Search

ObjectivesTo develop alginate nanoparticles functionalized with polysorbate 80 (P80) as miltefosine carriers for brain targeting in the oral treatment of cryptococcal meningitis.MethodsMiltefosine-loaded alginate nanoparticles functionalized or not with P80 were produced by an emulsification/external gelation method and the physicochemical characteristics were determined. The haemolytic activity and cytotoxic and antifungal effects of nanoparticles were assessed in an in vitro model of the blood-brain barrier (BBB). A murine model of disseminated cryptococcosis was used for testing the efficacy of oral treatment with the nanoparticles. In addition, serum biomarkers were measured for toxicity evaluation and the nanoparticle biodistribution was analysed.ResultsP80-functionalized nanoparticles had a mean size of ∼300 nm, a polydispersity index of ∼0.4 and zeta potential around -50 mV, and they promoted a sustained drug release. Both nanoparticles were effective in decreasing the infection process across the BBB model and reduced drug cytotoxicity and haemolysis. In in vivo cryptococcosis, the oral treatment with two doses of P80 nanoparticles reduced the fungal burden in the brain and lungs, while the non-functionalized nanoparticles reduced fungal amount only in the lungs, and the free miltefosine was not effective. In addition, the P80-functionalization improved the nanoparticle distribution in several organs, especially in the brain. Finally, treatment with nanoparticles did not cause any toxicity in animals.ConclusionsThese results support the potential use of P80-functionalized alginate nanoparticles as miltefosine carriers for non-toxic and effective alternative oral treatment, enabling BBB translocation and reduction of fungal infection in the brain.

Approach: Both 2D and 3D biomechanical analyses (BA) offer valuable insights into running technique. While BA3D is considered the gold standard, it requires substantial investments, whereas BA2D is cost-effective and increasingly employed in clinical settings. The primary aim of this study was to establish correlations between sagittal plane angles derived from BA2D and BA3D for the pelvis, hip, knee, and ankle during the initial contact phase of running. Methods: Twelve runners, consisting of six females (34.0 ± 5.0 years, 53.0 ± 9.5 kg, and 162.0 ± 6.0 cm) and six males (32.0 ± 3.0 years, 70.0 ± 6.2 kg, and 175.0 ± 8.0 cm), underwent initial contact kinematics assessment using BA3D (Vicon Nexus 1.8 and Polygon 4 plug-in gait model) and BA2D (Kinovea, Version 0.9.3). Correlations between measurements were determined through linear regression (R²), mean differences, Bland & Altman analysis (B&A), Pearson correlation coefficient (r) between BA2D and BA3D, and intraclass correlation coefficient (ICC). Results: The following results were obtained: Pelvis R² = 0.67, B&A = 7.32° ± 3.69°, r = 0.818 (sufficient, p < 0.001); Hip: R² = 0.48, B&A = 18.39° ± 5.56°, r = 0.690 (moderate, p = 0.123); Knee: R² = 0.13, B&A = 2.54° ± 5.38°, r = 0.364 (insufficient, p < 0.001); Ankle R² = 0.15, B&A = -4.89° ± 4.22°, r = 0.386 (insufficient, p < 0.001). ICC for pelvis = 0.470; hip = 0.286; knee = 0.322; ankle = 0.213 (all statistically considered poor). Conclusion: The setup used during data collection can be easily reproduced by other professionals in a clinical setting. A low difference between BA2D and BA3D methods was observed based on B&A analysis. A linear relationship with moderate variability was established according to the Pearson correlation coefficient and coefficient of determination. However, poor agreement between BA3D and BA2D was found, as indicated by ICC. Therefore, caution is warranted when interpreting BA2D results relative to BA3D. The present study does not recommend other researchers to compare their BA2D with BA3D results conducted by different software than those used in our methods, this type of data must be considered individually across studies. [ABSTRACT FROM AUTHOR]

