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1.
Microb Pathog ; 189: 106607, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437995

RESUMO

OBJECTIVES: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. METHODS: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 µM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. RESULTS: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. CONCLUSION: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.


Assuntos
Anti-Infecciosos , Endorfinas , Mariposas , Animais , Proteômica , Mariposas/microbiologia , Antibacterianos/farmacologia , Larva , Peptídeos
2.
J Therm Biol ; 118: 103727, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866096

RESUMO

Cold water immersion (CWI) may provide benefits for physical and mental health. Our purpose was to investigate the effects of an acute bout of CWI on vascular shear stress and affect (positive and negative). Sixteen healthy adults (age: 23 ± 4 y; (9 self-reported men and 7 self-reported women) completed one 15-min bout of CWI (10 °C). Self-reported affect (positive and negative) was assessed at pre-CWI (Pre), 30-min post-immersion, and 180-min post-immersion in all participants. Brachial artery diameter and blood velocity were measured (Doppler ultrasound) at Pre, after 1-min and 15-min of CWI, and 30-min post-immersion (n = 8). Total, antegrade, and retrograde shear stress, oscillatory shear index (OSI), and forearm vascular conductance (FVC) were calculated. Venous blood samples were collected at Pre, after 1-min and 15-min of CWI, 30-min post-immersion, and 180-min post-immersion (n = 8) to quantify serum ß-endorphins and cortisol. Data were analyzed using a one-way ANOVA with Fisher's least significance difference and compared to Pre. Positive affect did not change (ANOVA p = 0.450) but negative affect was lower at 180-min post-immersion (p < 0.001). FVC was reduced at 15-min of CWI and 30-min post-immersion (p < 0.020). Total and antegrade shear and OSI were reduced at 30-min post-immersion (p < 0.040) but there were no differences in retrograde shear (ANOVA p = 0.134). ß-endorphins did not change throughout the trial (ANOVA p = 0.321). Cortisol was lower at 180-min post-immersion (p = 0.014). An acute bout of CWI minimally affects shear stress patterns but may benefit mental health by reducing negative feelings and cortisol levels.


Assuntos
Temperatura Baixa , Endorfinas , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Afeto , Hidrocortisona , Imersão , Água
3.
Int J Sports Physiol Perform ; 18(12): 1420-1426, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37734742

RESUMO

PURPOSE: Advanced footwear technology is prevalent in distance running, with research focusing on these "super shoes" in competitive athletes, with less understanding of their value for slower runners. The aim of this study was to compare physiological and biomechanical variables between a model of super shoes (Saucony Endorphin Speed 2) and regular running shoes (Saucony Cohesion 13) in recreational athletes. METHODS: We measured peak oxygen uptake (VO2peak) in 10 runners before testing each subject 4 times in a randomly ordered crossover design (ie, Endorphin shoe or Cohesion shoe, running at 65% or 80% of velocity at VO2peak [vVO2peak]). We recorded video data using a high-speed camera (300 Hz) to calculate vertical and leg stiffnesses. RESULTS: 65% vVO2peak was equivalent to a speed of 9.4 km·h-1 (0.4), whereas 80% vVO2peak was equivalent to 11.5 km·h-1 (0.5). Two-way mixed-design analysis of variance showed that oxygen consumption in the Endorphin shoe was 3.9% lower than in the Cohesion shoe at 65% vVO2peak, with an interaction between shoes and speed (P = .020) meaning an increased difference of 5.0% at 80% vVO2peak. There were small increases in vertical and leg stiffnesses in the Endorphin shoes (P < .001); the Endorphin shoe condition also showed trivial to moderate differences in step length, step rate, contact time, and flight time (P < .001). CONCLUSIONS: There was a physiological benefit to running in the super shoes even at the slower speed. There were also spatiotemporal and global stiffness improvements indicating that recreational runners benefit from wearing super shoes.


