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1.
Int J Nanomedicine ; 18: 1659-1676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020688

RESUMO

Introduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques. Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases. Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22. Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.


Assuntos
Canais de Cálcio , Ouro , Nanopartículas Metálicas , Caenorhabditis elegans , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/química , Ouro/efeitos adversos , Ouro/química , Canais de Cálcio/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Animais , Sensação/efeitos dos fármacos
2.
Molecules ; 27(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35164210

RESUMO

Color is an important characteristic of food products. This characteristic is related to consumer acceptability. To use the entire rhizome of Curcuma longa (CL) as a food colorant, a novel gel alike stable suspension (CLS) was previously developed using cellulose nanofibers (CNFs). Therefore, the present study was conducted to evaluate the CLS as a color additive on a stirred yogurt. Three concentrations of CLS were studied (0.1, 0.125, and 0.15 wt. %) and compared to yogurt without CLS. The obtained yogurts were characterized through the determination of pH, titratable acidity, syneresis, color and curcumin content after 1, 7, 14, and 21 days of storage. Additionally, rheological and sensory measurements were performed on the samples after one day of storage. Results show that the addition of CLS does not affect the pH and titratable acidity of the samples, but all the yogurts showed an increase in their syneresis during the storage time, showing a breakdown of the gel structure. Furthermore, the CLS suspension has the ability to impart a yellow color to yogurts, a characteristic that was stable during storage. Finally, the addition of 1 wt. % or 1.25 wt. % of CLS allows the development of a yogurt with adequate sensory perception.


Assuntos
Corantes/farmacologia , Curcuma/química , Manipulação de Alimentos/métodos , Extratos Vegetais/farmacologia , Sensação/efeitos dos fármacos , Paladar/efeitos dos fármacos , Iogurte/análise , Humanos , Reologia
3.
Nutrients ; 13(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684314

RESUMO

Prolonged exercise in the heat elicits a number of physiological changes as glycogen stores are low and water and electrolytes are lost through sweat. However, it is unclear whether these changes provoke an increase in liking of saltiness and, therefore, palatability of an oral rehydration solution (ORS). Twenty-seven recreationally active participants (n = 13 males; n = 14 females) completed sensory analysis of an ORS, a traditional sports drink (TS), and a flavored water placebo (PL) at rest and during 60 min (3 × 20-min bouts) of cycling exercise at 70% age-predicted maximum heart rate (HRmax) at 35.3 ± 1.4 °C and 41 ± 6% relative humidity. Before and after every 20 min of exercise, drinks were rated (using 20-mL beverage samples) based on liking of sweetness, liking of saltiness, thirst-quenching ability, and overall liking on a nine-point hedonic scale. Hydration status was assessed by changes in semi-nude body mass, saliva osmolality (SOsm), and saliva total protein concentration (SPC). After 60 min of exercise, participants lost 1.36 ± 0.39% (mean ± SD) of body mass and there were increases in SOsm and SPC. At all time points, liking of sweetness, saltiness, thirst-quenching ability, and overall liking was higher for the TS and PL compared to the ORS (p < 0.05). However, the saltiness liking and thirst-quenching ability of the ORS increased after 60 min of exercise compared to before exercise (p < 0.05). There was also a change in predictors of overall liking with pre-exercise ratings mostly determined by liking of sweetness, saltiness, and thirst-quenching ability (p < 0.001), whereas only liking of saltiness predicted overall liking post-exercise (R2 = 0.751; p < 0.001). There appears to be a hedonic shift during exercise in which the perception of saltiness becomes the most important predictor of overall liking. This finding supports the potential use of an ORS as a valuable means of hydration during the latter stages of prolonged and/or intense exercise in the heat.


Assuntos
Exercício Físico/fisiologia , Temperatura Alta , Percepção , Soluções para Reidratação/administração & dosagem , Soluções para Reidratação/farmacologia , Sensação , Administração Oral , Adulto , Feminino , Humanos , Masculino , Percepção/efeitos dos fármacos , Sensação/efeitos dos fármacos , Paladar/efeitos dos fármacos , Paladar/fisiologia , Sede/efeitos dos fármacos , Sede/fisiologia
4.
Biomed Res Int ; 2021: 7300098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568494

RESUMO

This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G'/G " = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R 2 = 0.923-0.989), indicating the drug diffusion from hydrogels to the medium. RVC-PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.


