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1.
Arq. ciências saúde UNIPAR ; 26(3): 1218-1228, set-dez. 2022.
Article in English | LILACS | ID: biblio-1414493

ABSTRACT

Bacteria that are resistant to several antibiotics are a serious One Health problem, as new alternatives for treatment do not appear at the same speed. Thus, the aim of this work was to carry out a survey of studies involving the activity of the essential oil of O. vulgare and its isolated compound carvacrol on antibiotic-resistant bacteria. To this end, a qualitative review of the literature was carried out in the PubMed database from 2015 to 2020. Both for the essential oil and for the isolated compound, the inhibitory action extends to strains often associated with difficult-to-treat infections such as oxacillin and vancomycin-resistant Staphylococcus aureus, ß-lactamase-producing strains, carbapenemases, among others. The point that distinguishes the studies is the type of methodology used in the tests, with studies with carvacrol more directed towards mechanisms of molecular action and application in cells and animals, while those with oils are more preliminary. Although these substances have potential to control resistant bacteria, more research is needed to enable their use.


Bactérias resistentes a vários antibióticos são um grave problema para a Saúde Única, pois novas alternativas de tratamento não aparecem na mesma velocidade. Assim, o objetivo deste trabalho foi realizar um levantamento de estudos envolvendo a atividade do óleo essencial de O. vulgare e seu composto isolado, carvacrol, sobre bactérias resistentes a antibióticos. Para tanto, foi realizada uma revisão qualitativa da literatura na base de dados PubMed no período de 2015 a 2020. Tanto para o óleo essencial quanto para o composto isolado, a ação inibitória se estende a cepas frequentemente associadas a infecções de difícil tratamento como Staphylococcus aureus resistente à oxacilina e vancomicina, cepas produtoras de ß-lactamase, carbapenemases, entre outras. O ponto que diferencia os estudos é o tipo de metodologia utilizada nos testes, sendo os estudos com carvacrol mais direcionados para mecanismos de ação molecular e aplicação em células e animais, enquanto os com óleos são mais preliminares. Embora essas substâncias tenham potencial para controlar bactérias resistentes, mais pesquisas são necessárias para viabilizar seu uso.


Las bacterias resistentes a diversos antibióticos son un grave problema para la Sanidad Única, ya que las nuevas alternativas de tratamiento no aparecen a la misma velocidad. Así pues, el objetivo de este trabajo fue realizar una encuesta sobre los estudios relativos a la actividad del aceite esencial de O. vulgare y su compuesto aislado, el carvacrol, sobre las bacterias resistentes a los antibióticos. Para ello, se realizó una revisión bibliográfica cualitativa en la base de datos PubMed en el periodo comprendido entre 2015 y 2020. Tanto para el aceite esencial como para el compuesto aislado, la acción inhibidora se extiende a cepas frecuentemente asociadas a infecciones de difícil tratamiento como el Staphylococcus aureus resistente a la oxacilina y a la vancomicina, cepas productoras de ß-lactamasas, carbapenemasas, entre otras. El punto que diferencia los estudios es el tipo de metodología utilizada en las pruebas, siendo los estudios con carvacrol más dirigidos a mecanismos de acción molecular y aplicación en células y animales, mientras que los de aceites son más preliminares. Aunque estas sustancias tienen potencial para controlar las bacterias resistentes, es necesario seguir investigando para que su uso sea viable.


Subject(s)
Oils, Volatile/therapeutic use , Origanum/drug effects , Oxacillin/therapeutic use , Plants, Medicinal/drug effects , Staphylococcus aureus/drug effects , Vancomycin/therapeutic use , Vancomycin-Resistant Staphylococcus aureus/pathogenicity , Anti-Bacterial Agents/therapeutic use
2.
Psicol. Estud. (Online) ; 27: e47800, 2022.
Article in Portuguese | LILACS, Index Psychology - journals | ID: biblio-1365263

ABSTRACT

RESUMO A ludoterapia de orientação humanista de Axline se baseia no pressuposto de que o jogo é a maneira natural da criança se expressar. Contudo, essa abordagem parece apresentar algumas lacunas éticas no que diz respeito à relação da criança com o Outro. Tais lacunas foram discutidas a partir do pensamento do filósofo Emmanuel Lévinas, que tratou da ética da alteridade radical. Neste sentido, este trabalho reflete como a ética levinasiana pode se manifestar não só na ludoterapia, mas também na prática clínica, por meio de uma pesquisa qualitativa com metodologia de estudo de caso. O grupo terapêutico aconteceu em 14 sessões de aproximadamente uma hora e era formado por três crianças de 5 a 7 anos. As sessões foram descritas de forma narrativa e a terapeuta escreveu, a partir delas, as suas Versões de Sentido. Ademais, foram realizadas anamneses, devolutivas, entrevistas com outros profissionais da saúde e visitas escolares. As sessões foram analisadas a partir da descrição e compreensão dos sentidos. Verificou-se que o processo grupal pareceu caminhar para uma maior abertura e proximidade entre os participantes do grupo e que a terapeuta precisou ir em direção à criança, isto é, demonstrar abertura à sua diferença. Concluiu-se que, ao entrar na brincadeira junto à criança, o psicoterapeuta não pôde apreender o mundo infantil, mas apenas cumprir com o seu dever ético e inferir que o encontro com as crianças em terapia significa descobrir a diferença pela via traumática. Ressaltou-se, além disso, a dificuldade em teorizar sobre a criança ou a infância, visto que ambas só têm sentido enquanto for fomentado o respeito à alteridade.