Assuntos
Endorfinas , Corrida , Humanos , Fenômenos Biomecânicos , Corrida de Maratona , Corrida/fisiologia , Sapatos , Estudos Cross-Over
4.
Gastroenterol. hepatol. (Ed. impr.) ; 46(6): 419-424, Jun-Jul. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-220846

RESUMO

Objective: It has been reported that professional cyclists had an accelerated solid gastric emptying which decreased by increasing the exercise intensity. That could be explained by a predominance of stress-dependent motility inhibitors such gastrointestinal hormones, neurotransmitters and or the predominance of the gastric inhibitory vagal motor circuit. The aim of this preliminary study was to evaluate the role of β-endorphins, inhibitors of gastric motility, in these findings. Methods: Gastric emptying of solids marked with Tc99 while resting and plasmatic levels of β-endorphins were evaluated in 27 healthy controls and 19 professional cyclists (day 1). Besides, gastric emptying of solids was also assessed in cyclists when they reached 50% (day 1) and 75% (day 2) of the maximum oxygen consumption (low and high, respectively), during exercise on the cycle-ergometer. The third day, naloxone was administered in cyclists in order to block the β-endorphins receptors and gastric emptying was measured when they reached 75% of the maximum oxygen consumption. Results: Basal β-endorphin levels were lower in cyclists vs controls (p<0.05) and they increased with the exercise intensity (p<0.001). There were no significant differences in gastric emptying of solids with or without naloxone when 75% of the maximum oxygen consumption was reached. Conclusions: The inhibitory effect of the exercise in the gastric emptying of solids does not seem to be secondary to the action of β-endorphins, that leaves the gastric inhibitory vagal motor circuit a more likely predominant role.(AU)


Objetivo: Se ha informado de que los ciclistas profesionales tienen un vaciado gástrico sólido acelerado que disminuye al aumentar la intensidad del ejercicio. Esto podría explicarse por un predominio de los inhibidores de la motilidad dependientes del estrés, como las hormonas gastrointestinales, los neurotransmisores y o el predominio del circuito motor vagal inhibidor gástrico. El objetivo de este estudio preliminar fue evaluar el papel de las β-endorfinas, inhibidores de la motilidad gástrica, en estos hallazgos. Métodos: Se evaluó el vaciado gástrico de sólidos marcado con Tc99 mientras se evaluaban los niveles en reposo y plasmáticos de β-endorfinas en 27 controles sanos y 19 ciclistas profesionales (día 1). Además, también se evaluó el vaciado gástrico de sólidos en los ciclistas cuando alcanzaron el 50% (día 1) y el 75% (día 2) del consumo máximo de oxígeno (bajo y alto, respectivamente), durante el ejercicio en el cicloergómetro. El tercer día, se administró naloxona en los ciclistas para bloquear los receptores de β-endorfinas y se midió el vaciado gástrico cuando alcanzaron el 75% del consumo máximo de oxígeno. Resultados: Los niveles basales de β-endorfina fueron menores en los ciclistas frente a los controles (p<0,05) y aumentaron con la intensidad del ejercicio (p<0,001). No hubo diferencias significativas en el vaciado gástrico de sólidos con o sin naloxona cuando se alcanzó el 75% del consumo máximo de oxígeno. Conclusiones: El efecto inhibidor del ejercicio en el vaciado gástrico de sólidos no parece ser secundario a la acción de las β-endorfinas, lo que deja al circuito motor vagal inhibitorio gástrico un papel más probablemente predominante.(AU)


Assuntos
Humanos , Endorfinas , Esvaziamento Gástrico , Atletas , Ciclismo
5.
Med Arch ; 77(2): 127-131, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37260806

RESUMO

Background: Endorphin is a biological change in molecular physiology that is commonly connected with anxiety. An increase in the level of anxiety is caused by both an increase and a decrease in the number of endorphins that are present in the brain; however, up until this point, it has never been reported that there is a relationship between the level of anxiety and the influence of interval training. Objective: The purpose of this study was to analyze the effect of training interval on endorphin level and anxiety degrees of secaba student soldiers with moderate degrees of anxiety. Methods: The subject of the study was a student soldier of Secaba Rindam III Siliwangi with moderate anxiety. The subject of the study gets information about the objectives and procedures of the study. Subjects who are willing to participate in the study sign informed consent. The next step was that group 1 was given an interval training treatment 3 times a week for 12 weeks and group 2 was given continuous training treatment. Results: The results showed that there was a difference where interval training is better than continuous training against increasing endorphin levels (30.9111.733 vs. 39.6519.956; p=0.043). The degree of anxiety decreased significantly after being given interval training treatment (64.64±3.671 vs. 29.50±4.165; p=0.0001). Similarly, there was a significant difference (p=0.027; p<0.05) where the treatment in the interval training group was better than that of the continuous training group against a decrease in the degree of anxiety. Conclusion: Interval training can increase endorphin levels in Secaba Rindam III Siliwangi Student Soldiers with Moderate Anxiety and Interval Training can lower the Degree of Anxiety in Secaba Rindam III Siliwangi Student Soldiers with Moderate Anxiety.