The objective of the study is to evaluate the anesthetic effect produced by the tiletamine/zolazepam association in horses sedated with medetomidine undergoing orchiectomy under field conditions. Ten uncastrated male horses, American Society of Anesthesiologists category I, undergoing orchiectomy, were enrolled in the study. The horses received acepromazine (0.03 mg kg −1 intramuscularly) 30 minutes before sedation with medetomidine (8 μg kg −1 intravenously). Anesthesia was induced with tiletamine/zolazepam (0.7 mg kg −1 intravenously). During anesthesia, heart rate (HR), pulse quality, respiratory rate, temperature, SpO 2 , movement, and reflexes were measured every 5 minutes. Arterial blood gases were evaluated before the premedication and during the surgical procedure. The quality of induction and recovery was recorded. The sedation was appropriate, and the quality of recovery was evaluated as good. A statistically significant difference was revealed between the basal and intra-anesthesia HR. No differences were observed in blood gas parameters during the procedure. The results suggested that general anesthesia produced with tiletamine/zolazepam for induction in horses sedated with medetomidine is suitable during orchiectomy under field conditions. [ABSTRACT FROM AUTHOR]

Fungal infections are a global health problem with high mortality and morbidity rates. Available antifungal agents have high toxicity and pharmacodynamic and pharmacokinetic limitations. Moreover, the increased incidence of antifungal-resistant isolates and the emergence of intrinsically resistant species raise concerns about seeking alternatives for efficient antifungal therapy. In this context, we review literature data addressing the potential action of miltefosine (MFS), an anti- Leishmania and anticancer agent, as a repositioning drug for antifungal treatment. Here, we highlight the in vitro and in vivo data, MFS possible mechanisms of action, case reports, and nanocarrier-mediated MFS delivery, focusing on fungal infection therapy. Finally, many studies have demonstrated the promising antifungal action of MFS in vitro , but there is little or no data on antifungal activity in vertebrate animal models and clinical trials, so have a need to develop more research for the repositioning of MFS as an antifungal therapy. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is responsible for a growing subset of oropharyngeal squamous cell carcinomas (OPSCCs) in the United States and abroad. At the time of the primary diagnosis, HPV-positive tumor status is associated with improved response to chemo-radiation, progression-free survival, and overall survival. Patients with HPV-related cancer look very different than the prototypic patient with tobacco-related SCC of the oral cavity. They tend to be white males that are younger, of higher socioeconomic status, and more highly educated. Moreover, they are often non-smokers who do not abuse alcohol. HPV-related SCC has a strong predilection for the oropharynx, particularly the lingual and palatine tonsils. HPV-16 genotype is the most common genotype, accounting for up to 92% of HPV-positive oropharyngeal squamous cell carcinomas. The need for routine HPV testing of oropharyngeal carcinomas is urgent and compelling. First, HPV status is a powerful indicator of patient prognosis. HPV positivity correlates with a lower risk of tumor progression and death, reflecting in part an enhanced sensitivity to ionizing radiation with or without chemotherapy. In our understanding, HPV status, which is easily acquired with routine investigations, should be included in the standard operational procedures for the diagnosis and treatment of head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Résumé L’abus de substances psychoactives (SPA) s’est diversifié ces dernières années, tant au niveau des populations concernées que des produits consommés. Si la dépendance et les troubles psychiatriques liés à la consommation de ces substances sont généralement connus, les complications somatiques, en particulier uro-néphrologiques, le sont moins. Nous proposons tout d’abord dans cette revue un état des lieux des SPA consommées par les usagers de drogue en France, à partir des données de l’étude nationale pharmaco-épidémiologique OPPIDUM (Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse). Parmi les 5003 patients interrogés, 84 % étaient consommateurs d’au moins une SPA médicamenteuse, avec des indicateurs d’abus dans 28 % des cas, et plus de la moitié avaient consommé une SPA non médicamenteuse (principalement du cannabis) la semaine précédente. Nous décrivons ensuite les complications urologiques et néphrologiques des principales SPA, telles que l’héroïne, la cocaïne, le cannabis, l’ecstasy, le LSD, les amphétamines, les nouveaux produits de synthèse, la kétamine et les médicaments de substitution aux opiacés. Nous présentons enfin une enquête pharmaco-épidémiologique concernant les patients hospitalisés en néphrologie adulte au CHU de Marseille pour des complications liées à l’abus de SPA. Entre 2000 et 2015, 22 patients âgés de 18 à 57 ans ont été hospitalisés pour des complications néphrologiques des SPA, telles que glomérulonéphrite aiguë, hyalinose segmentaire et focale, insuffisance rénale aiguë ou chronique. Les complications somatiques liées à l’usage des SPA participent à leur dangerosité et peuvent avoir une valeur d’alerte. Il est important que les professionnels de santé signalent au centre d’addictovigilance de leur territoire les complications sanitaires liées à l’usage des SPA, afin d’optimiser l’information donnée aux patients et aux professionnels de santé et d’adapter des programmes de prévention et de réduction des risques. A great diversification of drugs of abuse has been observed in recent years, both in the populations using them and in the types of drugs. Although dependency and psychiatric disorders associated with the abuse of these substances is well known, somatic complications, uro-nephrotoxicity in particular, are less recognized. We propose here an overview of the products used by drugs abusers in France, through the analysis of the national pharmaco-epidemiological study Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse (OPPIDUM). Among the 5003 patients who participated in this survey, 84% were on prescribed psychoactive substances, with indicators of abuse in 28% of cases; more than half of these patients had also been using drugs of abuse (mainly cannabis) in the previous week. We then describe the main urological and renal toxicities of these drugs, in particular of heroin, cocaine, cannabis, ecstasy, LSD, amphetamine, new designer drugs, ketamine and opiate substitution treatment. We finally present a pharmaco-epidemiological survey of patients hospitalized for drugs complications in nephrology at the university hospital of Marseille. Between 2000 and 2015, 22 patients aged 18 to 57 years were hospitalized for renal adverse effects of drugs of abuse, such as glomerulonephritides, focal segmental glomerulosclerosis, acute kidney injury or chronic kidney disease. The somatic complications of drugs participate in their dangerousness and should be a red flag. They should be systematically reported to the addictovigilance national network to allow the improvement of information given to the patients and the medical community, and to adapt the prevention and risk reduction policies. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this paper is to describe epidemiology and clinical manifestations of oral infection by Human papillomavirus (HPV), with particular attention to potential malignant lesions. Materials and methods. A systematic review of the literature was conducted to describe the state of the art about HPV infection in oropharyngeal mucosa and its modalities of transmission, with particular attention to possible simultaneous infection in multiple anatomic sites. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. Therapeutic protocols are also described where necessary. Results. In recent years there has been a growing interest in HPV oral medicine, suggesting a role of such a family of viruses in the development of neoplasms of the oropharyngeal district as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (e.g. genital, anal and oral). Conclusions. Recent studies about HPV infection are a basic requirement in order to promote the health of patients and provide them with the most exhaustive indications from dentists. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to describe the use of simple interrupted suture pattern for the closure of the abdomen after ventral midline celiotomy in horses and to evaluate the prevalence of resulting incisional complications. Seventy horses undergoing abdominal surgery (2006–2015) and surviving at least 30 days were included in the study. Closure technique of the abdominal wall was performed on three layers. Linea alba was closed with a simple interrupted pattern using number two coated braided absorbable polyglycolic acid suture. Follow-up information was recovered at the 90th day postoperatively. Incisional complications considered included drainage, infection, dehiscence, and herniation. The complications observed in the present study using simple interrupted suture pattern were 4.29% (3 of 70), lower than reported in literature with different suture pattern. Simple interrupted suture pattern could be a valid option for the closure of linea alba after ventral midline celiotomy in horses. [ABSTRACT FROM AUTHOR]