RESUMEN La Terapia de Juego humanista de Axline se basa en la suposición de que jugar es la forma natural del niño de expresarse. Sin embargo, este enfoque parece presentar lagunas éticas con respecto a la relación del niño con los demás. Estas lagunas se discutieron a partir de los pensamientos de Emmanuel Lévinas, un filósofo que escribió sobre la ética de la alteridad radical. En este sentido, se discutió cómo la ética de Lévinas puede verse en la terapia de juegos, incluida la práctica clínica. La investigación fue cualitativa con una metodología de estudio de caso. El grupo se realizó en 14 reuniones terapéuticas de una hora de duración y estuvo formado por tres niños de 5 a 7 años. Las reuniones se describieron en forma narrativa y la terapeuta escribió, a partir de ellas, sus Versiones de Significado. Además, se realizó anamnesis, devolutivos, entrevistas con otros profesionales de la salud y visitas escolares. Las sesiones se analizaron a partir de la descripción y comprensión de los sentidos. Fue posible verificar que el proceso del grupo se dirigió hacia una mayor apertura y proximidad entre los participantes del grupo, y que la terapeuta tuvo que dirigirse hacia los niños,es decir, demostrar apertura a su diferencia. Se concluyó que, al entrar en el juego con el niño, el psicoterapeuta no puede apoderarse del mundo de los niños, sino cumplir el deber ético; y reunirse con los niños en terapia era encontrar la diferencia a través de una forma traumática. Además, se destacó la dificultad para teorizar sobre el niño o la infancia, ya que ambos solo tienen sentido si se fomenta el respeto por la alteridad.


ABSTRACT Axline's humanistic-oriented Play Therapy assumes that play is a child's natural way of expressing herself. However, this approach seems to present some ethical gaps when thought concerning the relationship with others. Such gaps were discussed based on Emmanuel Lévinas' thoughts, a philosopher who wrote about radical otherness ethics. In this sense, it was necessary to reflect on how Levinasian ethics can be manifested in Play Therapy, including clinical practice. The research was qualitative, with a case study methodology. The therapeutic group took place in 14 sessions and consisted of three children, aged 5 to 7, with a one-hour meeting. The sessions were described narratively, and the Sense's Version of the therapist was written. Anamnesis, feedback, interviews with other health professionals and school visits were also conducted. The sessions were analyzed based on the description and understanding of meanings. It was found that the group process seemed to move towards greater openness and proximity among the participants and that the therapist needed to move towards the children, opening up to their differences. It was concluded that, when entering the play with the child, the psychotherapist cannot apprehend the child's world but only fulfill her ethical duty and meeting herself with the children in therapy was facing the difference through a traumatic via. It is noteworthy that it is difficult to theorize about childhood, and the theory will only make sense while promoting respect to otherness.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Play Therapy , Play and Playthings/psychology , Psychology , Therapeutics/psychology , Behavior , Aggression/psychology , Emotions , Ethics , Psychotherapists/psychology
3.
Microsc Res Tech ; 84(3): 441-459, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32959456

ABSTRACT

Tillandsia is the bromeliad genus containing the largest number of species, with wide geographic dispersion and an important ecological role in the ecosystems. Investigations of pollen morphology are important to support taxonomic and conservation studies as well as to choose promising species for cross-pollination to obtain hybrids. The objective of this study was to evaluate the morphology, production, and viability of pollen grains of 24 Tillandsia species that naturally occur in the state of Bahia, Brazil. Pollen grains were acetolized and analyzed by scanning electron microscopy. The pollen were germinated in vitro in two culture media (BM and BKM) and collected at three floral development stages (pre-anthesis, anthesis and post-anthesis). Pollen viability also was analyzed by staining with Alexander's solution and acetocarmine in three floral development stages. Variations in the ornamentation and size of the pollen were observed among the species studied, with the majority having medium size, while T. polystachia and T. juncea had large grains and the subgenera Diaphoranthema and Phytarrhiza had small grains. The pollen of the majority of species had bilateral symmetry, with a single irregularly shaped colpus, semitectate exine and reticulated-heterobrochate surface. The pollen presented high germination percentage, tube length and viability according to the histochemistry, except for T. recurvata, T. usneoides and T. loliacea. The BKM medium and collection of pollen during anthesis produced the best results for the Tillandsia species. The results can support studies of the taxonomy and conservation of these species, which have great environmental importance and high value for ornamental purposes.


