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1.
Int J Biol Macromol ; 250: 126107, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37536417

RESUMEN

Amylopectin clusters (APCs) are produced by cyclodextrin glucanotransferase (EC 2.4.1.19). Their solubility rate in aqueous solution was found to be 16.7 %. The weight-average molecular weight of APCs is ∼105 Da, as determined by multiangle laser light scattering analysis. Side chain length analysis indicated that the relative proportions of side chains with a degree of polymerization in the ranges of 2-8 and 25-50 decreased and increased, respectively, during preparation of APCs. In the exercise experiment, the blood glucose level of rats was higher in the APC-treated group than in the groups treated with commercial carbohydrate supplement (CCD) and glucose. In the forced swimming test, the swimming time in the APC and CCD groups increased by 22.6 % and 31.1 %, respectively, compared with the glucose administration group. The insulin levels were also similar between the APC and CCD groups. However, the glycogen levels in the liver and muscles of mice were significantly higher in the APC group than control group. These results suggest that APCs could potentially enhance endurance when added to sports drinks.

2.
Stem Cell Reports ; 18(4): 1030-1047, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-37044067

RESUMEN

Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10+ neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NAV1.7, NAV1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.


Asunto(s)
Neuronas , Células Madre Pluripotentes , Humanos , Neuronas/metabolismo , Nociceptores , Diferenciación Celular , Transducción de Señal , Ganglios Espinales/metabolismo , Células Receptoras Sensoriales
3.
Exp Neurol ; 364: 114393, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37003485

RESUMEN

Gain-of-function mutations in Scn9a, which encodes the peripheral sensory neuron-enriched voltage-gated sodium channel Nav1.7, cause paroxysmal extreme pain disorder (PEPD), inherited erythromelalgia (IEM), and small fiber neuropathy (SFN). Conversely, loss-of-function mutations in the gene are linked to congenital insensitivity to pain (CIP). These mutations are evidence for a link between altered sodium conductance and neuronal excitability leading to somatosensory aberrations, pain, or its loss. Our previous work in young adult mice with the Nav1.7 gain-of-function mutation, I228M, showed the expected DRG neuron hyperexcitability, but unexpectedly the mice had normal mechanical and thermal behavioral sensitivity. We now show that with aging both male and female mice with this mutation unexpectedly develop a profound insensitivity to noxious heat and cold, as well skin lesions that span the body. Electrophysiology demonstrates that, in contrast to young mice, aged I228M mouse DRGs have a profound loss of sodium conductance and changes in activation and slow inactivation dynamics, representing a loss-of-function. Through RNA sequencing we explored how these age-related changes may produce the phenotypic changes and found a striking and specific decrease in C-low threshold mechanoreceptor- (cLTMR) associated gene expression, suggesting a potential contribution of this DRG neuron subtype to Nav1.7 dysfunction phenotypes. A GOF mutation in a voltage-gated channel can therefore produce over a prolonged time, highly complex and unexpected alterations in the nervous system beyond excitability changes.


Asunto(s)
Mutación con Ganancia de Función , Canal de Sodio Activado por Voltaje NAV1.7 , Masculino , Femenino , Ratones , Animales , Mutación con Ganancia de Función/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Nocicepción , Mutación/genética , Sodio , Ganglios Espinales/patología
4.
Carbohydr Polym ; 310: 120722, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36925261

RESUMEN

To improve the applicability of quercetin (QCT), we produced a QCT and cycloamylose (CA-QCT) inclusion complex based on the cyclization activity of cyclodextrin glucanotransferase (CGTase; EC 2.4.1.19). The encapsulated QCT was purified using recycling preparative high-performance liquid chromatography, and its formation was analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The water solubility of CA-QCT was 55,000-fold higher than that of QCT. CA-QCT had 97 % stability for one week at pH 8 in a 4 °C water bath. According to a 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay, CA-QCT activity in aqueous solution was 24 times higher than that of an equal amount of QCT in aqueous solution. In an anti-inflammatory assay using lipopolysaccharide-induced RAW264.7 macrophages, CA-QCT in aqueous solution decreased nitric oxide production in a similar manner to QCT in dimethyl sulfoxide (DMSO). Additionally, even under aqueous conditions, CA-QCT more effectively inhibited the production of inflammatory mediators, such as interleukin-1ß, interleukin-6, and cyclooxygenase, compared with QCT dissolved in DMSO.


