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1.
J Hand Microsurg ; 16(4): 100129, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39234371

RESUMEN

Objectives: Proximal row carpectomy is a well-accepted surgical procedure for the management of traumatic and degenerative wrist pathologies. It is routinely performed through a dorsal approach; a volar surgical access was presented in order to enable concomitant carpal tunnel release and avoid flexion limitation or disabilities caused by adhesions of the dorsal capsule and extensor tendons. We propose a modification to the volar approach, with detailed description of skin incision (reproducing the standard palmar access to the scaphoid), capsular section (beginning with a longitudinal cut radial to flexor carpi radialis tendon and prolonged transversally along the radio-lunate joint) and sequence of carpal bone removal (starting with the scaphoid rather than the lunate). Materials and methods: The patients who underwent surgical treatment with modified volar proximal row carpectomy between 1992 and 2015 were enrolled in a retrospective analysis. Results: We report postoperative improvement in both the Mayo Wrist score and total active range of motion in 38 patients, in line with the outcomes of dorsal proximal row carpectomy. Conclusions: The modified volar approach is highly recommended when better visualization and access to proximal carpal bones are needed (particularly useful for inveterate perilunate dislocations), moreover if concomitant carpal tunnel syndrome or extensor tendon pathologies are present.

2.
Int J Pharm ; 664: 124627, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39179008

RESUMEN

3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.


Asunto(s)
Liberación de Fármacos , Enoxaparina , Impresión Tridimensional , Comprimidos , Células CACO-2 , Humanos , Administración Oral , Enoxaparina/administración & dosificación , Enoxaparina/farmacocinética , Enoxaparina/química , Resinas Acrílicas/química , Animales , Ácidos Polimetacrílicos/química , Mucosa Intestinal/metabolismo , Masculino , Sistemas de Liberación de Medicamentos/métodos , Adhesividad , Permeabilidad , Polivinilos/química , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Anticoagulantes/química
3.
Molecules ; 29(16)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39202988

RESUMEN

PURPOSE: Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC-choline (SNAC-CH), SNAC-sodium (SNAC-Na), and SNAC-phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide. METHODS: The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption. RESULTS: The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption. CONCLUSIONS: The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers' molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.


Asunto(s)
Disponibilidad Biológica , Caprilatos , Péptidos Similares al Glucagón , Péptidos Similares al Glucagón/farmacocinética , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/química , Administración Oral , Animales , Caprilatos/química , Sales (Química)/química , Ratas , Masculino
4.
Foods ; 13(15)2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39123574

RESUMEN

This study investigated the antibacterial effects of S-nitroso-N-acetylcysteine (SNAC) and sodium nitrite (NaNO2) against Escherichia coli and their application in beef sausages. Both SNAC and NaNO2 demonstrated pH-responsive antibacterial activity, with SNAC showing greater efficacy than NaNO2 (p < 0.05) at the same pH (3, 5, and 7). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced in E. coli by SNAC were significantly higher than those induced by NaNO2 (p < 0.05), and both ROS and RNS values increased as the pH decreased. In addition, a lower pH led to more pores on the E. coli cell surface and increased membrane permeability, resulting in a more pronounced inhibitory effect. When applied to a beef sausage, SNAC-treated sausages had significantly lower total colony counts and carbonyl content compared to NaNO2-treated ones (p < 0.05). Consequently, SNAC shows great potential as a replacement for NaNO2 in meat products.