Subject(s)
Bromeliaceae , Tillandsia , Ecosystem , Microscopy, Electron, Scanning , Pollen
4.
Brain Res Bull ; 164: 214-220, 2020 11.
Article in English | MEDLINE | ID: mdl-32858126

ABSTRACT

In the neonate, the main mediator for satiety or hunger is the information of distention or gastric contraction. Food intake controls has two types of a short-term one, based on the level of hydration, and another long-term one, dependent on the gastric stretch. The aim of this study is to evaluate the gene expression of peptides and nutrient sensors in the hypothalamus at 10 and 18 days of postnatal life. Male rats divided into groups: Fasting, Water, Milk, and Gavage.Two age groups had analyzed into 10 and 18 days. Gene expression of hypothalamic peptides, Neuropeptide Y(NPY), Agouti-related peptide(AgRP), proopiomelanocortin(POMC), cocaine-and amphetamine-regulated transcript(CART), and energy sensors mechanistic target of rapamycin(mTOR) and AMP-activated protein kinase(AMPK) in the hypothalamus was seen. During the fasting period, there was an increase in expression of AMPK seen in 10 and 18 days, also mTOR reduction. Expression of NPY, AgRP, and POMC suffered the fasting effect only at 18 days. The effect of gastric distention and energy loads, there was increased expression of AMPK at 10 and 18 days, but expression of mTOR showed only at 18 days. There was increased NPY expression at 18 days, but not at 10 days, while AgRP increased its expression at both ages. At 10 days gene expression of CART increased and POMC as well as 10-18 days. Data demonstrated a simultaneous responsiveness to hypothalamic nutrient sensing also, controlling peptide food consumption even at an early age. The mature standard of control only observed at 18 days of life.


Subject(s)
Agouti-Related Protein/metabolism , Hypothalamus/metabolism , Nerve Tissue Proteins/metabolism , Neuropeptide Y/metabolism , Pro-Opiomelanocortin/metabolism , Agouti-Related Protein/genetics , Animals , Animals, Newborn , Gene Expression , Nerve Tissue Proteins/genetics , Neuropeptide Y/genetics , Pro-Opiomelanocortin/genetics , Rats , Rats, Wistar
5.
Pharmacol Biochem Behav ; 192: 172908, 2020 05.
Article in English | MEDLINE | ID: mdl-32199909

ABSTRACT

Stressful events occurring during early life have been related to behavioral and neurochemical disturbances. Maternal separation during the first two weeks of life is a traumatic event that strongly affects the feeding behavior and serotonergic system of the progeny in adulthood. As this system modulates the feeding behavior, the present study aimed at investigating the effects of maternal separation-induced stress on both the feeding behavior and serotonergic system of the middle-aged female rats by manipulating this system using fluoxetine, a selective serotonin transporter inhibitor. Lactating Wistar rats were separated from their litters from postnatal day 2 (PND 2) to PND 14 for 3 h in the dark phase of the circadian cycle. The maternally separated (MS) and control (C) groups were distinguished from each other based on the incidence or absence of maternal separation (early life stress). All the analyses were done on the female offspring from one-year of age. Maternal separation anticipated the satiety point in these females. This anticipation was linked to lower food intake, meal duration and meal size. These results mirrored the effects of fluoxetine in the control animals. Furthermore, maternal separation was associated with 5ht1b serotonin receptor hyperexpression in the hypothalamus. These findings demonstrate that maternal separation has long-lasting effects on the eating behavior and serotonergic system and that this system could be responsible for mediating these behavioral outcomes.