Assuntos
Endorfinas , Militares , Humanos , beta-Endorfina , Ansiedade/terapia , Estudantes
6.
J Phys Chem B ; 127(5): 1089-1096, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36696655

RESUMO

As a functional amyloid, human ß-endorphin amyloid fibril features a ß-solenoid conformation and store peptide hormones within acidic secretory granules, which would be released into the blood through fibril disassembly when the cellular milieu pH increases from acidic to neutral level on exocytosis. To gain detailed atomic mechanism of ß-endorphin amyloid fibrils' pH-responsive disassembly, we conduct constant pH molecular dynamics simulations to investigate the structural and dynamical properties of ß-endorphin amyloid fibrils in experiencing the environmental pH changes. Our results demonstrate a clear pKa shift of the internal ionizable residue of GLU8, and this shift becomes even more pronounced when it is buried more deeply in the amyloid fibrils. The unusual pKa of GLU8 reveals that its protonation state changes from the protonated state in the acidic secretory granule to the deprotonated state in the neutral pH conditions in the blood, where the deprotonation of GLU8 leads to unfavorable interactions within the hydrophobic core of the amyloid and subsequent fibril disassembly. The different pKa shifts of GLU8 relative to its positions in the amyloid fibril indicate that the ß-endorphin amyloid fibril disassembly is a stepwise process, accounting for the experimental observation that the disassembly always initiates from the outermost layer. This study reveals the critical role of the protonation state of GLU8 in amyloid fibrils' pH-responsive disassembly, and provides clear insights for understanding the structural transitions of amyloids in hormone secretion. This study also provides theoretical basis for designing pH-sensitive biological tools for specific use with precise positioning of ionizable residues into the hydrophobic interior of proteins.


Assuntos
Amiloide , Endorfinas , Humanos , Amiloide/química , beta-Endorfina/química , Peptídeos beta-Amiloides , Simulação de Dinâmica Molecular , Concentração de Íons de Hidrogênio
7.
Anesth Analg ; 135(5): 1120-1121, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36269988

Assuntos
Endorfinas , Radiografia
8.
PLoS One ; 17(10): e0274331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36197910

RESUMO

BACKGROUND & OBJECTIVES: Pain can be significantly lessened by sex/orgasm, likely due to the release of endorphins during sex, considered potent analgesics. The evidence suggests that endorphins are also present during sexual arousal (that is, prior to sex/orgasm). It follows then that pain can be modulated during sexual arousal, independent of sex/orgasm, too. Accordingly, sexual arousal induced by erotic slides has been demonstrated to lessen pain in men, but not in women. One explanation could be that for women, the erotic slides were not potent enough to elicit a lasting primed state of sexual arousal by the time pain was induced. Thus, the current study aims to optimize the means of inducing a potent state of sexual arousal and subsequently examine the potentially analgesic influence of sexual arousal on pain in women. As a subsidiary aim, the study also assesses whether the anticipated analgesic effect of sexual arousal would be stronger than that of distraction or generalized (non-sexual) arousal. METHODS: Female participants (N = 151) were randomly distributed across four conditions: sexual arousal, generalized arousal, distraction, neutral. Mild pain was induced using a cold pressor while participants were concurrently exposed to film stimuli (pornographic, exciting, distracting, neutral) to induce the targeted emotional states. A visual analogue scale was utilized to measure the subjective level of pain perceived by the participants. RESULTS: Sexual arousal did not reduce subjective pain. Generalized arousal and distraction did not result in stronger analgesic effects than the neutral condition. CONCLUSION: The present findings do not support the hypothesis that sexual arousal alone modulates subjective pain in women. This might be due to the possibility that genital stimulation and/or orgasm are key in pain reduction, or, that feelings of disgust may inadvertently have been induced by the pornographic stimulus and interfered with sexual arousal in influencing pain.