Assuntos
Anestesia Local , Materiais Biocompatíveis/química , Hidrogéis/química , Poloxâmero/química , Ropivacaina/farmacologia , Células 3T3 , Analgesia , Animais , Área Sob a Curva , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Elasticidade , Masculino , Camundongos , Micelas , Ratos Wistar , Reologia , Nervo Isquiático/efeitos dos fármacos , Sensação/efeitos dos fármacos , Viscosidade
5.
Cell Rep ; 36(1): 109334, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34233184

RESUMO

Persistent senescent cells (SCs) are known to underlie aging-related chronic disorders, but it is now recognized that SCs may be at the center of tissue remodeling events, namely during development or organ repair. In this study, we show that two distinct senescence profiles are induced in the context of a spinal cord injury between the regenerative zebrafish and the scarring mouse. Whereas induced SCs in zebrafish are progressively cleared out, they accumulate over time in mice. Depletion of SCs in spinal-cord-injured mice, with different senolytic drugs, improves locomotor, sensory, and bladder functions. This functional recovery is associated with improved myelin sparing, reduced fibrotic scar, and attenuated inflammation, which correlate with a decreased secretion of pro-fibrotic and pro-inflammatory factors. Targeting SCs is a promising therapeutic strategy not only for spinal cord injuries but potentially for other organs that lack regenerative competence.


Assuntos
Senescência Celular , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Compostos de Anilina/administração & dosagem , Compostos de Anilina/farmacologia , Animais , Contagem de Células , Senescência Celular/efeitos dos fármacos , Cicatriz/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Fibrose , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Bainha de Mielina/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Senoterapia/administração & dosagem , Senoterapia/farmacologia , Sensação/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Substância Branca/efeitos dos fármacos , Substância Branca/patologia , Substância Branca/fisiopatologia , Peixe-Zebra
6.
Nat Commun ; 12(1): 2074, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824316

RESUMO

Thiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed in Trpa1 knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.


Assuntos
Medo/fisiologia , Hipotermia/metabolismo , Hipóxia/metabolismo , Canal de Cátion TRPA1/metabolismo , Tiazóis/farmacologia , Animais , Bradicardia/patologia , Medo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Hipotermia/complicações , Hipóxia/complicações , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Sensação/efeitos dos fármacos , Tiazóis/química , Fatores de Tempo , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/metabolismo , Nervo Vago/efeitos dos fármacos
7.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670768

RESUMO

Lower levels of calcium in adults increase the risk for osteoporosis, and in children, low calcium levels can impact their potential adult height. The study objective was to analyze the bioavailability and physicochemical properties of a calcium preparation based on chicken eggs. The base calcium preparation was enriched with one of a variety of biologically active substances, inter alia, vitamin D3, vitamin K, lysine, lactose, magnesium chloride and inulin. The newly developed calcium preparations were subjected to structural analysis using X-ray diffraction and scanning electron microscopy, and the hydrodynamic diameter for the molecules was determined using the dynamic light scattering method and their zeta potential. To determine the optimum storage conditions of calcium preparations, their hygroscopicity and bulk density were determined. The calcium preparations were also added to selected food products, such as apple juice with mango, fruit dessert (jelly) and beef meatballs. The enriched food products were subjected to sensory analysis. The study demonstrated the significant influence of additives to calcium preparation in terms of its hygroscopicity and morphology. It was found that all products with the addition of analyzed preparations were characterized by high sensory desirability. The results presented in the study comprise the basis for the development of new food products, enriched with calcium.