Asunto(s)
Dimetilsulfóxido , Quercetina , Quercetina/farmacología , Quercetina/química , Antiinflamatorios/farmacología , Oligosacáridos
5.
Foods ; 12(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36766169

RESUMEN

In the rice processing industry, wastewater is an inevitable by-product of rice washing. To increase the utilization of washed rice water (WRW), seven types of fermented washed rice water (FWRW) were prepared using lactic acid bacteria (LAB) and carbohydrate hydrolase. The total concentration of small maltooligosaccharides (MOSs) in the amyloglucosidase (AMG) treatment groups was about ten times higher than in the untreated groups. After 6 h of fermentation, six of the seven FWRW samples reached a pH of 4 due to the increased concentration of organic acids and could, therefore, be used as food acidity regulators. To confirm the applicability of FWRW, the traditional Korean rice cake garaetteok was prepared with FWRW and stored at 4 °C for 5 days. A texture profile analysis (TPA) revealed that the hardness of garaetteok treated with FWRW was significantly lower than that of untreated garaetteok following storage. Differential scanning calorimetry (DSC) showed that FWRW retarded the retrogradation of garaetteok during storage. The addition of FWRW using Lactobacillus reuteri with an AMG group was particularly effective for inhibiting microbial activity in garaetteok during storage. These results suggest that FWRW using AMG-added L. reuteri can be used as a novel food additive for improving the quality of traditional Korean starch foods and could also reduce the volume of waste WRW.

6.
Br J Pharmacol ; 180(8): 1148-1167, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36478100

RESUMEN

BACKGROUND AND PURPOSE: Peripheral sensitization contributes to pathological pain. While prostaglandin E2 (PGE2) and nerve growth factor (NGF) sensitize peptidergic C-nociceptors (TRPV1+), glial cell line-derived neurotrophic factor (GDNF) sensitizes non-peptidergic C-neurons (IB4+). The sigma-1 receptor (sigma-1R) is a Ca2+ -sensing chaperone known to modulate opoid analgesia. This receptor binds both to TRPV1 and the µ opioid receptor, although the functional repercussions of these physical interactions in peripheral sensitization are unknown. EXPERIMENTAL APPROACH: We tested the effects of sigma-1 antagonism on PGE2-, NGF-, and GDNF-induced mechanical and heat hyperalgesia in mice. We used immunohistochemistry to determine the presence of endomorphin-2, an endogenous µ receptor agonist, on dorsal root ganglion (DRG) neurons. Recombinant proteins were used to study the interactions between sigma-1R, µ- receptor, and TRPV1. We used calcium imaging to study the effects of sigma-1 antagonism on PGE2-induced sensitization of TRPV1+ nociceptors. KEY RESULTS: Sigma1 antagonists reversed PGE2- and NGF-induced hyperalgesia but not GDNF-induced hyperalgesia. Endomorphin-2 was detected on TRPV1+ but not on IB4+ neurons. Peripheral opioid receptor antagonism by naloxone methiodide or administration of an anti-endomorphin-2 antibody to a sensitized paw reversed the antihyperalgesia induced by sigma-1 antagonists. Sigma-1 antagonism transfers sigma-1R from TRPV1 to µ receptors, suggesting that sigma-1R participate in TRPV1-µ receptor crosstalk. Moreover, sigma-1 antagonism reversed, in a naloxone-sensitive manner, PGE2-induced sensitization of DRG neurons to the calcium flux elicited by capsaicin, the prototypic TRPV1 agonist. CONCLUSION AND IMPLICATIONS: Sigma-1 antagonism harnesses endogenous opioids produced by TRPV1+ neurons to reduce hyperalgesia by increasing µ receptor activity.


Asunto(s)
Analgesia , Nociceptores , Ratones , Animales , Nociceptores/metabolismo , Hiperalgesia/metabolismo , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacología , Factor de Crecimiento Nervioso/metabolismo , Calcio/metabolismo , Dinoprostona/metabolismo , Dolor/metabolismo , Péptidos Opioides/metabolismo , Canales Catiónicos TRPV/metabolismo , Ganglios Espinales/metabolismo , Receptor Sigma-1
7.
Elife ; 112022 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-35179483

RESUMEN

Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously expressed human Kv7.2/7.3 channels by CBD. Patch-clamp recordings showed that CBD acts at submicromolar concentrations to shift the voltage dependence of Kv7.2/7.3 channels in the hyperpolarizing direction, producing a dramatic enhancement of current at voltages near -50 mV. CBD enhanced native M-current in mouse superior cervical ganglion starting at concentrations of 30 nM and also enhanced M-current in rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD may contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.