Assuntos
Endorfinas , Excitação Sexual , Literatura Erótica , Feminino , Humanos , Masculino , Orgasmo/fisiologia , Dor , Medição da Dor , Comportamento Sexual/psicologia
9.
Philos Trans R Soc Lond B Biol Sci ; 377(1863): 20210176, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36126664

RESUMO

In anthropoid primates, social grooming is the principal mechanism (mediated by the central nervous system endorphin system) that underpins social bonding. However, the time available for social grooming is limited, and this imposes an upper limit on the size of group that can be bonded in this way. I suggest that, when hominins needed to increase the size of their groups beyond the limit that could be bonded by grooming, they co-opted laughter (a modified version of the play vocalization found widely among the catarrhine primates) as a form of chorusing to fill the gap. I show, first, that human laughter both upregulates the brain's endorphin system and increases the sense of bonding between those who laugh together. I then use a reverse engineering approach to model group sizes and grooming time requirements for fossil hominin species to search for pinch points where a phase shift in bonding mechanisms might have occurred. The results suggest that the most likely time for the origin of human-like laughter is the appearance of the genus Homo ca 2.5 Ma. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.


Assuntos
Endorfinas , Hominidae , Riso , Animais , Asseio Animal/fisiologia , Humanos , Riso/fisiologia , Primatas
10.
Trials ; 23(1): 740, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064731

RESUMO

BACKGROUND: Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient's adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life. METHODS: This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage. DISCUSSION: The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058092.


Assuntos
Endorfinas , Fibromialgia , Fibromialgia/diagnóstico , Fibromialgia/terapia , Humanos , Estudos Multicêntricos como Assunto , Dor , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Artigo em Inglês | MEDLINE | ID: mdl-36078233

RESUMO

The aim of this study was to evaluate the influence of ß-endorphins and serotonin on the course of treatment, disease-free time, and overall survival of patients with ovarian cancer. This study may contribute to the identification of modifiable factors that may influence the treatment of ovarian cancer. The research was carried out in a group of 162 patients of which 139 respondents were included in the research; ovarian cancer was diagnosed in 78 of these patients. The study consisted of three stages. In the first stage of diagnostics, a survey among the patients was carried out. In the second stage-5 mL of blood was collected from each patient (n = 139) in the preoperative period to determine the concentration of ß-endorphin and serotonin. In the third stage-blood samples were collected from those patients who had completed chemotherapy treatment or had surgery. Concentrations of ß-endorphin and serotonin were measured by the Luminex method, using the commercial Luminex Human Discovery Assay kit. The average age of the patients was 62.99 years. The level of ß-endorphin significantly differs among patients diagnosed with ovarian cancer and among patients in the control group (202.86; SD-15.78 vs. 302.00; SD-24.49). A lower level of ß-endorphins was found in the patients with a recurrence of the neoplastic process compared to those without recurrence (178.84; SD-12.98 vs. 205.66; SD-13.37). On the other hand, the level of serotonin before chemotherapy was higher in the group of people with disease recurrence compared to those without recurrence (141.53; SD-15.33 vs. 134.99; SD-10.08). Statistically significantly positive correlations were found between the level of ß-endorphin and both disease-free time (ß-endorphin levels before chemotherapy: rho Spearman 0.379, p < 0.027; ß-endorphin levels after chemotherapy: rho Spearman 0.734 p < 0.001) and survival time (ß-endorphin levels before chemotherapy: rho Spearman 0.267, p < 0.018; ß-endorphin levels after chemotherapy: rho Spearman 0.654 p < 0.001). 1. The levels of serotonin and ß-endorphin levels are significantly related to ovarian cancer and change during treatment. 2. High mean preoperative concentrations of ß-endorphins were significantly related to overall survival and disease-free time.