Assuntos
Cloreto de Cálcio/farmacologia , Casca de Ovo/microbiologia , Modelos Biológicos , Sensação , Animais , Casca de Ovo/efeitos dos fármacos , Hidrodinâmica , Tamanho da Partícula , Sensação/efeitos dos fármacos , Eletricidade Estática , Difração de Raios X
8.
Br J Nutr ; 125(1): 92-100, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-32660667

RESUMO

Stimulation of gastrointestinal taste receptors affects eating behaviour. Intraduodenal infusion of tastants leads to increased satiation and reduced food intake, whereas intraileal infusion of tastants does not affect eating behaviour. Currently, it is unknown whether oral- or intragastric administration of tastants induces a larger effect on eating behaviour. This study investigated the effects of oral- and/or intragastric administration of quinine on food intake, appetite sensations and heart rate variability (HRV). In a blinded randomised crossover trial, thirty-two healthy volunteers participated in four interventions with a 1-week washout: oral placebo and intragastric placebo (OPGP), oral quinine and intragastric placebo (OQGP), oral placebo and intragastric quinine (OPGQ) and oral quinine and intragastric quinine (OQGQ). On test days, 150 min after a standardised breakfast, subjects ingested a capsule containing quinine or placebo and were sham-fed a mixture of quinine or placebo orally. At 50 min after intervention, subjects received an ad libitum meal to measure food intake. Visual analogue scales for appetite sensations were collected, and HRV measurements were performed at regular intervals. Oral and/or intragastric delivery of the bitter tastant quinine did not affect food intake (OPGP: 3273·6 (sem 131·8) kJ, OQGP: 3072·7 (sem 132·2) kJ, OPGQ: 3289·0 (sem 132·6) kJ and OQGQ: 3204·1 (sem 133·1) kJ, P = 0·069). Desire to eat and hunger decreased after OQGP and OPGQ compared with OPGP (P < 0·001 and P < 0·05, respectively), whereas satiation, fullness and HRV did not differ between interventions. In conclusion, sole oral sham feeding with and sole intragastric delivery of quinine decreased desire to eat and hunger, without affecting food intake, satiation, fullness or HRV.


Assuntos
Apetite/efeitos dos fármacos , Agentes Aversivos/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Quinina/administração & dosagem , Sensação/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Idoso , Desjejum , Estudos Cross-Over , Duodeno , Comportamento Alimentar/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Fome/efeitos dos fármacos , Íleo , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Saciação/efeitos dos fármacos , Método Simples-Cego , Adulto Jovem
9.
PLoS Biol ; 18(10): e3000834, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001971

RESUMO

Transcranial alternating current stimulation (tACS) modulates brain activity by passing electrical current through electrodes that are attached to the scalp. Because it is safe and noninvasive, tACS holds great promise as a tool for basic research and clinical treatment. However, little is known about how tACS ultimately influences neural activity. One hypothesis is that tACS affects neural responses directly, by producing electrical fields that interact with the brain's endogenous electrical activity. By controlling the shape and location of these electric fields, one could target brain regions associated with particular behaviors or symptoms. However, an alternative hypothesis is that tACS affects neural activity indirectly, via peripheral sensory afferents. In particular, it has often been hypothesized that tACS acts on sensory fibers in the skin, which in turn provide rhythmic input to central neurons. In this case, there would be little possibility of targeted brain stimulation, as the regions modulated by tACS would depend entirely on the somatosensory pathways originating in the skin around the stimulating electrodes. Here, we directly test these competing hypotheses by recording single-unit activity in the hippocampus and visual cortex of alert monkeys receiving tACS. We find that tACS entrains neuronal activity in both regions, so that cells fire synchronously with the stimulation. Blocking somatosensory input with a topical anesthetic does not significantly alter these neural entrainment effects. These data are therefore consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACS to entrain neurons.


Assuntos
Córtex Somatossensorial/fisiologia , Estimulação Transcraniana por Corrente Contínua , Anestesia , Animais , Combinação Lidocaína e Prilocaína/farmacologia , Macaca mulatta , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Sensação/efeitos dos fármacos , Sensação/fisiologia , Córtex Somatossensorial/efeitos dos fármacos
10.
Eur J Pharmacol ; 887: 173565, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946869