5.
J Hand Surg Asian Pac Vol ; 29(4): 294-301, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39005174

RESUMEN

Background: Perilunate fracture-dislocations are frequently associated with a high risk of developing post-traumatic arthritis. Current studies indicate that during mid-term follow-ups, radiological signs of arthritis do not appear to correspond with functional score. The aim of this study was to assess the occurrence of posttraumatic arthritis and the wrist function after perilunate dislocations (PLD) and fracture dislocations at a mid-term follow-up of 7 years. Methods: We report the clinical and radiological outcomes of 17 wrists treated for PLD or fracture-dislocation by open reduction and internal fixation through a dorsal approach with dorsal ligament repair. Functional outcomes were evaluated using the short version of the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), the Patient-Rated Wrist Evaluation questionnaire (PRWE) and the Mayo Wrist Score (MWS). Results of radiographs were assessed using the Herzberg Radiological Scoring Chart. Results: The MWS showed five excellent, five good, five fair and two poor results with an average score of 81%. Radiological analysis using the Herzberg classification revealed midcarpal and/or radiocarpal arthritis in 65% of cases, lunate collapse in 59% and an increase in the mean ulnar translocation ratio in 53% of the cases. Complications included one case of lunate osteonecrosis and one case of stage 3 scapholunate advanced collapse that required revision surgery. Conclusions: Although the clinical and functional outcomes are favourable at mid-term follow-up, radiological evaluation shows a progression towards osteoarthritis (OA). Further research is warranted to refine treatment strategies and investigate factors influencing the development of OA. Level of Evidence: Level IV (Therapeutic).


Asunto(s)
Fractura-Luxación , Fijación Interna de Fracturas , Hueso Semilunar , Humanos , Masculino , Femenino , Adulto , Estudios de Seguimiento , Hueso Semilunar/lesiones , Hueso Semilunar/diagnóstico por imagen , Hueso Semilunar/cirugía , Persona de Mediana Edad , Fijación Interna de Fracturas/métodos , Fractura-Luxación/cirugía , Fractura-Luxación/diagnóstico por imagen , Evaluación de la Discapacidad , Adulto Joven , Traumatismos de la Muñeca/cirugía , Traumatismos de la Muñeca/diagnóstico por imagen , Radiografía , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/cirugía , Articulación de la Muñeca/fisiopatología , Artritis/etiología , Artritis/diagnóstico por imagen , Artritis/cirugía , Reducción Abierta/métodos
6.
Injury ; 55 Suppl 1: 111350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39069341

RESUMEN

OBJECTIVES: This study aimed to assess clinical, functional and radiological outcomes after three-corner arthrodesis in patients suffering from symptomatic scapholunate or scaphoid non-union advanced collapsed wrists. We hypothesised that three-corner arthrodesis provided satisfactory clinical and radiological results in the long term. MATERIAL AND METHODS: This was a retrospective study of 13 patients (14 wrists) who underwent a three-corner arthrodesis between March 2004 and January 2019 with a mean follow-up of 6,7 years. Clinical assessment consisted of wrist motion, grip strength, pain and functional scores (Quick-DASH, PRWE, MWS). All complications and surgical revisions were investigated. Radiographic assessment searched for union, evaluated carpal height and ulnar translation, lunate tilt and occurrence of radio-lunate arthritis. RESULTS: At the last follow-up Quick-DASH and PRWE scores were 24,87(± 17.2) and 47.4 (± 26.9) respectively and were significantly improved. Wrist motion was 35°, 32°, 10° et 24° of flexion, extension, radial and ulnar deviation respectively. Union was obtained for 13 (92,9%) wrists. The mean radiolunate angle was 11° (-17°-34°). Three patients needed reintervention, which 2 consisted of total wrist arthrodesis due to persisting pain. Mild signs of radio-lunate arthritis were found in three patients. CONCLUSION: Three-corner arthrodesis seemed to provide satisfactory long-term functional outcomes. The union rate was high and even patients with signs of radio-lunate arthritis still had improved outcomes at the last follow-up. It could be a part of surgical options in wrists with radio- and midcarpal arthritis, among other procedures.


