RESUMEN
Neisseria gonorrhoeae bacteria are acknowledged as an urgent threat to human health because this species has developed resistances to all of the antibiotics used clinically to treat its infections. N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, but also causes blindness when the bacteria infect the eyes. Infants are particularly susceptible, acquiring the infection from their mothers at birth. We have shown that the monoglyceride monocaprin rapidly kills N. gonorrhoeae and other bacterial species and is non-irritating in ocular assays. Here we show that the physical and chemical properties of monocaprin make it ideal for use in a thickened eye drop formulation to combat eye infections. Monocaprin-containing formulations were assessed using analytical techniques and for antimicrobial activity in vitro and in ex vivo infections. Monocaprin-containing formulations retained activity after three years and are non-irritating, unlike preparations of povidone iodine in our assays. A recommended formulation for further development and investigation is 0.25% monocaprin in 1% HPMC with 1% polysorbate 20.
Asunto(s)
Antibacterianos/uso terapéutico , Ceguera/tratamiento farmacológico , Composición de Medicamentos/métodos , Farmacorresistencia Bacteriana/efectos de los fármacos , Glicéridos/uso terapéutico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Soluciones Oftálmicas/uso terapéutico , Animales , Antibacterianos/farmacología , Ceguera/microbiología , Bovinos , Córnea/efectos de los fármacos , Córnea/microbiología , Glicéridos/farmacología , Gonorrea/microbiología , Pruebas de Sensibilidad Microbiana , Soluciones Oftálmicas/farmacologíaRESUMEN
OBJECTIVE: The main objective of the present study was to investigate the possible osteostimulatory action of recombinant human matrix metalloproteinase-2 (rhMMP-2) implanted in a bone defect made in calvaria of rats, bounded to the monoolein as carrier. METHODS: Forty-four adult male Wistar rats (about 600 g body weight) underwent surgery in order to create a spherical defect in parietal bone on the right side of the median sagittal suture by using 4 mm diameter of a trephine drill. Animals were divided into three groups: no treatment (control, C), treatment with rhMMP-2 diluted in monoolein liquid crystal (rhMMP-2) and negative control with monoolein (M). The groups were divided into two experimental times, 2- and 4-weeks of experimental time. RESULTS: The rate of new-formed bone, estimated by the number of points on new-formed cancellous bone, was in enhanced rhMMP-2 group in both periods in comparison to C or M groups. CONCLUSION: There was no difference in bone neoformation between second to fourth week within groups. In the present study, monoolein alone had a negative role in the post-operative surgery, but monoolein associated with +rhMMP-2 had a positive role on releasing rhMMP-2 and enhance the rate of new-formed bone (Tab. 1, Fig. 5, Ref. 71).
Asunto(s)
Regeneración Ósea , Glicéridos , Metaloproteinasa 2 de la Matriz , Proteínas Recombinantes , Adulto , Animales , Glicéridos/farmacología , Glicéridos/uso terapéutico , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/farmacología , Ratas , Ratas Wistar , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéuticoRESUMEN
Endocannabinoids protect against seizures, but their mechanism of action is still unclear, as they can have effects independent of known cannabinoid receptors. Using Drosophila melanogaster, which lacks canonical cannabinoid receptors, we report that the endocannabinoids anandamide and 2-arachidonoylglycerol protect against seizures in multiple fly seizure models. Surprisingly, inhibition of anandamide catabolism renders flies insensitive to protection by anandamide, indicating that anandamide metabolites are responsible for seizure protection. Consistent with this finding, arachidonic acid, a direct metabolite of anandamide, protects against seizures. To identify downstream effectors, we test for a role of transient receptor potential (TRP) channels and find that the TRPV1 antagonist capsazepine blocks the protective effect of anandamide. Also, a targeted genetic screen of TRP channels identifies water witch as a mediator of protection by anandamide. Using a Drosophila model, we reveal the role of arachidonic acid in seizure protection and identify a cannabinoid-receptor-1/2-independent mechanism of endocannabinoid seizure protection.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Ácidos Araquidónicos/uso terapéutico , Proteínas de Drosophila/metabolismo , Endocannabinoides/uso terapéutico , Glicéridos/uso terapéutico , Convulsiones/prevención & control , Canales de Potencial de Receptor Transitorio/metabolismo , Animales , Ácidos Araquidónicos/metabolismo , Calcio/metabolismo , Modelos Animales de Enfermedad , Proteínas de Drosophila/deficiencia , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Endocannabinoides/metabolismo , Alcamidas Poliinsaturadas/metabolismo , Alcamidas Poliinsaturadas/uso terapéutico , ARN Guía de Kinetoplastida/metabolismo , Receptor Cannabinoide CB1/metabolismo , Convulsiones/patología , Canales de Potencial de Receptor Transitorio/genéticaRESUMEN