RESUMO

An impaired gut barrier, possibly leading to visceral hypersensitivity has been recently recognized to be one of the pivotal pathophysiology of irritable bowel syndrome (IBS). We previously showed that lipopolysaccharide (LPS), corticotropin-releasing factor (CRF), and repeated water avoidance stress (WAS) induce visceral hypersensitivity and colonic hyperpermeability via pro-inflammatory cytokine signaling (rat IBS models). Although the precise mechanisms of action are unclear, imipramine, a tricyclic antidepressant, improves IBS symptoms, and also has anticytokine properties. In this study, we hypothesized that imipramine improves the gut barrier to ameliorate IBS symptoms. To test this hypothesis, we determined its effects on visceral hypersensitivity and colonic hyperpermeability in rat IBS models. The visceral pain threshold in response to colonic balloon distention was electrophysiologically estimated by abdominal muscle contractions, and colonic permeability was measured by quantifying the absorbed Evans blue in colonic tissue in vivo. Subcutaneous imipramine injection (7, 20, 50 mg/kg) dose-dependently inhibited LPS-induced (1 mg/kg, subcutaneously) visceral hypersensitivity and colonic hyperpermeability. Imipramine also blocked these gastrointestinal (GI) changes induced by CRF (50 µg/kg, intraperitoneally) or repeated WAS (1 h daily for 3 days). Yohimbine (an α2-adrenoceptors antagonist), sulpiride (a dopamine D2 receptor antagonist), and naloxone hydrochloride (an opioid receptor antagonist) reversed these effects of imipramine in the LPS model. Therefore, imipramine may block GI changes in IBS via α2-adrenoceptors, dopamine D2, and opioid signaling. The improvement in the gut barrier resulting in inhibition of visceral pain is considered a valid mechanism of imipramine to ameliorate IBS symptoms.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Imipramina/uso terapêutico , Intestinos/efeitos dos fármacos , Síndrome do Intestino Irritável/tratamento farmacológico , Sensação/efeitos dos fármacos , Músculos Abdominais/efeitos dos fármacos , Animais , Colo/efeitos dos fármacos , Hormônio Liberador da Corticotropina/farmacologia , Relação Dose-Resposta a Droga , Imipramina/antagonistas & inibidores , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/psicologia , Lipopolissacarídeos , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Dor Visceral/tratamento farmacológico , Dor Visceral/etiologia
11.
J Nutr Sci Vitaminol (Tokyo) ; 66(3): 255-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612088

RESUMO

Certain individuals tend to suffer from a cold sensation-particularly in the lower extremities-despite most people not suffering from the same sensation. In Japan, this phenomenon is called "hie-sho" and reduces quality of life for several people, particularly women. A previous study has shown that a standardized oligomerized-polyphenol from Litchi chinensis fruit extract (OPLFE) reportedly causes a significant increase in body surface temperature. The present study aimed to investigate whether supplementation with OPLFE affected peripheral circulation and cold sensitivity. This randomized, double-blind, placebo-controlled trial was performed including 25 participants (age, 45.0±10.4 y; 3 males and 22 females) who were assigned to consume OPLFE, mixed plant extract with OPLFE, or placebo capsules for 14 d. Participants were instructed to relax for 60 min in a temperature-controlled room prior to obtaining measurements. Changes in skin temperature and peripheral blood flow of the middle finger were assessed immediately before and 1, 5, 10, 20, and 30 min after immersion in cold water (10ºC). Participants' height, weight, skin temperature, and blood flow in peripheral tissue were measured; furthermore, their "hie-sho" was measured using the Visual Analog Scale (VAS). Skin temperature and blood flow in peripheral tissue increased in the OPLFE and mixed plant extract with OPLFE groups on day 14 compared with those on day 1. In addition, cold sensitivity in these two groups significantly improved between day 1 and day 14. These findings suggest that OPLFE improves "hie-sho" by increasing peripheral blood flow and skin temperature.


Assuntos
Temperatura Baixa , Litchi/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sensação/efeitos dos fármacos , Temperatura Cutânea/efeitos dos fármacos , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Frutas/química , Humanos , Imersão , Japão , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/normas , Qualidade de Vida , Água
12.
Eur J Nutr ; 59(6): 2317-2332, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32648023

RESUMO

PURPOSE: This systematic review aimed to synthesize the available evidence on the effects of a high-protein diet on appetite sensations in individuals with overweight and obesity. METHODS: Two authors independently conducted literature searches, study selection, design of the method, and quality appraisal. The main inclusion criteria were studies involving protocols that present a protein intake greater than 1.2 g/kg/day or 25% of the total daily energy content compared to a normal protein diet, i.e., 0.8-1.2 g/kg/day or 15%-20% of the total energy content. Studies that evaluated test meals or diet within a period of less than 7 days and participants with diabetes, cancer, or other specific conditions were excluded from this review. The literature search was updated until November 2019 using the main databases available. RESULTS: Of a total of 4191 records, ten articles met the inclusion criteria and included a total of 1079 subjects. In six studies, participants experienced enhanced fullness or satiety in response to a high-dietary protein intake, of which four studies had an intervention period of 10-12 weeks. CONCLUSION: Our results suggest that among individuals with overweight or obesity, higher dietary protein intake may influence appetite sensations by enhancing fullness or satiety. The low level of evidence, due to the heterogeneity of the protocols and the high risk of bias, highlights the need for further studies to confirm these results.