Assuntos
Endorfinas , Neoplasias Ovarianas , Serotonina , beta-Endorfina , Fatores Biológicos , Endorfinas/química , Endorfinas/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Serotonina/química , Serotonina/metabolismo , beta-Endorfina/metabolismo
12.
J Dairy Sci ; 105(7): 5545-5560, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35534270

RESUMO

The non-systematic evolution of ligands by the exponential enrichment (non-SELEX) method was used in the present study for the selection of ß-casomorphin-7 (BCM-7)-specific aptamers. These aptamers were tested to evaluate their ability to detect BCM-7 peptide in the human urine sample. The method did not employ aptamer amplification and counterselection as used in conventional SELEX but included a negative round of selection. The selection was performed in a single day, and after 5 rounds, a total of 16 numbers of aptamer were identified through Sanger sequencing. Newly selected aptamers named sequence ID no. 3 have performed better than other aptamers in detecting the BCM-7 peptide. Sequence ID no. 3 was also compared with previously selected aptamers through the SELEX method and its performance was found to be better than old aptamers. The sensing experiment was tried on different platforms from magnetic beads to the membrane. In each strategy, satisfactory results were obtained with aptamers that recognized BCM-7 spiked in a human urine sample at a very low amount. The non-SELEX method is an easy and time-saving process for aptamer selection. Selection of viable aptamers from a large pool of sequences for sensing experiments is a tedious job; however, an attempt has been made to select aptamers on the basis of In Silico (http://www.unafold.org/, https://bioinformatics.ramapo.edu/QGRS/index.php) information, observing DNA band intensity on agarose gel and colorimetric results obtained on magnetic beads and membrane. These aptamers have the potential in biosensor making for detecting BCM-7 peptide in urine samples of autistic patients.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Animais , Aptâmeros de Nucleotídeos/genética , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/veterinária , Endorfinas , Humanos , Ligantes , Técnica de Seleção de Aptâmeros/métodos , Técnica de Seleção de Aptâmeros/veterinária
13.
J Sports Sci Med ; 21(1): 127-130, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35250342

RESUMO

Road-racing shoes recently experienced major changes. In the recent past, lightweight, thin midsole shoes were thought to help runners maximize their performance. But, in 2017, Nike released the Vaporfly shoe which transformed the thinking about racing shoe design. Incorporating a curved carbon fiber plate embedded in a thick, compliant and resilient midsole resulted in a reduced metabolic cost across a range of running speeds. We hypothesized the new style of shoes would be less effective uphill than downhill due to the larger ground reaction forces and hence greater elastic energy storage in the shoe during downhill running. Eighteen runners completed two days of testing, each comprising two trials of two shoe models (Saucony Endorphin Pro (EP) and Type A) and three grade conditions (uphill, level and downhill), i.e. 12 trials per day. Oxygen uptake, ground reaction forces, and lower-body kinematics were captured during each condition. Comparisons of the percent metabolic benefit were made between shoes for each grade. Stride rate, ground time, peak vertical force, and flight time were regressed with the percent metabolic benefit of the EP over the Type A shoe across grades. Metabolic benefits of the Endorphin Pro were similar across the three grade conditions (p = 0.778). No significant correlations were observed between how much benefit one runner got over another specific to grade. The new style of road-racing shoes effectively decreases metabolic cost equally across grades. Differences in running mechanics between runners did not explain greater individual metabolic benefits between shoe conditions during uphill or downhill running.


Assuntos
Endorfinas , Corrida , Fenômenos Biomecânicos , Fibra de Carbono , Humanos , Sapatos
14.
J Sport Health Sci ; 11(3): 275-284, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264686

RESUMO

PURPOSE: We compared running economy (RE) and 3-km time-trial (TT) variables of runners wearing Nike Vaporfly 4% (VP4), Saucony Endorphin lightweight racing flats (FLAT), and their habitual running (OWN) footwear. METHODS: Eighteen male recreational runners (age = 33.5 ± 11.9 year (mean ± SD), peak oxygen uptake (VO2peak) = 55.8 ± 4.4 mL/kg·min) attended 4 sessions approximately 7 days apart. The first session consisted of a VO2peak test to inform subsequent RE speeds set at 60%, 70%, and 80% of the speed eliciting VO2peak. In subsequent sessions, treadmill RE and 3-km TTs were assessed in the 3 footwear conditions in a randomized, counterbalanced crossover design. RESULTS: Oxygen consumption (mL/kg·min) was less in VP4 (from 4.3% to 4.4%, p ≤ 0.002) and FLAT (from 2.7% to 3.4%, p ≤ 0.092) vs. OWN across intensities, with a non-significant difference between VP4 and FLAT (1.0%-1.7%, p ≥ 0.292). Findings related to energy cost (W/kg) and energetics cost of transport (J/kg·m) were comparable. VP4 3-km TT performance (11:07.6 ± 0:56.6 mm:ss) was enhanced vs. OWN by 16.6 s (2.4%, p = 0.005) and vs. FLAT by 13.0 s (1.8%, p = 0.032). The 3-km times between OWN and FLAT (0.5%, p = 0.747) were similar. Most runners (n = 11, 61%) ran their fastest TT in VP4. CONCLUSION: Overall, VP4 improved laboratory-based RE measures in male recreational runners at relative speeds compared to OWN, but the RE improvements in VP4 were not significant vs. FLAT. More runners exhibited better treadmill TT performances in VP4 (61%) vs. FLAT (22%) and OWN (17%). The variability in RE (-10.3% to 13.3%) and TT (-4.7% to 9.3%) improvements suggests that responses to different types of shoes are individualized and warrant further investigation.