The failure to undergo remyelination is a critical impediment to recovery in multiple sclerosis. Chondroitin sulfate proteoglycans (CSPGs) accumulate at demyelinating lesions creating a nonpermissive environment that impairs axon regeneration and remyelination. Here, we reveal a new role for 2-arachidonoylglycerol (2-AG), the major CNS endocannabinoid, in the modulation of CSPGs deposition in a progressive model of multiple sclerosis, the Theiler's murine encephalomyelitis virus-induced demyelinating disease. Treatment with a potent reversible inhibitor of the enzyme monoacylglycerol lipase, which accounts for 85% of the 2-AG degradation in the mouse CNS, modulates neuroinflammation and reduces CSPGs accumulation and astrogliosis around demyelinated lesions in the spinal cord of Theiler's murine encephalomyelitis virus-infected mice. Inhibition of 2-AG hydrolysis augments the number of mature oligodendrocytes and increases MBP, leading to remyelination and functional recovery of mice. Our findings establish a mechanism for 2-AG promotion of remyelination with implications in axonal repair in CNS demyelinating pathologies.SIGNIFICANCE STATEMENT The deposition of chondroitin sulfate proteoglycans contributes to the failure in remyelination associated with multiple sclerosis. Here we unveil a new role for 2-arachidonoylglycerol, the major CNS endocannabinoid, in the modulation of chondroitin sulfate proteoglycan accumulation in Theiler's murine encephalomyelitis virus-induced demyelinating disease. The treatment during the chronic phase with a potent reversible inhibitor of the enzyme monoacylglycerol lipase, which accounts for 85% of the 2-arachidonoylglycerol degradation in the mouse CNS, modulates neuroinflammation and reduces chondroitin sulfate proteoglycan deposition around demyelinated lesions in the spinal cord of Theiler's murine encephalomyelitis virus-infected mice. The increased 2-arachidonoylglycerol tone promotes remyelination in a model of progressive multiple sclerosis ameliorating motor dysfunction.
Asunto(s)
Ácidos Araquidónicos/farmacología , Ácidos Araquidónicos/uso terapéutico , Endocannabinoides/farmacología , Endocannabinoides/uso terapéutico , Glicéridos/farmacología , Glicéridos/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/fisiopatología , Fibras Nerviosas Mielínicas/efectos de los fármacos , Fibras Nerviosas Mielínicas/patología , Proteoglicanos/metabolismo , Animales , Agonistas de Receptores de Cannabinoides/farmacología , Agonistas de Receptores de Cannabinoides/uso terapéutico , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Femenino , Ratones , Esclerosis Múltiple/patología , Neurogénesis/efectos de los fármacosRESUMEN
INTRODUCTION: Oral microbiome impacts health and disease. T2DM and periodontitis are associated. Neem (Azadiracta indica) has antibacterial activity against oral microbiota. OBJECTIVES: To characterize oral microbiota (OMB) in saliva samples of T2DM patients by Next generation sequencing. To analyze MCP-1 levels among the T2DM patients before and after a month of neem stick usage as a toothbrush. MATERIALS AND METHODS: Blood and saliva samples were collected from adult T2DM patients before and after the neem stick usage. Metagenomic sequencing was performed on saliva samples targeting V6 region of 16s rRNA. Serum MCP-1 levels were determined using a quantitative sandwich Human MCP-1 standard ABTS development kit (Peprotech, USA). RESULTS: The profile of oral microbiota of T2DM patients (n=24) consists of Streptococcus (95.8%) counts ranging from 2644 to 27,214, Veillonella (72.2%, counts 25-19,709, Neisseria (87.5%) 453-33,445), Rothia (63.6%, 233-6734), Actinomycetes (25%, 161-3730), Fusobacterium (21%, 2252-21,334), and Pigmentiphaga (12.5% 3-16,644). Oral microbiota in healthy controls (n=10), consists of Streptococcus (26.1%), Veillonella (21.9%), Neisseria (16.9%), Haemophilus (10.7%), Actinomycetes (2.6%), Rothia (3.1%), Oribacterium (1.7%). Post neem samples showed drastic reduction in the load of bacteria which was statistically significant. The mean serum MCP-1 before the use of neem stick was 265.18±79.44 (range 141.6-980.5pg/ml) and dropped to 33.6±7.35 after a month of neem stick usage (P value>0.001). CONCLUSION: OMB of T2DM patients and healthy controls were similar, however bacterial loads were significantly higher in T2DM patients. Use of neem stick has a statistically significant reduction on bacterial loads and MCP-1 levels in T2DM patients.