Assuntos
Apetite/efeitos dos fármacos , Apetite/fisiologia , Proteínas na Dieta/farmacologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Humanos , Sensação/efeitos dos fármacos
13.
Mol Pain ; 16: 1744806920926426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418467

RESUMO

Allergic contact dermatitis is a skin inflammatory disease manifested with itch and pain symptom around the inflamed area. Chemokines such as CXCL12 are involved in the pathophysiology of allergic contact dermatitis, but little has been known about the effect of CXCL12/CXCR4 signaling for nociceptive sensation accompanying allergic contact dermatitis. Our study showed that CXCL12 and CXCR4 were upregulated in trigeminal ganglion with the progression of allergic contact dermatitis through western blotting and immunofluorescence. CXCL12 and CXCR4 were mainly upregulated in small-diameter neurons, which were co-localized with nociceptive markers in trigeminal ganglion. CXCR4 and CXCL12 were also expressed in trigeminal ganglion neurons retrograded from the skin lesion. Intradermal injection of CXCL12 enhanced the itch- and pain-like behavior which could be relieved by AMD3100, a CXCR4 antagonist, without changes of mast cells. Our findings suggested that blockade of CXCL12/CXCR4 signaling pathway might be beneficial to relieve itch and pain sensation accompanying allergic contact dermatitis.


Assuntos
Quimiocina CXCL12/metabolismo , Dermatite Alérgica de Contato/complicações , Dor/complicações , Prurido/complicações , Receptores CXCR4/metabolismo , Sensação , Transdução de Sinais , Animais , Comportamento Animal/efeitos dos fármacos , Benzilaminas/farmacologia , Degranulação Celular/efeitos dos fármacos , Ciclamos/farmacologia , Dermatite Alérgica de Contato/patologia , Modelos Animais de Doenças , Inflamação/patologia , Ligantes , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nociceptividade/efeitos dos fármacos , Dor/patologia , Prurido/patologia , Sensação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Pele/inervação , Pele/patologia , Regulação para Cima/efeitos dos fármacos
15.
Neuroreport ; 31(12): 865-870, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32453026

RESUMO

Nociceptors arising from the dorsal root ganglia (DRG) express acid-sensing ion channel-1 (ASIC1) subtypes to mediate the perception of inflammatory and neuropathic pain, and as such, these receptors are attractive targets for the development of analgesics for these painful conditions. Nevertheless, given that the human and rodent DRG differ considerably in subtype proportions of ASIC1 and that the pharmacological properties of rodent ASIC1 subtypes and their human homologues are distinct, ASIC1 inhibitors that demonstrate analgesic properties in rodents may not necessarily be effective in preventing pain in humans. In this study, we show that human embryonic kidney (HEK) 293 cells, which are routinely used as a cellular vehicle for the heterologous expression and pharmacological characterization of receptors and ion channels, natively transcribe the human homologues of ASIC1a and ASIC1b at similar proportions to those found in the human DRG. Importantly, HEK 293 ASIC1 is sensitive to inhibition by amiloride, ethylisopropyl amiloride, and the snake toxin mambalgin-1, but insensitive to inhibition by the ASIC1a inhibitor psalmotoxin-1 when applied at a physiological conditioning pH. Given that the human DRG transcribes the same set of ASIC1 subtypes as HEK 293 cells, our data support the notion that mambalgin-1 may be effective against acid pain sensation in humans. Moreover, our data suggest that the HEK 293 cell line may be a suitable tool for pharmacological screening and characterization of heteromeric human ASIC1.