Subject(s)
Eating/drug effects , Feeding Behavior/drug effects , Maternal Deprivation , Receptor, Serotonin, 5-HT1B/genetics , Receptor, Serotonin, 5-HT2C/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Stress, Psychological , Animals , Animals, Newborn , Behavior, Animal/drug effects , Female , Fluoxetine/pharmacology , Gene Expression , Hypothalamus/metabolism , Lactation , Male , RNA/genetics , Rats , Rats, Wistar , Receptor, Serotonin, 5-HT1B/metabolism , Receptor, Serotonin, 5-HT2C/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology
6.
Int J Dev Neurosci ; 80(3): 209-219, 2020 May.
Article in English | MEDLINE | ID: mdl-32083748

ABSTRACT

Early life stress (ELS) has been associated with developmental impairments. Early weaning (EW) is a postnatal stress model consisting of interruption of lactation and maternal care. The 5HT-system has been associated with neurobehavioral modulations promoted by ELS. Thus, the present work aims to investigate the effects of early weaning on feeding behavior and serotonergic system of juvenile male rats. For this, rats were submitted to early (PND15) or natural (PND30) weaning and had the body weight, food intake in circadian phases, and food intake in response to fenfluramine assessed. mRNA expression of serotoninergic receptors (5HT1A and 5HT2C) and transporter (SERT) was assessed in the hypothalamus and brainstem, as well as NPY and POMC mRNA expression in hypothalamus. The results show that early weaning promoted changes in the percentage of weight gain during lactation period and increase in body weight at PND40. It was also observed that EW promoted increase and decrease in food intake in light and dark phase, respectively, and leads to a decreased action of fenfluramine on inhibition of food intake. In addition, early weaning promoted increased NPY and SERT mRNA expression in the hypothalamus and 5HT2C in the brainstem. Together, the data indicate that the stress caused by early weaning impairs the eating behavior of juvenile male rats through hypofunction of the 5HT-system.


Subject(s)
Brain Stem/metabolism , Feeding Behavior/physiology , Hypothalamus/metabolism , Receptors, Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin/metabolism , Weaning , Animals , Body Weight/physiology , Circadian Rhythm/physiology , Eating/physiology , Male , Rats , Rats, Wistar
7.
Behav Brain Res ; 383: 112531, 2020 04 06.
Article in English | MEDLINE | ID: mdl-32014554

ABSTRACT

Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5HT and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5HT and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5HT1B, 5HT2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5HT1B mRNA expression. In the brainstem, the expression of 5HT1B, SERT, 5HT2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5HT and DA systems.


Subject(s)
Feeding Behavior/physiology , Hyperphagia/physiopathology , Hypothalamus/metabolism , RNA, Messenger/metabolism , Weaning , Animals , Body Weight , Dopamine/metabolism , Hyperphagia/metabolism , Male , Rats , Receptor, Serotonin, 5-HT1B/genetics , Receptor, Serotonin, 5-HT1B/metabolism , Receptor, Serotonin, 5-HT2C/genetics , Receptor, Serotonin, 5-HT2C/metabolism , Receptors, Dopamine D1/genetics , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism
8.
Behav Processes ; 170: 103981, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31682870

ABSTRACT

Convergent evidence in literature shows that rapid disruption of maternal care and breastfeeding due to an early weaning protocol changes the development of several neurobehavioral patterns in rodents, including the circadian pattern of feeding. The serotoninergic system has been associated with the control of feeding patterns. Therefore, we aim to evaluate the patterns of feeding, the mRNA expression of 5 H T-1b, 5 H T-2c, and SERT on the hypothalamus, brainstem, and the body weight of female juvenile Wistar rats, submitted to early (PND15) or regular (PND30) weaning. The results demonstrate that early weaning promotes an increase in food intake in a 24 -h period, in the dark phase of the circadian cycle and in the four-hour time intervals at the beginning of the dark and light phases. Also, early weaning decreases the mRNA expression of 5 H T-1b, 5 H T-2c, and SERT on the hypothalamus, but increases it on the brainstem. Additionally, early weaning promotes an increase in body weight. Therefore, the present data demonstrate that early weaning changes the patterns of feeding in juvenile female rats and suggests that this behavioral modification is due to the modulations promoted in the 5 H T-system.


Subject(s)
Feeding Behavior/physiology , Serotonin/physiology , Weaning , Animals , Body Weight/genetics , Brain/anatomy & histology , Brain Stem/metabolism , Circadian Rhythm , Eating/physiology , Energy Intake/genetics , Female , Hypothalamus/metabolism , Maternal Behavior , Organ Size/genetics , RNA, Messenger/biosynthesis , RNA-Binding Proteins/genetics , Rats , Rats, Wistar
9.
Behav Brain Res ; 357-358: 65-70, 2019 01 14.
Article in English | MEDLINE | ID: mdl-28756214

ABSTRACT

The neurotransmitter serotonin (5-HT) acts as an important regulator of the critical neurodevelopmental processes and thus alterations in 5-HT signaling early promotes permanent structural and functional changes in brain. The selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram, blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the neurodevelopmental period may alters 5-HT signaling sensitivity on food intake control. The aim of the present study was to evaluate the effects of neonatal exposure to fluoxetine on molecular and cellular components of the serotonergic system and food intake control in young animals. Methods: The animals were divided according to experimental manipulation, Fluoxetine Group (FG): male pups received application of fluoxetine (10 mg/kg, 10 µL/g) and Saline Group (SG): male pups received saline application (0.9% NaCl, 10 µL/g), both throughout lactation (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein expression, serotonin content in the hypothalamus. The neonatal exposure to fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic response, and increase the serotonin and SERT hypothalamic in young animals. We conclude that the changes of components of the serotonergic system by neonatal exposure to fluoxetine may be responsible for disturb the inhibitory action of serotonin on food intake.