Asunto(s)
Cannabidiol/farmacología , Canal de Potasio KCNQ2/metabolismo , Canal de Potasio KCNQ3/metabolismo , Neuronas/metabolismo , Animales , Células CHO , Cricetinae , Cricetulus , Fenómenos Electrofisiológicos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Canal de Potasio KCNQ2/genética , Canal de Potasio KCNQ3/genética , Neuronas/efectos de los fármacos , Ratas
8.
J Clin Med ; 11(3)2022 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-35159967

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the effectiveness of minimally invasive posterior mono-axial pedicle screws fixation in the treatment of thoracolumbar burst fractures. METHODS: In the present study, we analyzed 98 patients retrospectively who had thoracolumbar burst fractures without a neurological deficit. Patients were divided into two groups: mono-axial pedicle screw fixation group (n = 52) and poly-axial pedicle screw fixation group (n = 46). We collected clinical data (visual analog scale (VAS) score for back pain) and included radiographic measurements. RESULTS: Sagittal index was significantly improved at postop and last follow-up in the mono group and the poly group. The mono group was better for reducing and maintaining anterior vertebral height. For the mono group, the mean postoperative regional kyphosis correction rate was 62.31%, and correction loss was 14.18% in late follow-up. For the poly group, the mean postoperative regional kyphosis correction rate was 52.17%, and correction loss was 33.42% in late follow-up. The mono-axial pedicle screw group had a good correction rate and reduced the risks of correction loss. The mean VAS scores for back pain improved by 2.4/2.5 and 3.8/4.2 for the mono and poly groups, respectively. There was no significant difference between groups. CONCLUSIONS: The mono-axial pedicle screw fixation was better for reducing and maintaining anterior vertebral height and regional kyphosis. Therefore, the mono-axial pedicle screw is a better optional instrumentation to treat thoracolumbar vertebral fractures.

9.
Sci Transl Med ; 13(619): eabj9837, 2021 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-34757806

RESUMEN

Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic agents generally lack efficacy and may have undesirable side effects. Traditional target-based drug discovery efforts that generate compounds with selectivity for single targets have a high rate of attrition because of their poor clinical efficacy. Here, we examine the challenges associated with the current analgesic drug discovery model and review evidence in favor of stem cell­derived neuronal-based screening approaches for the identification of analgesic targets and compounds for treating diverse forms of acute and chronic pain.


Asunto(s)
Dolor Crónico , Analgésicos/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Humanos , Nociceptores
10.
Foods ; 10(10)2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34681318

RESUMEN

The use of unmodified starch in frozen foods can cause extremely undesirable textural changes after the freeze-thaw process. In this study, using cyclodextrin glucanotransferase (CGTase) and branching enzymes, an amylopectin cluster with high freeze-thaw stability was produced, and was named CBAC. It was found to have a water solubility seven times higher, and a molecular weight 77 times lower, than corn starch. According to the results of a differential scanning calorimetry (DSC) analysis, dough containing 5% CBAC lost 19% less water than a control dough after three freeze-thaw cycles. During storage for 7 days at 4 °C, bread produced using CBAC-treated dough exhibited a 14% smaller retrogradation peak and 37% less hardness than a control dough, suggesting that CBAC could be a potential candidate for clean label starch, providing high-level food stability under repeated freeze-thaw conditions.