Asunto(s)
Artrodesis , Fracturas no Consolidadas , Hueso Semilunar , Radiografía , Rango del Movimiento Articular , Hueso Escafoides , Articulación de la Muñeca , Humanos , Artrodesis/métodos , Masculino , Femenino , Estudios Retrospectivos , Hueso Escafoides/cirugía , Hueso Escafoides/diagnóstico por imagen , Articulación de la Muñeca/cirugía , Articulación de la Muñeca/fisiopatología , Articulación de la Muñeca/diagnóstico por imagen , Persona de Mediana Edad , Estudios de Seguimiento , Resultado del Tratamiento , Adulto , Hueso Semilunar/cirugía , Hueso Semilunar/diagnóstico por imagen , Fracturas no Consolidadas/cirugía , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/fisiopatología , Fuerza de la Mano
7.
J Am Med Dir Assoc ; 25(8): 105072, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38857684

RESUMEN

OBJECTIVES: Previous studies demonstrated that discrepancies between subjective and objective health measures are associated with physical and mental health-related outcomes in older adults. We investigate whether such discrepancies are also associated with risk of injurious falls in community-dwelling Swedish older adults. DESIGN: A prospective, observational cohort study. SETTING AND PARTICIPANTS: Using data from the Swedish National Study on Aging and Care in Kungsholmen, we followed 2222 community-dwelling older adults aged ≥60 years at baseline, across a 10-year period of data collection (2001-2011). METHODS: A "health asymmetry" metric classified older adults into 4 categories, based on the level of agreement between their subjective and objective health scores ("health pessimist", "health optimist", "poor health realist", and "good health realist"). Time-varying Cox proportional hazard and Laplace regressions were employed to investigate if these categories were associated with the risk of injurious falls. RESULTS: Over a 10-year follow-up, 23.5% of the sample experienced an injurious fall. Health optimists had the greatest risk of experiencing an injurious fall [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.66, 2.80], compared with good health realists. Poor health realists (HR 1.77, 95% CI 1.50, 2.11) and health pessimists (HR 1.66, 95% CI 1.21, 2.29) also had an increased risk of experiencing injurious falls, compared with good health realists. Being a health pessimist was only associated with the risk of injurious falls within the younger-old (HR 2.43, 95% CI 1.63, 3.64) and among males (HR 1.95, 95% CI 1.14, 3.33). CONCLUSIONS AND IMPLICATIONS: Older adults with similar objective health levels may differ in terms of their injurious fall risk, depending on their subjective health. Interpreting subjective health alongside objective health is clinically pertinent when assessing injurious fall risk.


Asunto(s)
Accidentes por Caídas , Vida Independiente , Humanos , Accidentes por Caídas/estadística & datos numéricos , Suecia/epidemiología , Masculino , Anciano , Femenino , Estudios Prospectivos , Medición de Riesgo , Anciano de 80 o más Años , Estado de Salud , Persona de Mediana Edad , Evaluación Geriátrica/métodos , Modelos de Riesgos Proporcionales , Heridas y Lesiones/epidemiología
8.
Adv Sci (Weinh) ; 11(33): e2400843, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38884149

RESUMEN

Oral peptide delivery is trending again. Among the possible reasons are the recent approvals of two oral peptide formulations, which represent a huge stride in the field. For the first time, gastrointestinal (GI) permeation enhancers (PEs) are leveraged to overcome the main limitation of oral peptide delivery-low permeability through the intestinal epithelium. Despite some success, the application of current PEs, such as salcaprozate sodium (SNAC), sodium caprylate (C8), and sodium caprate (C10), is generally resulting in relatively low oral bioavailabilities (BAs)-even for carefully selected therapeutics. With several hundred peptide-based drugs presently in the pipeline, there is a huge unmet need for more effective PEs. Aiming to provide useful insights for the development of novel PEs, this review summarizes the biological hurdles to oral peptide delivery with special emphasis on the epithelial barrier. It describes the concepts and action modes of PEs and mentions possible new targets. It further states the benchmark that is set by current PEs, while critically assessing and evaluating emerging PEs regarding translatability, safety, and efficacy. Additionally, examples of novel PEs under preclinical and clinical evaluation and future directions are discussed.