Assuntos
Canais Iônicos Sensíveis a Ácido/efeitos dos fármacos , Analgésicos/farmacologia , Neuralgia/tratamento farmacológico , Sensação/efeitos dos fármacos , Canais Iônicos Sensíveis a Ácido/metabolismo , Animais , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Células HEK293 , Humanos , Neuralgia/metabolismo , Xenopus laevis/metabolismo
16.
Nutrients ; 12(5)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32353974

RESUMO

Suppression of oral sweet sensation (OSS) acutely reduces intake of sweet-tasting food due to lower liking. However, little is known about other physiological responses during both the prandial and postprandial phase. Here, we explored the effects of Gymnema sylvestre (GS)-based suppression of OSS of several types of sweet-tasting food (muffin, sweet yogurt, banana) on gastric emptying, blood glucose (BG), plasma insulin (PI), appetite indices (hunger, fullness and prospective consumption), satisfaction and desire for tastes. Fifteen healthy subjects (22 ± 3 years, 9 women) took part in the study. Subjects rinsed their mouth with either GS solution or distilled water before eating the sweet-tasting food. Subjects felt decreased sweet taste intensity and reduced taste liking associated with GS rinsing after consuming each food, compared with rinsing with distilled water (p < 0.05). Gastric emptying, BG, PI and appetite indices during and after the prandial phase did not significantly change with GS rinsing compared to rinsing with distilled water (p > 0.05). Higher desire for sweet taste as well as lower satisfaction (p < 0.05) in the postprandial phase were observed with GS rinsing. These results suggest that the suppression of OSS does not affect gastric emptying, glycemic response and appetite during and after consumption of sweet-tasting food.


Assuntos
Apetite/efeitos dos fármacos , Glicemia , Ingestão de Alimentos/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Esvaziamento Gástrico/efeitos dos fármacos , Gymnema sylvestre/química , Satisfação Pessoal , Extratos Vegetais/farmacologia , Período Pós-Prandial/fisiologia , Sensação/efeitos dos fármacos , Edulcorantes , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Adulto , Apetite/fisiologia , Estudos Cross-Over , Ingestão de Alimentos/fisiologia , Feminino , Preferências Alimentares/fisiologia , Esvaziamento Gástrico/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Sensação/fisiologia , Paladar/fisiologia , Percepção Gustatória/fisiologia , Adulto Jovem
17.
Neuropharmacology ; 171: 108110, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32344007

RESUMO

MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01-15 mg/kg i.p.) on motor and sensorimotor (visual, acoustic and tactile) responses, mechanical and thermal analgesia, muscle strength and body temperature in CD-1 male mice. Higher doses of MT-45 (6-30 mg/kg i.p.) were used to investigate cardiorespiratory changes (heart rate, respiratory rate, SpO2 saturation and pulse distention). All effects of MT-45 were compared with those of morphine. In vitro DMR assay results demonstrated that at human recombinant opioid receptors MT-45 behaves as a potent selective mu agonist with a slightly higher efficacy than morphine. In vivo results showed that MT-45 progressively induces tail elevation at the lowest dose tested (0.01 mg/kg), increased mechanical and thermal antinociception (starting from 1 to 6 mg/kg), decreased visual sensorimotor responses (starting from 3 to 6 mg/kg) and reduced tactile responses, modulated motor performance and induced muscle rigidity at higher doses (15 mg/kg). In addition, at higher doses (15-30 mg/kg) MT-45 impaired the cardiorespiratory functions. All effects were prevented by the administration of the opioid receptor antagonist naloxone. These findings reveal the risks associated with the ingestion of opioids and the importance of studying these drugs and undertaking more clinical studies of the current molecules to better understand possible therapeutic interventions in the case of toxicity.