11.
Phytomedicine ; 92: 153763, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34601222

RESUMEN

BACKGROUND: Misfolded proteins are formed in the endoplasmic reticulum (ER) due to diverse stimuli including oxidant production, calcium disturbance, and inflammatory factors. Accumulation of these non-native proteins in the ER evokes cellular stress involving the activation of unfolded protein response (UPR) and the execution of ER-associated degradation (ERAD). Naturally-occurring plant compounds are known to interfere with UPR due to their antioxidant and anti-inflammatory activities, leading to inhibition of ER stress. However, there are few studies dealing with the protective effects of natural compounds on the functionality of ERAD. PURPOSE: The current study examined whether asaronic acid enhanced ubiquitin-proteasomal degradation in J774A.1 murine macrophages exposed to 7ß-hydroxycholesterol, a risk factor for atherosclerosis. Asaronic acid (2,4,5-trimethoxybenzoic acid), identified as one of purple perilla constituents, has anti-diabetic and anti-inflammatory effects. Little is known regarding the effects of asaronic acid on the ERAD process and the ubiquitin-proteasomal degradation. METHODS AND RESULTS: Murine macrophages were incubated with 28 µM 7ß-hydroxycholesterol in absence and presence of 1-20 µΜ asaronic acid for up to 24 h. Nontoxic asaronic acid in macrophage diminished the activation of the ER stress sensors of ATF6, IRE1 and PERK stimulated by 7ß-hydroxycholesterol. This methoxybenzoic acid down-regulated the oxysterol-induced expression of EDEM1, OS9, Sel1L-Hrd1 and p97/VCP1, all required for the recognition, recruitment and dislocation of misfolded proteins. On the other hand, asaronic acid enhanced the ubiquitin-proteasomal degradation of non-native proteins dislocated to the cytosol by 7ß-hydroxycholesterol, which entailed the induction of the chaperones of Hsp70 and CHIP and the increased colocalization of ubiquitin and proteasomes. Taken together, asaronic acid attenuated the induction of the UPR-associated sensors and the dislocation-linked transmembrane components in the ER. Conversely, this compound enhanced the proteasomal degradation of dislocated non-native proteins in concert with the chaperones of Hsp70 and CHIP through ubiquitination. CONCLUSION: These observations demonstrate that asaronic acid may be a potent atheroprotective agent as a natural chaperone targeting ER stress-associated macrophage injury.


Asunto(s)
Hidroxicolesteroles , Ubiquitina , Animales , Estrés del Retículo Endoplásmico , Degradación Asociada con el Retículo Endoplásmico , Macrófagos , Ratones
12.
Artículo en Inglés | MEDLINE | ID: mdl-34527066

RESUMEN

Pueraria lobata (Willd.) Ohwi, known as kudzu, is one of the most popular traditional medicines in Asian countries. It has been widely used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms. This study aimed to investigate the estrogenic effect of P. lobata extract (PE) against postmenopausal osteoporosis in ovariectomized (OVX) rats. OVX rats were treated with PE (25-1600 mg/kg) for 8 weeks. Biochemical parameters, estradiol, and bone turnover markers (e.g., osteocalcin, C-terminal telopeptide fragment of type I collagen, deoxypyridinoline, and pyridinoline) were measured in plasma samples. In addition, estrogen receptor-alpha (ER-α) protein expression and morphology of uterine were evaluated. Long-term treatment with PE did not cause liver damage in OVX rats. PE supplementation reduced body weight gain in obese rats with high lipid accumulation induced by ovariectomy. Furthermore, PE exhibited a protective effect against insulin resistance, hyperlipidemia, and hepatic lipid peroxidation. PE treatment increased uterine weight and thickness of the uterine layers in cases of uterus atrophy due to removal of ovaries. The levels of bone turnover markers, which were significantly increased in OVX rats, were decreased by PE treatment. Western blotting analysis showed that ER-α protein expression was upregulated in PE-treated rats compared with OVX rats. These results suggest that PE could be a promising alternative functional food for improving menopausal symptoms.

13.
J Clin Med ; 10(16)2021 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-34442022

RESUMEN

The suture button (SB) device was introduced to negate the need for routine hardware removal in the treatment of syndesmosis injuries. However, a considerable SB removal rate has been reported, and the impact of removal is unknown. This study aimed to evaluate the radiographic and clinical outcomes after removal of SB for syndesmosis fixation. A total of 36 patients who underwent removal surgery after syndesmosis fixation using SB were identified. The mean postoperative time to removal was 12.2 months. On a plain radiograph, tibiofibular clear space (TFCS) was measured and compared at three follow-up time points. In patients with computed tomography (CT) imaging (n = 18), the anterior-to-posterior (A/P) ratio was measured to evaluate changes in quality of reduction. Additionally, clinical outcomes were assessed. There were no significant differences in TFCS between the three follow-up periods. None of the patients exhibited recurrent diastasis after SB removal. Although CT analysis demonstrated malreduction in six patients (33.3%), five of six patients had a subsequent spontaneous reduction of the syndesmosis. Clinically, all patients described the resolution of symptoms related to painful hardware at the final follow-up. Our results demonstrate that SB removal at one year following syndesmosis fixation leads to improved clinical symptoms without negatively impacting the quality of syndesmosis reduction.