Asunto(s)
Caprilatos , Humanos , Administración Oral , Caprilatos/metabolismo , Animales , Permeabilidad , Sistemas de Liberación de Medicamentos/métodos , Péptidos , Ácidos Decanoicos
9.
Cureus ; 16(4): e59014, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38800268

RESUMEN

Scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) represent clinical entities identified by a pattern of predictable degenerative changes. They are the most common causes of wrist arthritis. Both entities can remain asymptomatic for many years and may go undiagnosed. Diagnosis is usually confirmed through clinical examination, which reveals progressive wrist pain and instability. Radiographically, degenerative changes in the radiocarpal and midcarpal joints are present, as well as nonunion of the scaphoid fracture in SNAC. The management differs according to the stage. Particularly in this review article, we reviewed the treatment options for stage II SLAC and SNAC wrist. In addition to the well-described surgical techniques such as proximal row carpectomy and four-corner fusion, alternatives such as capitolunate arthrodesis, three-corner fusion, and soft tissue procedures like capsulodesis and tenodesis are available. Proximal row carpectomy and partial arthrodeses yield comparable results. Soft tissue procedures are viable alternatives and are preferred in younger patients to avoid early salvage operations.

10.
BMC Musculoskelet Disord ; 25(1): 38, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38183045

RESUMEN

BACKGROUND: Individuals with wrist osteoarthritis (OA) can suffer from pain, muscular weakness, and impaired motion of the wrist, which can reduce the quality of life. While there is strong evidence that all patients with OA should receive first-line treatment with education and exercises, this approach has not yet been proposed for individuals with wrist OA. Therefore, this trial aimed to evaluate the effectiveness of a first line neuromuscular joint-protective exercise therapy program compared to a training program with range of motion (ROM) exercises in patients with wrist OA. METHODS: In this randomized controlled trial (RCT), 48 patients with symptomatic and radiographically confirmed wrist OA were randomly allocated to a 12-week self-management program with either a neuromuscular joint-protective exercise therapy program (intervention group) or a training program with ROM exercises only (control group). Our primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) with secondary outcome measures of grip strength, range of wrist motion, the Numerical Pain Rating, Scale (NPRS), the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Generalized Self-Efficacy Scale (GSES). The outcome measures were evaluated by a blinded assessor at baseline and 12 weeks. Between-groups differences were analyzed using the Mann-Whitney U test and within-group differences were analyzed with the Wilcoxon signed-rank test. RESULTS: A total of 41 participants were analyzed at 12 weeks. There were no significant differences in PRWE between the groups at 12 weeks (p = 0.27). However, DASH improved significantly in the intervention group compared to the control group (p = 0.02) and NPRS on load within the intervention group (p = 0.006). The difference in DASH should be interpreted with caution since it could be due to a non-significant increase (worsening) from baseline in the control group in combination with a non-significant decrease (improvement) in the intervention group. CONCLUSIONS: This RCT showed that the novel neuromuscular joint-protective exercise therapy program was not superior in reducing pain and improving function compared to a training program with ROM exercises at 12 weeks. Future research is warranted to evaluate the effectiveness of forthcoming exercise therapy treatment programs for patients with wrist OA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 10/05/2022. https://clinicaltrials.gov .


Asunto(s)
Terapia por Ejercicio , Muñeca , Humanos , Ejercicio Físico , Extremidad Superior , Dolor
11.
New Phytol ; 241(6): 2480-2494, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38296835

RESUMEN

Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome-scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress-responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought-related genes, such as OsbZIP23. Moreover, we found that OsERF103 recruits a Su(var)3-9,enhancer of zeste and trithorax-domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103-mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought-tolerant rice cultivars.