Subject(s)
Eating/drug effects , Fluoxetine/pharmacology , Neural Inhibition/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin/metabolism , Synaptic Transmission/drug effects , Age Factors , Animals , Animals, Newborn , Body Weight/drug effects , Citalopram/pharmacology , Female , Food Deprivation , Gene Expression Regulation/drug effects , Hypothalamus/cytology , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar , Serotonin Plasma Membrane Transport Proteins/genetics
10.
Nutrients ; 10(7)2018 Jul 20.
Article in English | MEDLINE | ID: mdl-30037019

ABSTRACT

Fatty acid (FA) composition is a determinant of the physiological effects of dietary oils. This study investigated the effects of vegetable oil supplementation with different FA compositions on anthropometric and biochemical parameters in obese women on a hypocaloric diet with lifestyle modifications. Seventy-five women (body mass index, BMI, 30⁻39.9kg/m²) were randomized based on 8-week oil supplementation into four experimental groups: the coconut oil group (CoG, n = 18), the safflower oil group (SafG, n = 19), the chia oil group (ChG, n = 19), and the soybean oil placebo group (PG, n = 19). Pre- and post-supplementation weight, anthropometric parameters, and body fat (%BF), and lean mass percentages (%LM) were evaluated, along with biochemical parameters related to lipid and glycidemic profiles. In the anthropometric evaluation, the CoG showed greater weight loss (Δ% = -8.54 ± 2.38), and reduced BMI (absolute variation, Δabs = -2.86 ± 0.79), waist circumference (Δabs = -6.61 ± 0.85), waist-to-height ratio (Δabs = -0.041 ± 0.006), conicity index (Δabs = -0.03 ± 0.016), and %BF (Δabs = -2.78 ± 0.46), but increased %LM (Δabs = 2.61 ± 1.40) (p < 0.001). Moreover, the CoG showed a higher reduction in biochemical parameters of glycemia (Δabs = -24.71 ± 8.13) and glycated hemoglobin (Δabs = -0.86 ± 0.28) (p < 0.001). The ChG showed a higher reduction in cholesterol (Δabs = -45.36 ± 0.94), low-density lipoprotein cholesterol (LDLc; Δabs = -42.53 ± 22.65), and triglycerides (Δabs = -49.74 ± 26.3), but an increase in high-density lipoprotein cholesterol (HDLc; abs = 3.73 ± 1.24, p = 0.007). Coconut oil had a more pronounced effect on abdominal adiposity and glycidic profile, whereas chia oil had a higher effect on improving the lipid profile. Indeed, supplementation with different fatty acid compositions resulted in specific responses.


Subject(s)
Cholesterol/blood , Cocos/chemistry , Diet, Reducing , Fatty Acids/pharmacology , Obesity/blood , Plant Oils/pharmacology , Salvia/chemistry , Adipose Tissue/metabolism , Adult , Blood Glucose/metabolism , Body Composition/drug effects , Body Mass Index , Carthamus tinctorius/chemistry , Coconut Oil/metabolism , Coconut Oil/therapeutic use , Dietary Fats, Unsaturated/blood , Dietary Supplements , Fatty Acids/blood , Fatty Acids/therapeutic use , Female , Humans , Obesity/diet therapy , Obesity, Abdominal/blood , Obesity, Abdominal/diet therapy , Plant Oils/chemistry , Plant Oils/metabolism , Plant Oils/therapeutic use , Glycine max/chemistry , Waist Circumference , Weight Loss/drug effects
11.
Diabetes ; 67(2): 299-308, 2018 02.
Article in English | MEDLINE | ID: mdl-29097375

ABSTRACT

Insulin has a narrow therapeutic index, reflected in a small margin between a dose that achieves good glycemic control and one that causes hypoglycemia. Once injected, the clearance of exogenous insulin is invariant regardless of blood glucose, aggravating the potential to cause hypoglycemia. We sought to create a "smart" insulin, one that can alter insulin clearance and hence insulin action in response to blood glucose, mitigating risk for hypoglycemia. The approach added saccharide units to insulin to create insulin analogs with affinity for both the insulin receptor (IR) and mannose receptor C-type 1 (MR), which functions to clear endogenous mannosylated proteins, a principle used to endow insulin analogs with glucose responsivity. Iteration of these efforts culminated in the discovery of MK-2640, and its in vitro and in vivo preclinical properties are detailed in this report. In glucose clamp experiments conducted in healthy dogs, as plasma glucose was lowered stepwise from 280 mg/dL to 80 mg/dL, progressively more MK-2640 was cleared via MR, reducing by ∼30% its availability for binding to the IR. In dose escalations studies in diabetic minipigs, a higher therapeutic index for MK-2640 (threefold) was observed versus regular insulin (1.3-fold).