Assuntos
Endorfinas , Corrida , Adulto , Fenômenos Biomecânicos , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Corrida/fisiologia , Sapatos , Adulto Jovem
15.
J Med Chem ; 64(22): 16801-16819, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34781680

RESUMO

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.


Assuntos
Analgésicos Opioides/efeitos adversos , Analgésicos/química , Analgésicos/farmacologia , Endorfinas/química , Endorfinas/farmacologia , Peptídeos/química , Animais , Encéfalo/metabolismo , Condicionamento Operante/efeitos dos fármacos , Endorfinas/uso terapêutico , Trânsito Gastrointestinal/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Dor/tratamento farmacológico , Peptídeos/uso terapêutico
16.
Biomolecules ; 11(8)2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34439743

RESUMO

Physical exercise has wide-ranging benefits to cognitive functioning and mental state, effects very closely resembling enhancements to hippocampal functioning. Hippocampal neurogenesis has been implicated in many of these mental benefits of exercise. However, precise mechanisms behind these effects are not well known. Released peripherally during exercise, beta-endorphins are an intriguing candidate for moderating increases in neurogenesis and the related behavioral benefits of exercise. Although historically ignored due to their peripheral release and status as a peptide hormone, this review highlights reasons for further exploring beta-endorphin as a key mediator of hippocampal neurogenesis. This includes possible routes for beta-endorphin signaling into the hippocampus during exercise, direct effects of beta-endorphin on cell proliferation and neurogenesis, and behavioral effects of manipulating endogenous opioid signaling. Together, beta-endorphin appears to be a promising mechanism for understanding the specific ways that exercise promotes adult neurogenesis specifically and brain health broadly.


Assuntos
Endorfinas/metabolismo , Exercício Físico , Hipocampo/metabolismo , Neurogênese , Neurônios/metabolismo , Adulto , Animais , Hipocampo/citologia , Humanos , Camundongos , Neurônios/citologia
17.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360996

RESUMO

ß-Casomorphin-7 (BCM) is a degradation product of ß-casein, a milk component, and has been suggested to affect the immune system. However, its effect on mucosal immunity, especially anti-tumor immunity, in cancer-bearing individuals is not clear. We investigated the effects of BCM on lymphocytes using an in vitro system comprising mouse splenocytes, a mouse colorectal carcinogenesis model, and a mouse orthotopic colorectal cancer model. Treatment of mouse splenocytes with BCM in vitro reduced numbers of cluster of differentiation (CD) 20+ B cells, CD4+ T cells, and regulatory T cells (Tregs), and increased CD8+ T cells. Administration of BCM and the CD10 inhibitor thiorphan (TOP) to mice resulted in similar alterations in the lymphocyte subsets in the spleen and intestinal mucosa. BCM was degraded in a concentration- and time-dependent manner by the neutral endopeptidase CD10, and the formed BCM degradation product did not affect the lymphocyte counts. Furthermore, degradation was completely suppressed by TOP. In the azoxymethane mouse colorectal carcinogenesis model, the incidence of aberrant crypt foci, adenoma, and adenocarcinoma was reduced by co-treatment with BCM and TOP. Furthermore, when CT26 mouse colon cancer cells were inoculated into the cecum of syngeneic BALB/c mice and concurrently treated with BCM and TOP, infiltration of CD8+ T cells was promoted, and tumor growth and liver metastasis were suppressed. These results suggest that by suppressing the BCM degradation system, the anti-tumor effect of BCM is enhanced and it can suppress the development and progression of colorectal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Endorfinas/uso terapêutico , Linfócitos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Células Cultivadas , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Endorfinas/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Linfócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Fragmentos de Peptídeos/farmacologia , Inibidores de Proteases/farmacologia , Baço/citologia , Baço/imunologia , Tiorfano/farmacologia
18.
Sci Adv ; 7(24)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34117054