Recent reports accounted for the intraarticular (IA) use of the stanozolol in the horse as a disease-modifying drug without any previous specific indication concerning the minimal dosage effective in the horse, avoiding or limiting anabolic consequences. The objective was (1) to evaluate possible adverse reactions after IA administration of three different dosages (1, 2.5, and 5 mg) of stanozolol in metacarpophalangeal joints of lame horses; (2) to evaluate its clinical and pharmacologic effects; and (3) to find out the minimal drug dose that can produce a one grade reduction of lameness in the American Association of Equine Practitioner (AAEP) lameness scale in at least 80% of the treated animals. Twenty-four horses with acute lameness of 2/5° (AAEP scale) due to osteoarthritis of the fetlock joint were included in the study. The animals were randomly divided in four groups that received every 7 days placebo or 1, 2.5, and 5 mg of stanozolol, respectively, until a one grade decrease of lameness was reached. No noticeable adverse reactions were observed. In two horses of six (33.3%), grouped in stanozolol 1 mg (STN 1), 2.5 mg (STN 2.5), and 5 mg (STN 5), the lameness score decreased after the first injection. During the evaluation after the second injection, five horses of six (83.33%) in the group STN 5 showed reduced or no lameness, whereas the reduction in lameness observed in the STN 1 and STN 2.5 groups was in four of six (66.6%). In conclusion, two IA treatments with 5 mg of stanozolol produce a reduction of one grade lameness in early osteoarthritis in horses. [ABSTRACT FROM AUTHOR]