Assuntos
Analgésicos Opioides/farmacologia , Piperazinas/farmacologia , Agressão/efeitos dos fármacos , Analgésicos Opioides/antagonistas & inibidores , Animais , Células CHO , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Hemodinâmica/efeitos dos fármacos , Temperatura Alta , Humanos , Camundongos , Morfina/antagonistas & inibidores , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/efeitos dos fármacos , Estimulação Física , Piperazinas/antagonistas & inibidores , Receptores Opioides/efeitos dos fármacos , Respiração/efeitos dos fármacos , Sensação/efeitos dos fármacos
18.
Pak J Pharm Sci ; 33(1): 183-189, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122847

RESUMO

The current study focused on the development, optimization and pharmaceutical evaluation of a mouth dissolving film of Escitalopram 5mg. The designing and optimization of the formulations have been carried out through Design-Expert ⌖ Ver. 9, using central composite response surface methodology. The software generated six optimized formulations have been fabricated via solvent casting method incorporated with HPMC and PEG 400 as Plasticizer. The developed formulations were assessed for various quality attributes including weight variation, drug-excipients interaction, dryness/ tack test, thickness, percent elongation, swelling index, disintegration, folding endurance, surface pH, content uniformity, assay, moisture uptake, stability, and organoleptic properties. A validated spectrophotometric method has been used to ascertain drug content. The formulations were subjected for stability studies for six months in accordance with ICH accelerated stability studies guidelines. No stability issue has been observed. All the test formulations have shown satisfactory in vitro release of escitalopram whereas most promising results have been exhibited by F5 and F6 formulations. The study concluded that a unique, novel, safe and stable formulation of oral fast dissolving thin films of escitalopram can be formulated with ease. The preparation method was simple and reproducible with scale-up tendency so that it can fulfill the need of the commercial manufacturing process.


Assuntos
Citalopram/química , Citalopram/farmacologia , Composição de Medicamentos/métodos , Administração Oral , Citalopram/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Derivados da Hipromelose/química , Fenômenos Físicos , Polietilenoglicóis/química , Sensação/efeitos dos fármacos , Solubilidade , Espectrofotometria/métodos , Propriedades de Superfície
19.
Pak J Pharm Sci ; 33(1): 191-197, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122848

RESUMO

Whey plays an important role in the sports nutrition because of high quality proteins and essential amino acid profile. Nine formulations of sportsman drinks were made using Cheddar, Mozzarella and Paneer whey with normal as well as additional fermentation. The developed sportsman drinks were evaluated for physico-chemical analyses, amino acid profile, viscosity and total plate count along with sensory response during two month storage. Drink having Cheddar whey (T4) with additional fermentation was better in terms of quality and nutrition. Furthermore, amino acid profile considered it a complete and balanced source of essential and non-essential amino acids. Amongst essential amino acids, highest values was recorded for branched chain amino acids like leucine (73.16±3.09) followed by lysine (61.56±0.61) and valine (44.13±1.86)mg/g protein. The dietary significance of sportsman drink can be enhanced through additional fermentation using Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophillus.


Assuntos
Bebidas , Composição de Medicamentos/métodos , Probióticos/química , Esportes , Proteínas do Soro do Leite/química , Aminoácidos/análise , Fenômenos Químicos , Armazenamento de Medicamentos , Fermentação , Humanos , Lactobacillus delbrueckii/química , Sensação/efeitos dos fármacos , Streptococcus thermophilus/química
20.
Dev Psychobiol ; 62(5): 559-572, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32115695

RESUMO

Each year, millions of children undergo anesthesia, and both human and animal studies have indicated that exposure to anesthesia at an early age can lead to neuronal damage and learning deficiency. However, disorders of sensory functions were not reported in children or animals exposed to anesthesia during infancy, which is surprising, given the significant amount of damage to brain tissue reported in many animal studies. In this review, we discuss the relationship between the systems in the brain that mediate sensory input, spatial learning, and classical conditioning, and how these systems could be affected during anesthesia exposure. Based on previous reports, we conclude that anesthesia can induce structural, functional, and compensatory changes in both sensory and learning systems. Changes in myelination following anesthesia exposure were observed as well as the neurodegeneration in the gray matter across variety of brain regions. Disproportionate cell death between excitatory and inhibitory cells induced by anesthesia exposure can lead to a long-term shift in the excitatory/inhibitory balance, which affects both learning-specific networks and sensory systems. Anesthesia may directly affect synaptic plasticity which is especially critical to learning acquisition. However, sensory systems appear to have better ability to compensate for damage than learning-specific networks.


Assuntos
Anestesia/efeitos adversos , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/induzido quimicamente , Aprendizagem/efeitos dos fármacos , Sensação/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Criança , Humanos , Lactente , Macaca mulatta , Camundongos , Plasticidade Neuronal/efeitos dos fármacos , Ratos
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