RESUMO

The current opioid epidemic warrants a better understanding of genetic and environmental factors that contribute to opioid addiction. Here we report an increased prevalence of vitamin D (VitD) deficiency in patients diagnosed with opioid use disorder and an inverse and dose-dependent association of VitD levels with self-reported opioid use. We used multiple pharmacologic approaches and genetic mouse models and found that deficiencies in VitD signaling amplify exogenous opioid responses that are normalized upon restoration of VitD signaling. Similarly, physiologic endogenous opioid analgesia and reward responses triggered by ultraviolet (UV) radiation are repressed by VitD signaling, suggesting that a feedback loop exists whereby VitD deficiency produces increased UV/endorphin-seeking behavior until VitD levels are restored by cutaneous VitD synthesis. This feedback may carry the evolutionary advantage of maximizing VitD synthesis. However, unlike UV exposure, exogenous opioid use is not followed by VitD synthesis (and its opioid suppressive effects), contributing to maladaptive addictive behavior.


Assuntos
Endorfinas , Transtornos Relacionados ao Uso de Opioides , Deficiência de Vitamina D , Analgésicos Opioides/farmacologia , Animais , Humanos , Camundongos , Vitamina D/farmacologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitaminas
19.
Neurotoxicol Teratol ; 86: 107002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34126203

RESUMO

The elevated presence of opioid receptors and their ligands throughout the developing brain points to the existence of maturational functions of the endogenous opioid system that still remain poorly understood. The alarmingly increasing rates of opioid use and abuse underscore the urgent need for clear identification of those functions and the cellular bases and molecular mechanisms underlying their physiological roles under normal and pathological conditions. This review is focused on current knowledge on the direct and indirect regulatory roles that opioids may have on oligodendrocyte development and their generation of myelin, a complex insulating membrane that not only facilitates rapid impulse conduction but also participates in mechanisms of brain plasticity and adaptation. Information is examined in relation to the importance of endogenous opioid function, as well as direct and indirect effects of opioid analogues, which like methadone and buprenorphine are used in medication-assisted therapies for opioid addiction during pregnancy and pharmacotherapy in neonatal abstinence syndrome. Potential opioid effects are also discussed regarding late myelination of the brain prefrontal cortex in adolescents and young adults. Such knowledge is fundamental for the design of safer pharmacological interventions for opioid abuse, minimizing deleterious effects in the developing nervous system.


Assuntos
Analgésicos Opioides/efeitos adversos , Encéfalo/crescimento & desenvolvimento , Endorfinas , Bainha de Mielina/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Feminino , Humanos , Síndrome de Abstinência Neonatal , Transtornos Relacionados ao Uso de Opioides/patologia , Gravidez
20.
Food Chem ; 362: 130262, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34118509

RESUMO

Infant biscuits (IBs) are commonly used during the complementary feeding of infants from the 6th month of life. They contain wheat flour and dairy ingredients, which can release the opioid-acting peptides ß-casomorphins (BCMs) and gluten exorphins (GEs) after gastrointestinal digestion. In the present study, five model IBs were prepared with or without gluten and different powdered milk derivatives in the formulations. IBs were digested simulating an in vitro static gastrointestinal digestion for infants aged 6-12 months. BCMs and GEs were identified and quantified by UPLC/HR-MS. The amounts of BCM7 and the GE A5 were related to the ß-CN and gluten content of the formulations. To date, levels of BCMs and GEs in digests of IBs have not been reported in literature. This work represents an in vitro investigation regarding the release of opioid-acting peptides in IBs. It could add additional knowledge on complementary foods for infant health.


Assuntos
Digestão , Endorfinas/metabolismo , Alimentos Infantis/análise , Peptídeos/química , Animais , Laticínios , Farinha , Glutens/química , Humanos , Lactente , Alimentos Infantis/normas , Leite/química , Peptídeos/análise , Peptídeos/metabolismo
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