The study clinically evaluated the effectiveness of autologous platelet-rich plasma (PRP), obtained using a double transfusion bag after an ultrasound-guided intralesion injection into an acute lesion of proximal portion of suspensory ligament (SL). Twenty horses with acute proximal suspensory ligament desmitis were included in the study. An ultrasound evaluation of the proximal region of the SL was carried out, and the cross-sectional area (CSA) percentage and fiber score alignment were determined. Four hundred fifty milliliters of blood was collected, and PRP was obtained by means of the buffy coat method, using a double transfusion bag. The PRP was injected into the lesion using an ultrasound guide. A long-term follow-up was carried out by means of a telephonic interview with the owner. The median CSA of the SL lesion at the first examination was 30%. The median platelet count in the PRP was 1,045 × 10 3 platelets/μL; the final concentration ranged from six to 20 times higher than the platelet blood count. Sixteen horses returned to activity within a period ranging from 12 to 24 weeks from the last PRP injection, and four animals recidivated in different regions of suspensory ligament: midbody desmitis and medial branch. Clinical results confirm that the use of autologous PRP supports healing and reduces recurrence in acute SL lesions. [ABSTRACT FROM AUTHOR]

The aim of the present work was to isolate, cultivate, differentiate, and conduct cellular characterization of mesenchymal stem cells (MSCs) derived from equine adipose tissue (eAT) and bone marrow (eBM). Isolated and characterized cells were used in racehorses suffering from a superficial flexor tendon injury. Equine adipose tissue collection was performed at the base of the horse tail, whereas eBM was aspirated from iliac crest. Mononuclear cell fraction was isolated and cultured. In vitro differentiation and molecular characterization at P3 of culture were performed. No statistically significant differences in the number of cell doublings were found among different culture passages ( P > .05). Doubling time was greater for eBM than eAT (3.2 ± 1.5 vs. 1.3 ± 0.7; P < .05). Positive von Kossa and Alizarin Red staining confirmed osteogenesis. Alcian Blue and Oil Red O staining illustrated chondrogenesis and adipogenesis, respectively. Isolated cells resulted positive for CD90, CD44, and CD105, whereas negative for hematopoietic markers, CD14, CD45, and CD34. Using isolated cells for injured tendon therapy, no adverse reactions were observed, and all inoculated horses returned to race competitions. In vitro results revealed the immunophenotypic characterization of isolated cells similar to that observed in human MSCs from the same sources; furthermore, in the present study, their clinical use proves the safety of eBM-derived and eAT-derived MSCs and a successful outcome for the treated animals that returned to their previous level of sport activity. [ABSTRACT FROM AUTHOR]

Poor data could be found in the literature on the effects of intra-articular (IA) administration of stanozolol in horses affected by osteoarthritis (OA). To verify the clinical effects of IA stanozolol in acute and chronic cases of OA in horses, a clinical double-blinded trial involving 60 client-owned horses was performed. Veterinary practitioners selected horses, all showing clinical signs of acute or chronic OA, diagnosed in a single joint. After lameness evaluation and synovial fluid collection, the clinicians administered one to four (acute cases) or one to six (chronic cases) weekly IA doses of 5 mg of stanozolol or placebo. Positive result was considered a grade 1 improvement in lameness scored according to the American Association of Equine Practitioner scale. The characteristics of the synovial fluid were also evaluated. Of the 60 horses included in the study, 31 were affected by acute OA and 29 by chronic OA. Horses were treated blindly with placebo. The overall outcomes were positive in 82.50% of cases. Lameness disappeared completely in 15 of 21 (acute) and 11 of 19 (chronic) animals, and there was a significant reduction after two and four treatments, in the acute and chronic cases, respectively. Improvement in the physical characteristics of the synovial fluid sampled was evident after the third treatment. Stanozolol injected IA at a dose of 5 mg significantly resolved lameness in affected joints. Stanozolol could be considered a safe option for the treatment of horses suffering from OA. [ABSTRACT FROM AUTHOR]

