive (under fasting conditions) either the test or reference formulation of enalapril (20-mg tablet) at study period 1 and the opposite formulation at study period 2. Study periods were separated by a washout period of at least 7 days. During each study period, 15 plasma extractions were made to determine enalapril and enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK) properties (maximal plasma drug concentration [C(max)], time to C[max] [T[max]], area under the plasma concentration-time curve [AUC] to the last measurable concentration [AUCt], AUC from time 0 to infinity [AUC(0-infinity)], mean residence time, and elimination half-life [t(l/2)]) of both. Physical examination, subject interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were used to assess tolerability.Results: Twenty-four subjects were included in the study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]). Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK and statistical analyses included results from 23 subjects. No statistically significant sequence or period effect was found. T[max] was not statistically different between the 2 formulations, and the 90% CI calculated for T[max] for the difference of the medians was within the predefined range. The 90% CIs of the logarithmically transformed concentration-derived parameters (C([max]) AUC[t], and AUC[0-infinity]) also were within the predefined range; thus, the 2 formulations are considered bioequivalent. For both formulations, systolic and diastolic BPs showed significant reductions compared with baseline values (P < 0.05). Seven adverse effects were recorded, all of them transient and none of severe intensity.Conclusions: In this study of 2 commercial brands (test and reference formulations) of enalapril in healthy subjects, designed and conducted under Good Clinical Practice guidelines, a similar rate and extent of absorption for both formulations were found to be bioequivalent. Both formulations produced a significant decrease in BP values and were generally well tolerated. [ABSTRACT FROM AUTHOR]

Regenerative Peripheral Nerve Interfaces (RPNIs) encompass neurotized muscle grafts employed for the purpose of amplifying peripheral nerve electrical signaling. The aim of this investigation was to undertake an analysis of the extant literature concerning animal models utilized in the context of RPNIs. A systematic review of the literature of RPNI techniques in animal models was performed in line with the PRISMA statement using the MEDLINE/PubMed and Embase databases from January 1970 to September 2023. Within the compilation of one hundred and four articles employing the RPNI technique, a subset of thirty-five were conducted using animal models across six distinct institutions. The majority (91%) of these studies were performed on murine models, while the remaining (9%) were conducted employing macaque models. The most frequently employed anatomical components in the construction of the RPNIs were the common peroneal nerve and the extensor digitorum longus (EDL) muscle. Through various histological techniques, robust neoangiogenesis and axonal regeneration were evidenced. Functionally, the RPNIs demonstrated the capability to discern, record, and amplify action potentials, a competence that exhibited commendable long-term stability. Different RPNI animal models have been replicated across different studies. Histological, neurophysiological, and functional analyses are summarized to be used in future studies.

Objective: To evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles., Study Design: Randomized, blinded, crossover, experimental study., Animals: Six healthy adult Beagles., Methods: Dogs were randomly given three treatments: dexmedetomidine (3 μg kg -1 ) and methadone (0.3 mg kg -1 ) combined with ketamine at 1 and 2 mg kg -1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran's Q tests; p < 0.050., Results: Increased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3-12 minutes) and duration of recumbency (29-51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively., Conclusions and Clinical Relevance: The addition of 1 or 2 mg kg -1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles., Study Design: Randomized, blinded, crossover, experimental study., Animals: A group of six adult Beagles., Methods: Dogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg -1 ) and methadone (0.3 mg kg -1 ) combined with two doses of alfaxalone (0.5 and 1 mg kg -1 ; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO 2 ) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran's Q tests. Significance was p < 0.05., Results: Sedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum-maximum), 43 (35-54) versus 30 (20-47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO 2 ., Conclusions and Clinical Relevance: Adding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The anesthetic management in patients with subaortic stenosis and mitral valve disease should involve intensive monitoring and the anesthesiologist's main concern is to ensure oxygen delivery and tissue perfusion. Since anesthetic procedures in such patients are rare, there is no previous report about the anesthetic management. A 5.5-year old, 32-kg Boxer, suffering a severe heart disease due to a final stage subaortic stenosis and mitral insufficiency, was anesthetized for an ovariohysterectomy to remove an ovarian tumor that was producing high-volume ascites. Methadone (0.3 mg kg -1 ) was administered intramuscularly (IM) for pre-anesthetic medication, etomidate (1.3 mg kg -1 ) and midazolam (0.2 mg kg -1 ) were used for the induction of anesthesia and after endotracheal intubation, anesthesia was maintained with sevoflurane vaporized in oxygen and air. Fentanyl (5-10 μg kg -1 h -1 ) and paracetamol (15 mg kg -1 ) were administered to improve analgesia. Previous persistent atrial fibrillation was refractory to medication (digoxin, diltiazem, and pimobendan) and continued during the anesthetic procedure. Dobutamine (1.5-5 μg kg -1 minute -1 ) helped to maintain mean arterial blood pressure above 60 mmHg. Epidural morphine (0.1 mg kg -1 ) and incisional bupivacaine (2 mg kg -1 ) were administered at the end of surgery to provide postoperative analgesia. Anesthesia was otherwise uneventful, and recovery was considered excellent., Competing Interests: The authors declare that there is no conflict of interest.

Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg -1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg -1 , females; 75 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ). Finally, alfaxalone (20 mg kg -1 , females; 60 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ) and fentanyl (0.1 mg kg -1 ). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.

Objectives: The new European Union directives affecting clinical trials of medicines introduced important changes for Spain, leading to the publication of a Royal Decree regulating the conduct of clinical trials that went into effect in January 2016. The decree sets out the principles for complying with the EU directives, regulates the work of institutional review boards (IRBs) or ethics committees that review research proposals, introduces means to facilitate clinical research, and clarifies the role of the Spanish register of clinical trials, among other topics. This paper discusses the main changes that have been introduced, especially those intended to facilitate research, such as the new concepts of low intervention trial and noncommercial clinical research. These concepts may be particularly useful for clinical trials designed by emergency medicine physicians. We also comment on changes affecting vulnerable populations and the documents that must be presented to both the researchers' IRB and the Spanish Agency for Medicines and Health Care Products.

Background: A quantitative and qualitative assessment of reports on suspected adverse drug reactions (ARD) in Spanish medical literature was carried out., Materials and Methods: The periods analysed were 1972-1974, 1986-1988 and 1992-1994, and the medical journals were Anales de Medicina Interna, Medicina Clínica and Revista Clínica Española. We selected all articles including specific information on suspect ADR., Results: The percentage of articles has increased considerably (1972-1974: 2.1%, 1986-1988: 5.7%, and 1992-1994: 8.2%). In spite of this growth, the qualitative data studied have not significantly improved., Conclusions: It is necessary to device some mechanism in order to improve ADR reporting.