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Drug Design , Hypoglycemic Agents/therapeutic use , Insulin, Regular, Human/analogs & derivatives , Lectins, C-Type/agonists , Mannose-Binding Lectins/agonists , Receptor, Insulin/agonists , Receptors, Cell Surface/agonists , Animals , Animals, Inbred Strains , Binding, Competitive , CHO Cells , Cricetulus , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/metabolism , Dogs , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Half-Life , Humans , Hyperglycemia/prevention & control , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacokinetics , Insulin, Regular, Human/adverse effects , Insulin, Regular, Human/pharmacokinetics , Insulin, Regular, Human/therapeutic use , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Ligands , Male , Mannose Receptor , Mannose-Binding Lectins/genetics , Mannose-Binding Lectins/metabolism , Metabolic Clearance Rate , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Recombinant Proteins/adverse effects , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Swine , Swine, Miniature
12.
Physiol Behav ; 165: 35-42, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27364433

ABSTRACT

In neonatal rats, hunger and satiety responses occur particularly via dehydration and gastric distention, respectively. The control of food intake in newborns is yet to be fully consolidated, particularly with respect to the participation of the hypothalamic nuclei and their relationship with the serotonergic pathway. Moreover, it is unclear how the environmental stressors in early life, like undernutrition, interfere in these events. Therefore, this study examined the serotonin-system's impact on food intake in rat neonates at postnatal day (P) 10 and P18 and the manner in which protein undernutrition during pregnancy and lactation interferes in this behavior. To accomplish this, Wistar rats were used, nutritionally manipulated by a diet having two protein levels, (8% and 17%) during pregnancy and lactation, to form the Control (n=10) and Low protein groups (n=10). At 10 and 18 postnatal days pups received an acute dose of fenfluramine (3mg/kg) or saline (0.9% NaCl) and subjected to milk consumption testing and then perfused to obtain the brains for the analysis of cell activation of the immunoreactive c-Fos in the hypothalamic and raphe nuclei. At 10days a reduction in weight gain was observed in both groups. On comparison of the neuronal activation for the paraventricular nucleus, an increased activation in response to fenfluramine was observed. At 18days, the weight gain percentage differed between the groups according to the nutritional manipulation, in which the control animals had no significant change while the undernourished presented increased weight gain with the use of fenfluramine. The marking of c-Fos in response to fenfluramine in the hypothalamic and raphe nuclei revealed, an especially lower activation of the PVN, MnR and DR compared intra-group. However when evaluating the effect of undernutrition, marking activation was observed to increase in all the nuclei analyzed, in the hypothalamus and raphe. Data from this study indicate that the action of serotonin via food intake in the neonates may have been delayed by early protein undernutrition.


Subject(s)
Diet, Protein-Restricted/adverse effects , Eating/physiology , Hypothalamus/physiology , Malnutrition/physiopathology , Raphe Nuclei/physiology , Serotonin/metabolism , Animals , Animals, Newborn , Disease Models, Animal , Eating/drug effects , Female , Fenfluramine/pharmacology , Fetal Nutrition Disorders/metabolism , Fetal Nutrition Disorders/physiopathology , Hypothalamus/drug effects , Hypothalamus/growth & development , Lactation , Male , Milk , Neurons/drug effects , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Raphe Nuclei/drug effects , Raphe Nuclei/growth & development , Rats, Wistar , Selective Serotonin Reuptake Inhibitors/pharmacology , Weight Gain/drug effects , Weight Gain/physiology
13.
Int J Dev Neurosci ; 46: 76-81, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26287581

ABSTRACT

BACKGROUND: Serotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood. OBJECTIVES: Investigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C). METHODS: In each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to the 21(st) postnatal day, C pups received sterile saline while F pups received fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC). RESULTS: The use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC. CONCLUSIONS: These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats.