Asunto(s)
Oryza , Oryza/metabolismo , Estrés Fisiológico/genética , Sequías , Plantas Modificadas Genéticamente/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
12.
J Wrist Surg ; 13(1): 16-23, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38264130

RESUMEN

Background Single- or bicolumn limited intercarpal fusion, also called one- or two-column fusion, has been introduced as an alternative to four-corner fusion. The rationale behind this is obtaining less need for bone grafting and consequently improving the chances of the union. Method From August 2014 to October 2020, 45 consecutive patients (15 women), with a mean age of 58.4 years (range: 35-79), have been treated for scapholunate advanced collapse or scaphoid nonunion advanced collapse wrist. In 33 cases, the surgery was performed as two-column fusion, and in 12 cases as one-column fusion. The union was determined by a computed tomography (CT) scan or X-ray follow-up studies. The pain assessments (visual analog score: 0-100), range of motion (ROM), grip strength, and Quick Disabilities of the Arm, Shoulder, and Hand score were prospectively included. Results Of 45 patients, 43 were available for the follow-up, at a mean of 35 months (range: 12-68). All patients but two achieved union at a mean of 9.5 weeks (range: 5-25 weeks). Pain diminished from 60.3 (mean) preoperatively to 16.7 (mean) postoperatively ( p = 0.0001). Grip strength slightly increased from 28.2 KgF (mean) to 29 KgF (mean) (not significantly, p = 0.86). Quick Disability of the Arm, Shoulder, and Hand score improved from 39.5 (median) before the surgery to 11 (median) after the surgery ( p = 0.0004). The postoperative ROM of 62/37 degrees (mean) were recorded for total dorsovolar/radioulnar flexions, respectively. Three patients were converted to total wrist fusion and one to total wrist arthroplasty. One had a rearthrodesis to two-column fusion, which united. Conclusion One- and two-column fusion showed significant improvement in pain and function, with minimal impairment of the grip strength on the short- to mid-term follow-up. A union rate of 95% and an acceptable complication rate were achieved, without fusing all carpals. Level of Evidence Prospective, cohort study, level III.

13.
Orthop Traumatol Surg Res ; 110(2): 103783, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38048904

RESUMEN

INTRODUCTION: Proximal row carpectomy (PRC) is one of the recommended techniques for managing wrist osteoarthritis, it implies the integrity of the lunate fossa of the radius and the proximal pole of the capitate. If PRC is not possible, it is suggested to consider combining it with a capsule interposition (such as Eaton's flap) or opting for intra- or radiocarpal arthrodesis. Another alternative is to combine capitate resurfacing with a pyrocarbon implant (RCPi®). The aims of this study was to assessed the results between proximal PRC+Eaton and those associated PRC+RCPi® for advanced wrist osteoarthritis. HYPOTHESIS: We hypothesized that there would be no differences in clinical or functional outcome between proximal row carpectomy associated with RCPI® and those associated with Eaton capsular flap. MATERIAL AND METHODS: It is a monocentric, retrospective, multi-operator study involving 83 wrists with osteoarthritis, included between January 2000 and December 2020 with a minimum follow-up period of 12 months. Thirty-nine patients underwent PRC+Eaton and 44 patients underwent RCPI® resurfacing. Data such as pain, flexion, extension and strength as well as functional scores (PRWE, Mayo and quick DASH) were collected from the patient files at the last check-up. RESULTS: Results were comparable between the two groups in terms pain (VAS), mobility (flexion and extension), strength (GRASP) and functional scores (PRWE, Mayo and quick DASH). Carpal height was better preserved in the PRC+RCPI® group, with a Youm and McMurtry index evaluated at 0.3 in the PRC+Eaton group compared to 0.4 in the PRC+RCPI® group (p-value<0.001). Radiocarpal arthrodesis was required in 16% of the PRC+Eaton group and 6.8% of the PRC+RCPI® group, with a statistically significant difference (p-value=0.023). DISCUSSION: This study reports clinical and functional results that suggest RCPI® is an interesting alternative and can be associated with proximal row carpectomy in advanced wrist osteoarthritis. LEVEL OF EVIDENCE: IV; retrospective study.