14.
Br J Pharmacol ; 178(19): 3905-3923, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33988876

RESUMEN

BACKGROUND AND PURPOSE: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough. EXPERIMENTAL APPROACH: We tested the ability of BW-031 to inhibit pain in three models of tissue inflammation:- inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. KEY RESULTS: BW-031 inhibited Nav 1.7 and Nav 1.1 channels with approximately sixfold greater potency than QX-314 when introduced inside cells. BW-031 inhibited inflammatory pain in all three models tested, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was effective in reducing cough counts by 78%-90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization. CONCLUSION AND IMPLICATIONS: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW-031 can also effectively inhibit cough in a guinea pig model of citric acid-induced cough, suggesting a new clinical approach to treating cough.


Asunto(s)
Tos , Bloqueadores de los Canales de Sodio , Animales , Tos/inducido químicamente , Tos/tratamiento farmacológico , Cobayas , Ratones , Nociceptores , Dolor/tratamiento farmacológico , Ratas , Bloqueadores de los Canales de Sodio/farmacología , Bloqueadores de los Canales de Sodio/uso terapéutico , Canales Catiónicos TRPV
15.
Int J Mol Sci ; 22(7)2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33916310

RESUMEN

Epidemiological evidence shows that smoking causes a thrombophilic milieu that may play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD) as well as pulmonary thromboembolism. The increased nicotine level induces a prothrombotic status and abnormal blood coagulation in smokers. Since several anticoagulants increase bleeding risk, alternative therapies need to be identified to protect against thrombosis without affecting hemostasis. Astragalin is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities of antioxidant and anti-inflammation. The current study investigated that astragalin attenuated smoking-induced pulmonary thrombosis and alveolar inflammation. In addition, it was explored that molecular links between thrombosis and inflammation entailed protease-activated receptor (PAR) activation and oxidative stress-responsive mitogen-activated protein kinase (MAPK)-signaling. BALB/c mice were orally administrated with 10-20 mg/kg astragalin and exposed to cigarette smoke for 8 weeks. For the in vitro study, 10 U/mL thrombin was added to alveolar epithelial A549 cells in the presence of 1-20 µM astragalin. The cigarette smoking-induced the expression of PAR-1 and PAR-2 in lung tissues, which was attenuated by the administration of ≥10 mg/kg astragalin. The oral supplementation of ≥10 mg/kg astragalin to cigarette smoke-challenged mice attenuated the protein induction of urokinase plasminogen activator, plasminogen activator inhibitor-1and tissue factor, and instead enhanced the induction of tissue plasminogen activator in lung tissues. The astragalin treatment alleviated cigarette smoke-induced lung emphysema and pulmonary thrombosis. Astragalin caused lymphocytosis and neutrophilia in bronchoalveolar lavage fluid due to cigarette smoke but curtailed infiltration of neutrophils and macrophages in airways. Furthermore, this compound retarded thrombin-induced activation of PAR proteins and expression of inflammatory mediators in alveolar cells. Treating astragalin interrupted PAR proteins-activated reactive oxygen species production and MAPK signaling leading to alveolar inflammation. Accordingly, astragalin may interrupt the smoking-induced oxidative stress-MAPK signaling-inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism.


Asunto(s)
Quempferoles/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Embolia Pulmonar/prevención & control , Enfisema Pulmonar/prevención & control , Receptores Proteinasa-Activados/antagonistas & inhibidores , Animales , Fumar Cigarrillos/efectos adversos , Evaluación Preclínica de Medicamentos , Quempferoles/farmacología , Masculino , Ratones Endogámicos BALB C , Estrés Oxidativo , Embolia Pulmonar/etiología
16.
Food Chem ; 345: 128777, 2021 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-33321347