Ketoconazole (KTZ) is an antifungal agent; however, its bioavailability and therapeutic efficacy are reduced by the low aqueous solubility of the drug. Aiming at providing to improve the biopharmaceutical properties of KTZ, we studied the water-soluble different calix[ n ]arenes as carrier systems for KTZ. All calix[ n ]arene-KTZ tested showed in vitro antifungal activity superior or similar to free KTZ against Candida spp. The CX6Na/KTZ obtained by physical mixture and freeze-drying methods were the most active, decreasing KTZ concentrations required for growth inhibition against azole-resistant isolates (e.g., C. auris). Moreover, CX6Na/KTZ showed no toxic effect on Galleria mellonella larvae and the treatment of infected larvae with C. albicans and C. auris was effective at a lower dose compared with free KTZ. Thus, CX6Na/KTZ may have a potential approach to treat mycosis, especially by improvement of KTZ inhibitory activity against azole-resistant Candida. [ABSTRACT FROM AUTHOR]

A 2-year-old Quarter Horse filly was admitted to our facility with a two-day history of trauma caused by barbed wire on the front face of the right front limb fetlock joint. A septic arthritis was confirmed with the synovial fluid examination. The cytologic evaluation of synovial fluid showed 101,000 leukocytes/mm3, 90% neutrophils, and a total protein concentration of 4 g/dL. It was, therefore, decided to perform an arthroscopic lavage using an ultrasonic device with the tip inserted inside the synovial cavity to exploit the phenomenon of acoustic cavitation. After the removal of the synovial pannus, the probe was left to vibrate in the area near the visible penetrating wound inside the joint until three liters of saline was finished. Further studies are needed for understanding and applying this technology in different equine fields and with different bacterial species. However, these first results are promising for the efficacy of this innovative procedure. • A traumatic metacarpophalangeal septic arthritis was treated in a 2-year-old filly with an ultrasonic medical device. • A tip able to enter into articulation was arthroscopically used. • The use of ultrasound devices for infections is well documented in human surgery. • Sonication is a promising method to remove bacteria biofilm from articular surfaces in horses. [ABSTRACT FROM AUTHOR]

Introduction L’abus de substances psychoactives (SPA) s’est diversifié ces dernières années, tant au niveau de la population qu’au niveau des produits consommés. Si les effets psychiatriques sont bien connus, les complications somatiques, et notamment uronéphrologiques, le sont peu. Matériels et méthodes Nous décrivons tout d’abord les complications urologiques et néphrologiques des principales SPA. Nous proposons ensuite un état des lieux des SPA consommées par les usagers de drogue en France à partir des données de l’étude nationale pharmacoépidémiologique Observation des produits psychotropes illicites ou détournés de leur utilisation médicamenteuse (OPPIDUM). Nous présentons enfin une enquête pharmacoépidémiologique concernant les patients hospitalisés en néphrologie adulte au CHU de Marseille pour des complications liées à l’abus de SPA entre 2000 et 2015. Résultats Selon l’étude OPPIDUM en 2014, plus de la moitié des 5003 patients interrogés avaient consommé une SPA non médicamenteuse (principalement du cannabis) la semaine précédente. Cette consommation de SPA peut entraîner de multiples atteintes rénales, avec des manifestations aiguës comme chroniques. Dans le centre de néphrologie de Marseille, 22 patients âgés de 18 à 57 ans ont été hospitalisés entre 2000 et 2015 pour des complications néphrologiques des SPA. Discussion et conclusion Les complications somatiques liées à l’usage des SPA sont variées et insuffisamment connues, responsables d’un sous-diagnostique. Il est important que les professionnels de santé signalent au centre d’addictovigilance de leur territoire les complications sanitaires liées à l’usage des SPA, afin d’optimiser l’information donnée aux patients et aux professionnels de santé et d’adapter des programmes de prévention et de réduction des risques. [ABSTRACT FROM AUTHOR]