Subject(s)
Gene Expression Regulation, Developmental/physiology , Hypothalamus/metabolism , Serotonin/metabolism , Adipose Tissue/drug effects , Adipose Tissue/pathology , Age Factors , Animals , Animals, Newborn , Body Weight/drug effects , Cholesterol/blood , Diet/adverse effects , Eating/drug effects , Female , Fluoxetine/pharmacology , Gene Expression Regulation, Developmental/drug effects , Hypothalamus/drug effects , Male , Neuropeptide Y/genetics , Neuropeptide Y/metabolism , Pregnancy , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , Rats , Rats, Wistar , Selective Serotonin Reuptake Inhibitors/pharmacology , Triglycerides/blood
14.
Can J Physiol Pharmacol ; 92(4): 330-7, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24708216

ABSTRACT

The brain, more than any other organ in the body, is vulnerable to oxidative stress damage, owing to its requirement for high levels of oxygenation. This is needed to fulfill its metabolic needs in the face of relatively low levels of protective antioxidants. Recent studies have suggested that oxidative stress is directly involved in the etiology of both eating and anxiety behavior. The aim of this study was to evaluate the effect of fluoxetine-inhibited serotonin reuptake in nursing rat neonates on behavior and on oxidative stress in the hypothalamus and the hippocampus; brain areas responsible for behavior related to food and anxiety, respectively. The results show that increased serotonin levels during a critical period of development do not induce significant differences in food-related behavior (intake and satiety), but do result in a in a significant decrease in anxiety. Measurements of oxidative stress showed a significant reduction of lipid peroxidation in the hippocampus (57%). In the hypothalamus, antioxidant enzymes were unchanged, but in the hippocampus, the activity of catalase and glutathione-S-transferase was increased (80% and 85% respectively). This suggests that protecting neural cells from oxidative stress during brain development contributes to the anxiolytic effects of serotonin.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety/prevention & control , Behavior, Animal/drug effects , Fluoxetine/therapeutic use , Hippocampus/drug effects , Oxidative Stress/drug effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Animals , Animals, Newborn , Anti-Anxiety Agents/pharmacology , Anxiety/metabolism , Anxiety/psychology , Behavior, Animal/physiology , Body Weight/drug effects , Eating/drug effects , Fluoxetine/pharmacology , Hippocampus/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Lipid Metabolism/drug effects , Rats , Rats, Wistar , Serotonin/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology
15.
Bioelectrochemistry ; 85: 56-60, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22197266

ABSTRACT

This work reports the isolation of Microgramma vaccinifolia rhizome lectin (MvRL) and the determination of electrochemical potentials of MvRL in the presence of Ca²âº, Mg²âº and human type O erythrocytes. MvRL showed the highest specific hemagglutinating activity with human type O erythrocytes and showed a single polypeptide band of 17 kDa on SDS-PAGE. MvRL hemagglutinating activity was neutralized after dialysis with EDTA, and addition of Ca²âº and Mg²âº restored the activity. Electrochemical potentials of MvRL in the presence of 100 mM Ca²âº (882 mV) and 60 mM Mg²âº (1051 mV) were higher (p<0.05) than in the presence of only 0.15 M NaCl (247 mV), indicating that the electrochemical system was sensitive to structural and physico-chemical changes promoted by these ions. MvRL potential did not change in the presence of type O erythrocytes. The electrochemical system was able to detect changes in electrochemical potentials of MvRL promoted by Ca²âº and Mg²âº, even in a complex environment (human serum supplemented with 40 and 60mM of these ions). The study reveals that the stimulatory effect of Ca²âº and Mg²âº on hemagglutinating activity may be linked to conformational change and/or alterations in surface charge distribution of MvRL.


Subject(s)
Electrochemistry/methods , Lectins/chemistry , Rhizome/chemistry , Calcium , Erythrocytes , Hemagglutination , Humans , Lectins/isolation & purification , Magnesium , Protein Conformation
16.
Nutr Neurosci ; 13(6): 246-55, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21040622

ABSTRACT

The appearance, the odor, and the flavor of foods, all send messages to the encephalic area of the brain. The hypothalamus, in particular, plays a key role in the mechanisms that control the feeding behavior. These signals modulate the expression and the action of anorexigenic or orexigenic substances that influence feeding behavior. The serotonergic system of neurotransmission consists of neurons that produce and liberate serotonin as well as the serotonin-specific receptor. It has been proven that some serotonergic drugs are effective in modulating the mechanisms of control of feeding behavior. Obesity and its associated illnesses have become significant public health problems. Some drugs that manipulate the serotonergic systems have been demonstrated to be effective interventions in the treatment of obesity. The complex interplay between serotonin and its receptors, and the resultant effects on feeding behavior have become of great interest in the scientific community.