Asunto(s)
Huesos del Carpo , Osteoartritis , Humanos , Estudios Retrospectivos , Muñeca , Estudios de Seguimiento , Huesos del Carpo/diagnóstico por imagen , Huesos del Carpo/cirugía , Articulación de la Muñeca/cirugía , Osteoartritis/diagnóstico por imagen , Osteoartritis/cirugía , Artrodesis/métodos , Dolor , Rango del Movimiento Articular
14.
Int J Pharm ; 650: 123680, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38070657

RESUMEN

The permeation enhancers (PEs) sodium caprate (C10) and sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) have been utilized for the intestinal and gastric delivery of macromolecules, respectively. However, the potential of C10 for the gastric delivery of a peptide and the ability of SNAC to deliver other peptides to the stomach beyond semaglutide have not been investigated. In this study, we have developed and evaluated C10 and SNAC-containing erodible tablets for the gastricdelivery of a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP/GLP1) dual agonist peptide (LY) in cynomolgus monkeys. We also evaluated the impact of release rates on the in vivo performance of C10 and SNAC. Furthermore, we compared the oral exposure of the LY peptide and semaglutide with different proteolytic stabilities using a SNAC erodible tablet. Additionally, we investigated the mechanism of action of SNAC for improving gastric absorption of the LY peptide via tissue distribution in monkey. C10 and SNAC tablets released the peptide and PE by erosion from the tablet surface with 100 % release within 60 min at pH 6.8. Following a single oral administration to monkeys, C10 and SNAC erodible tablets at 300 mg exhibited similar LY mean absolute oral bioavailability of 5.7 % and 4.2 %, respectively. The C10 immediate release capsule (500 mg) with faster dissolution profile (10 min) showed a decrease in the LY oral bioavailability; however, a faster dissolution profile (15 min) with erodible SNAC tablet resulted in a relatively higher LY oral bioavailability compared to the slow-release erodible tablets (60 min). Using SNAC as the PE, the combination of slow-release tablet design and LY peptide with higher pepsin stability resulted in about 4-fold higher mean oral bioavailability in the monkeys than semaglutide (4.2 % vs 1.2 %, respectively). In the monkey gastric tissue, SNAC was found to reduce tight junction protein levels and increase the peptide uptake into the gastric epithelium suggesting its permeation enhancing mechanism via both paracellular and transcellular pathways. Taking these data altogether, the enhanced proteolytic stability of the LY peptide combined with the optimal erodible tablets enabled the gastric delivery of the LY peptide with a higher oral bioavailability than semaglutide.


Asunto(s)
Polipéptido Inhibidor Gástrico , Estómago , Animales , Péptido 1 Similar al Glucagón , Transporte Biológico , Receptores Acoplados a Proteínas G , Haplorrinos , Administración Oral
15.
Musculoskelet Surg ; 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038900

RESUMEN

INTRODUCTION: In advanced chronic post-traumatic wrist pathology, the goal of surgery has always been to reduce pain while trying to preserve the function of the wrist itself as much as possible; numerous interventions have been developed to achieve these goals (partial arthrodesis, 4-angle arthrodesis, the use of prosthetic implants…). PURPOSES: The purpose of the study is to evaluate outcomes and complications rate of proximal row carpectomy associated with the resurfacing capitate pyrocarbon implant (RCPI) for chronic diseases of the wrist. MATERIALS AND METHODS: A retrospective analysis of the patients operated on between June 2004 and March 2021 was performed. Pain, wrist range of motion in flexion, extension, radial and ulnar deviation and grip strength were compared preoperatively and at 1, 6, 12 and 24 months. Complications and additional procedures were recorded. RESULTS: A total of 112 patients underwent surgery for proximal row carpectomy and placement of RCPI with a mean follow-up of 6.6 years. Between the preoperative and the 2-year follow-up, a reduction in pain (VAS from 7.3 to 0.5), an increase in grip strength (from 8 to 17 kg) and an increase in ROM in all planes (flexion from 19° to 44°, extension from 20° to 46°, radial deviation from 7° to 14° and ulnar deviation from 13° to 28°) were recorded. Ten (8.9%) patients required additional surgery, with only 2 (1.8%) patients requiring revision of the implant. CONCLUSIONS: Proximal row carpectomy associated with RCPI is an excellent surgical strategy to relieve pain and to improve wrist range of motion and grip strength in patients with chronic diseases of the wrist.