RESUMEN

Cyclodextrin glucanotransferase (CGTase; EC 2.4.1.19) produces cycloamyloses (CAs), which are large cyclic glucans, and subsequently transforms them to α-, ß-, and γ-cyclodextrins. We developed a novel encapsulation process based on the cyclization activity of CGTase and applied it to the formation of CA inclusion complexes with resveratrol (RVT), which has limited bioavailability due to its low water solubility. The encapsulated RVT (CA-RVT) was purified using preparative high-performance liquid chromatography. The water solubility of CA-RVT was 6,000-fold higher than that of RVT. CA-RVT in water demonstrated 98% stability for 1 week at 4 °C. According to radical scavenging activity and anti-inflammatory assays, CA-RVT in aqueous solution exhibited similar activities as an equal amount of RVT in dimethyl sulfoxide, suggesting the limited solubility of RVT can be overcome through CA encapsulation by CGTase, thus enhancing its nutraceutical value as a functional ingredient in the food industry.


Asunto(s)
Ciclodextrinas/química , Glucosiltransferasas/metabolismo , Resveratrol/química , Cápsulas , Ciclización , Ciclodextrinas/metabolismo , Solubilidad , Agua/química
17.
Pain ; 162(6): 1758-1770, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33323889

RESUMEN

ABSTRACT: Small-fiber neuropathy (SFN), characterized by distal unmyelinated or thinly myelinated fiber loss, produces a combination of sensory dysfunction and neuropathic pain. Gain-of-function variants in the sodium channel Nav1.7 that produce dorsal root ganglion (DRG) neuron hyperexcitability are present in 5% to 10% of patients with idiopathic painful SFN. We created 2 independent knock-in mouse lines carrying the Nav1.7 I228M gain-of-function variant, found in idiopathic SFN. Whole-cell patch-clamp and multielectrode array recordings show that Nav1.7 I228M knock-in DRG neurons are hyperexcitable compared with wild-type littermate-control neurons, but despite this, Nav1.7 I228M mice do not display mechanical or thermal hyperalgesia or intraepidermal nerve fiber loss in vivo. Therefore, although these 2 Nav1.7 I228M knock-in mouse lines recapitulate the DRG neuron hyperexcitability associated with gain-of-function mutations in Nav1.7, they do not recapitulate the pain or neuropathy phenotypes seen in patients. We suggest that the relationship between hyperexcitability in sensory neurons and the pain experienced by these patients may be more complex than previously appreciated and highlights the challenges in modelling channelopathy pain disorders in mice.


Asunto(s)
Ganglios Espinales , Canal de Sodio Activado por Voltaje NAV1.7 , Animales , Mutación con Ganancia de Función , Humanos , Ratones , Canal de Sodio Activado por Voltaje NAV1.7/genética , Fenotipo , Células Receptoras Sensoriales
18.
Knee Surg Sports Traumatol Arthrosc ; 29(12): 4022-4031, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32975624

RESUMEN

PURPOSE: Suprascapular nerve block (SSNB) is the most commonly used block for the relief of postoperative pain from arthroscopic rotator cuff repair and can be used in combination with axillary nerve block (ANB). Dexmedetomidine (DEX) is a type of alpha agonist that can elongate the duration of regional block. The aim of this study was to compare the effects of the use of dexmedetomidine combined with SSNB and ANB with those of the use of SSNB and ANB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Forty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single-center, double-blinded randomized controlled trial study. Twenty patients were randomly allocated to group 1 and received ultrasound-guided SSNB and ANB using a mixture of 0.5 ml (50 µg) of DEX and 9.5 ml of 0.75% ropivacaine preemptively. The other 20 patients were allocated to group 2 and underwent ultrasound-guided SSNB and ANB alone using a mixture of 0.5 ml of normal saline and 9.5 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were postoperatively checked within 48 h. The plasma interleukin (IL)-6, IL-8, IL-1ß, cortisol, and serotonin levels were also postoperatively measured within 48 h. RESULTS: Group 1 showed a significantly lower mean VAS (visual analog scale of pain) score 1, 3, 6, 12, 18 and 24 h after operation, and a significantly higher mean SAT (patient satisfaction) score 1, 3, 6, 12, 18, 24 and 36 h after the operation than group 2. Group 1 showed a significantly lower mean plasma IL-8 level 1 and 48 h after the operation, and a significantly lower mean IL-1ß level 48 h after the operation than group 2. Group 1 showed a significantly lower mean plasma serotonin level 12 h after the operation than group 2. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (36 h > 23 h, p = 0.007). Six patients each in groups 1 and 2 showed rebound pain. The others did not show rebound pain. CONCLUSIONS: Ultrasound-guided SSNA and ANB with DEX during arthroscopic rotator cuff repair resulted in a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h after the operation than SSNB and ANB alone. Additionally, SSNB and ANB with DEX tended to result in a later mean timing of rebound pain accompanied by significant changes in IL-8, IL-1ß, and serotonin levels within 48 h after the operation. The present study could provide the basis for selecting objective parameters of postoperative pain in deciding the optimal use of medication for relieving pain. LEVEL OF EVIDENCE: Level I. TRIAL REGISTRATION: 2015-20, ClinicalTrials.gov Identifier: NCT04398589. IRB NUMBER: 2015-20, Hallym University Chuncheon Sacred Heart Hospital.