Subject(s)
Feeding Behavior/physiology , Serotonin/physiology , Animals , Cholecystokinin/physiology , Energy Metabolism/physiology , Feeding Behavior/drug effects , Homeostasis , Humans , Hypothalamus/physiology , Neurons/physiology , Neuropeptide Y/physiology , Pro-Opiomelanocortin/physiology , Receptors, Serotonin/physiology , Synaptic Transmission
17.
PLoS One ; 5(10): e13537, 2010 Oct 21.
Article in English | MEDLINE | ID: mdl-20975839

ABSTRACT

BACKGROUND: Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in the adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through pregnancy and lactation. From a total of 26 209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Further bioinformatic analysis of the data revealed that perinatal protein restriction permanently alters the expression of two gene clusters regulating common cellular processes. The first one includes several gate keeper genes regulating insulin signaling and nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. CONCLUSIONS/SIGNIFICANCE: Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable resource for further investigating the role of the hypothalamus in the programming of the metabolic syndrome.


Subject(s)
Diet , Energy Metabolism , Homeostasis , Hypothalamus/metabolism , Animals , Female , Gene Expression Profiling , Male , Rats , Rats, Sprague-Dawley , Signal Transduction , Transcription, Genetic
18.
An. Fac. Med. Univ. Fed. Pernamb ; 50(2): 132-137, 2005. ilus, graf
Article in Portuguese | LILACS | ID: lil-443342

ABSTRACT

RESUMO: Durante o período crítico de desenvolvimento do sistema nervoso, o organismo é vulnerável a agressões de diversas naturezas, que podem acarretar transtornos morfofuncionais na vida adulta. A construção do comportamento alimentar é vulnerável a estas agressões, sendo importante para a sobrevivência da espécie e, portanto, alvo de estudos. O objetivo deste trabalho foi estudar o efeito da manipulação farmacológica do sistema noradrenérgico, através da inibição da recaptação de noradrenalina, durante o período neonatal e as repercussões dessa agressão sobre o consumo alimentar, na vida adulta. Os animais foram tratados diariamente, durante os 21ºdias de vida com reboxetina (20mg/Kg de peso), um inibidor seletivo da recaptação de noradrenalina (NARI) ou solução salina (NaCI 0,9por cento). Aos 60 dias foi avaliado o consumo alimentar e a ingestão hídrica. Os animais tratados com salina. Concluímos que a agressão farmacológica do sistema noradrenérgico durante o perídoso neonatal, pode alterar de forma duradoura o consumo alimentar e a ingestão hídrica. Essas alterações sugerem que o tratamento pode alterar morfofucionalmente estruturas relacionadas a regulação do comportamento alimentar e da ingestão hídrica, levando a alterações comportamentais na vida adulta


Subject(s)
Animals , Adult , Rats , Breast Feeding , Drinking , Eating , Adrenergic Uptake Inhibitors/therapeutic use , Norepinephrine , Rats, Wistar , Body Weight , Data Interpretation, Statistical , Infant, Newborn/metabolism
19.
J. bras. aids ; 4(2): 67-71, abr.-jun. 2003.
Article in Portuguese | LILACS, SES-SP | ID: lil-341876

ABSTRACT

O crescimento da epidemia de AIDS entre as mulheres levou, consequentemente, ao aumento do numero de casos em criancas, pois a grande maioria e devido a transmissao vertical do hiv, cuja probalidade de ocorrencia foi demonstrada em varios estudos. Foi evidenciado que a maioria dos casos, cerca de 65 porcento, ocorre durante o trabalho de parto e no parto propriamente dito e os 35 porcento restantes ocorrem intra-utero, principalmente nas ultimas semanas de gestacao; o aleitamento materno representa risco adicional de transmissao de 7 porcento a 22 porcento. A evidencia de transmissao do HIV pela amamentacao levou o Ministerio da Saude a contra-indicar o aleitamento materno por mulheres portadoras do HIV, assim como o aleitamento cruzado (feito por outra mulher). O presente artigo apresenta consideracoes sobre a utilizacao do teste rapido para pesquisa do HIV nas parturientes e sobre a importancia da supressao da lactacao nas mulheres HIV+, descrevendo os metodos que podem ser recomendados


Subject(s)
Breast Feeding , HIV , Infectious Disease Transmission, Vertical , Suppression
20.
Distúrb. comun ; 13(1): 85-96, 2001.
Article in Portuguese | Index Psychology - journals | ID: psi-19770

ABSTRACT

Discute o papel do psicanalista na escola, a partir das possíveis articulações entre psicanálise e educação, durante um estágio de observação feito numa escola de educação infantil para crianças surdas, situada na cidade de São Paulo. A partir disso, acrescentamos algumas considerações buscando similaridades e diferenças na escola para cianças ouvintes e para crianças surdas. Dentro desse contexto, consideramos que a psicanálise pode intervir, visando tanto esclarecer as necessárias conseqüências dessa especificidade, quando buscar possíveis vias de restituir, no laço pais ouvintes filho surdo, a transmissão das marcas que o constituem para além do signo da surdez (AU)


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Deafness , Persons With Hearing Impairments , Education, Special
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