16.
Plant Sci ; 337: 111894, 2023 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-37813193

RESUMEN

NAC family gene - SNAC1 (Stress-responsive NAC1) is responsive to drought, salt, cold stress, and ABA. It acts as a regulator in mediating tolerance to abiotic stress through different pathways. Abiotic stress, among them drought and salinity, are adverse factors for plant growth and crop productivity. SNAC1 was an object of high interest according to the effect of improved drought and salt tolerance when overexpressed in different plant species such as rice, wheat, barley, cotton, maize, banana, or oat. SNAC1 functions by regulating the expression of genes that contain the NAC Recognized Sequence (NACRS) within their promoter region. This gene is induced by drought, specifically in guard cells. Its downstream targets have been identified. The role of SNAC1 in molecular and physiological responses during abiotic stress has been proposed, but this knowledge still needs to be expanded. Here, we describe recent advances in understanding the action of SNAC1 in adapting plants to abiotic stress.

17.
J Hand Surg Eur Vol ; : 17531934231209872, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37903310

RESUMEN

This pragmatic randomized controlled trial compared lunocapitate fusion (LCF) and four-corner fusion (4CF) for scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) in 64 patients. The primary outcome was change in grip strength from preoperative to 1 year postoperatively. The secondary outcomes were Disability of the Hand, Arm, and Shoulder score, Patient Rated Wrist Evaluation score, EuroQol-5D-3L, range of motion, key pinch strength and complications 12 months postoperatively. Grip strength improved only to a small extent and there was no difference between the groups. No differences were found in the secondary outcomes. In conclusion, LCF is not inferior to 4CF regarding strength, range of motion or patient-reported outcome measures.Level of evidence: I.

18.
Trials ; 24(1): 628, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37784197

RESUMEN

BACKGROUND: Post-traumatic wrist osteoarthritis (OA) can eventually lead to pain, muscular weakness, and stiffness of the wrist, which can affect the function of the entire upper limb and reduce the quality of life. Although there is strong evidence that all patients with OA should be offered adequate education and exercises as a first-line treatment, an effective self-management program, including structured education and therapeutic exercises, has not yet been introduced for individuals with wrist OA. This trial aims to evaluate the effectiveness of an exercise therapy program with joint protective strategies to improve neuromuscular control (intervention group) compared to a training program with range of motion exercises (control group). METHODS: This is a single-blinded randomized controlled trial (RCT) with two treatment arms in patients with symptomatic and radiographically confirmed wrist OA. The trial will be conducted at a hand surgery department. The participants will be randomly assigned either to a neuromuscular exercise therapy program or to a training program with range of motion exercises only. Participants in both groups will receive a wrist orthosis and structured education on wrist anatomy, pathophysiology, and joint protective self-management strategies. The programs consist of home exercises that will be performed twice a day for 12 weeks. The Patient-Rated Wrist Evaluation (PRWE) is the primary outcome measure of pain and function. Wrist range of motion (ROM), grip strength, the Numeric Pain Rating scale (NPRS), Disabilities of the Arm, Shoulder, and Hand (DASH), the General Self-Efficacy Scale (GSES), Global Rating of Change (GROC), and conversion to surgery are the secondary measures of outcome. Assessments will be performed at baseline and at 3, 6, and 12 months after baseline by a blinded assessor. DISCUSSION: The upcoming results from this trial may add new knowledge about the effectiveness of a self-managed exercise therapy program on pain and function for individuals with wrist OA. If the present self-management program proves to be effective, it can redefine current treatment strategies and may be implemented in wrist OA treatment protocols. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05367817. Retrospectively registered on 27 April 2022. https://clinicaltrials.gov .