Asunto(s)
Dexmedetomidina , Bloqueo Nervioso , Lesiones del Manguito de los Rotadores , Anestésicos Locales , Artroscopía , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/cirugía , Resultado del Tratamiento
19.
Arch Orthop Trauma Surg ; 141(3): 477-488, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33184700

RESUMEN

PURPOSE: Few large-scale studies using adjusted data from national registries have explored the risk factors of subsequent revision in patients with unicompartmental knee arthroplasty (UKA) compared to those with total knee arthroplasty (TKA). We investigated the incidence rate and risk factors of subsequent revision in patients with UKA and TKA. METHODS: We enrolled all patients who had undergone TKA or UKA as the primary surgical procedure without histories of having undergone either procedure during the preceding 2 years. Matched Cox regression models were used to compare the risks of revision between groups after propensity score matching. Revision was defined as conversion to revision TKA after primary TKA and conversion to TKA after UKA. RESULTS: The study enrolled 418,806 TKA patients and 446,009 UKA patients. The risk of revision during the entire study period was higher for patients with UKA than for patients with TKA (adjusted hazard ratio [HR] 1.22, 95% confidence interval [95% CI]: 1.10-1.36). The Kaplan-Meier 8-year survival was 98.7% in the TKA group and 96.7% in the UKA group. Patients with UKA were at an increased risk of revision in cases of advanced age (70-79 years, HR 1.40, 95% CI: 1.15-1.71), female sex (HR 1.32, 95% CI: 1.16-1.49), the presence of chronic obstructive pulmonary disease (COPD) (HR 1.27, 95% CI: 1.05-1.54), the presence of peptic ulcer disease (PUD) (HR 1.34, 95% CI: 1.11-1.61) compared to patients with TKA. In patients with hemiplegia, however, UKA were associated with a lower risk of subsequent revision (HR 0.25, 95% CI: 0.07-0.94). CONCLUSION: The risk of a complete exchange or failure was higher for patients with UKA than for patients with TKA. The most significant independent risk factors for subsequent a complete exchange or failure in patients with UKA were advanced age (70-79 years), female sex, and the presence of comorbidities such as COPD and PUD.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Anciano , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/mortalidad , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Falla de Prótesis , Reoperación/estadística & datos numéricos , República de Corea , Factores de Riesgo
20.
Food Sci Biotechnol ; 29(5): 667-674, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32419965

RESUMEN

To determine the physiochemical properties of the 4-α-glucanotransferase from Bifidobacterium sp., the bllj_0114 gene encoding 4-α-glucanotransferase was cloned from Bifidobacterium longum subsp. longum JCM 1217 and expressed in Escherichia coli. The amino acid sequence alignment indicated that the recombinant protein, named BL-αGTase, belongs to the glycoside hydrolase (GH) family 77. BL-αGTase was purified using nickel-nitrilotriacetic acid affinity chromatography and characterized using various substrates. The enzyme catalyzed the disproportionation activity, which transfers a glucosyl unit from oligosaccharides to acceptor molecules, and had the highest activity at 40 °C and pH 6.0. In the presence of 5 mM metal ions, in particular Cu2+, Zn2+, and Fe2+, BL-αGTase activity was reduced. To determine whether BL-αGTase can be used to generate thermoreversible gels, potato starch was treated with BL-αGTase for various reaction times. The BL-αGTase-treated starches showed sol-gel reversibility and melted at 59.6-75.7 °C.

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