Asunto(s)
Osteoartritis de la Rodilla , Automanejo , Humanos , Osteoartritis de la Rodilla/terapia , Resultado del Tratamiento , Muñeca , Terapia por Ejercicio/efectos adversos , Terapia por Ejercicio/métodos , Dolor , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
J Orthop Surg Res ; 18(1): 681, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37705034

RESUMEN

The present study compares the postoperative clinical, radiological, and patient-reported functional results between the surgical procedures Proximal Row Carpectomy and Limited Carpal Fusion, in the treatment of SLAC and SNAC conditions of the wrist. 15 Proximal Row Carpectomy patients and 45 Limited Carpal Fusion patients were included in the study. Postoperative outcomes were assessed and compared for pain at load, range of motion, grip strength, Quick-DASH, and satisfaction. A radiological assessment was performed at the follow-up. The Proximal Row Carpectomy patients had a mean age of 60 years (range 31-77) and a mean follow-up of 42 months. The Limited Carpal Fusion patients had a mean age of 58 years (range 35-76) and a mean follow-up of 41 months. The patients treated with Limited Carpal Fusion performed significantly better regarding pain, radial-ulnar motion, and the Quick-DASH (p = 0.002, p = 0.003, and p = 0.002), respectively. The grip strength difference between the treatment groups was stratified for gender and was found significantly better for men in the LCF-treated patients, but not different for women (p = 0.03, p = 0.26), respectively. Differences in flexion-extension between the groups were insignificant (p = 0.525). A higher conversion rate to total wrist fusion was observed in the patients treated with the Proximal Row Carpectomy. All the Proximal Row Carpectomy patients had osteoarthritis at follow-up, whereas it was seen in 19% of the Limited Carpal Fusion patients. The patient-reported satisfaction was substantially better for the Limited Carpal Fusion patients. In conclusion, among patients treated for SNAC and SLAC wrist conditions, besides the findings of flexion-extension, and grip strength which were found without difference for women the findings are in favour of Limited Carpal Fusion compared to Proximal Row Carpectomy. Further, preferably prospective studies are needed to confirm or reject our findings.Level of evidence: Retrospective, comparative cohort study, level III.


Asunto(s)
Articulación de la Muñeca , Muñeca , Masculino , Humanos , Femenino , Preescolar , Niño , Estudios de Cohortes , Estudios Retrospectivos , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/cirugía , Dolor
20.
Plants (Basel) ; 12(14)2023 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-37514345

RESUMEN

Arsenic (As) is one of the toxic heavy metal pollutants found in the environment. An excess of As poses serious threats to plants and diminishes their growth and productivity. NAC transcription factors revealed a pivotal role in enhancing crops tolerance to different environmental stresses. The present study investigated, for the first time, the functional role of SNAC3 in boosting As stress tolerance and grain productivity in rice (Oryza sativa L.). Two SNAC3-overexpressing (SNAC3-OX) and two SNAC3-RNAi transgenic lines were created and validated. The wild-type and transgenic rice plants were exposed to different As stress levels (0, 25, and 50 µM). The results revealed that SNAC3 overexpression significantly improved rice tolerance to As stress and boosted grain yield traits. Under both levels of As stress (25 and 50 µM), SNAC3-OX rice lines exhibited significantly lower levels of oxidative stress biomarkers and OsCRY1b (cryptochrome 1b) expression, but they revealed increased levels of gas exchange characters, chlorophyll, osmolytes (soluble sugars, proteins, proline, phenols, and flavonoids), antioxidant enzymes (SOD, CAT, APX, and POD), and stress-tolerant genes expression (OsSOD-Cu/Zn, OsCATA, OsCATB, OsAPX2, OsLEA3, OsDREB2B, OsDREB2A, OsSNAC2, and OsSNAC1) in comparison to wild-type plants. By contrast, SNAC3 suppression (RNAi) reduced grain yield components and reversed the aforementioned measured physio-biochemical and molecular traits. Taken together, this study is the first to demonstrate that SNAC3 plays a vital role in boosting As stress resistance and grain productivity in rice through modulating antioxidants, photosynthesis, osmolyte accumulation, and stress-related genes expression, and may be a useful candidate for further genetic enhancement of stress resistance in many crops.

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