Asunto(s)
Quimiocina CCL2/sangre , Diabetes Mellitus Tipo 2/microbiología , Glicéridos/uso terapéutico , Microbiota/efectos de los fármacos , Boca/microbiología , Terpenos/uso terapéutico , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/metabolismo , Saliva/microbiologíaRESUMEN
The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects.
Asunto(s)
Antipsicóticos/administración & dosificación , Benzodiazepinas/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanopartículas/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Animales , Antipsicóticos/efectos adversos , Antipsicóticos/química , Antipsicóticos/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/química , Benzodiazepinas/uso terapéutico , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/uso terapéutico , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Femenino , Glicéridos/administración & dosificación , Glicéridos/efectos adversos , Glicéridos/química , Glicéridos/uso terapéutico , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/uso terapéutico , Olanzapina , Polisorbatos/administración & dosificación , Polisorbatos/efectos adversos , Polisorbatos/química , Polisorbatos/uso terapéutico , Ratas Wistar , Tensoactivos/administración & dosificación , Tensoactivos/efectos adversos , Tensoactivos/química , Tensoactivos/uso terapéutico , Aumento de Peso/efectos de los fármacosRESUMEN
Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.
Asunto(s)
Erupciones por Medicamentos/tratamiento farmacológico , Glicéridos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Hypericum , Radiodermatitis/tratamiento farmacológico , Terpenos/uso terapéutico , Adulto , Anciano , Quimioradioterapia/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Erupciones por Medicamentos/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia/métodos , Radiodermatitis/etiologíaRESUMEN
OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. METHODS: Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. RESULTS: Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. CONCLUSION: Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement.
Asunto(s)
Placa Dental/prevención & control , Gingivitis/prevención & control , Glicéridos/uso terapéutico , Antisépticos Bucales/uso terapéutico , Terpenos/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic antiemetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al., 2015). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually elicited conditioned gaping, and this effect was reversed by coadministration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. Because there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment. (PsycINFO Database Record
Asunto(s)
Ácidos Araquidónicos/metabolismo , Corteza Cerebral/efectos de los fármacos , Endocannabinoides/metabolismo , Glicéridos/metabolismo , Monoacilglicerol Lipasas/efectos de los fármacos , Amidohidrolasas , Animales , Ácidos Araquidónicos/uso terapéutico , Endocannabinoides/uso terapéutico , Glicéridos/uso terapéutico , Cloruro de Litio/farmacología , Modelos Animales , Monoacilglicerol Lipasas/metabolismo , Náusea , Alcamidas Poliinsaturadas , Ratas , Ratas Sprague-Dawley , Serotonina , Vómito Precoz/terapiaRESUMEN
In recent years, a library of approx. 70 N-acyl aminoacids (NAAAs) was discovered in the rat brain. A particular member of this family of compounds is arachidonoyl serine (AraS), which has generated special interest as a potential therapy for traumatic brain injury (TBI). This is due to its structural similarity to the endocannabinoid (eCB) 2-arachidonoyl glycerol (2-AG), which was previously shown to be beneficial in the recovery in a closed head injury model of TBI. Indeed, AraS exerted eCB-mediated neuroprotection, which was evident in numerous aspects related to the secondary damage characterizing TBI. These findings promoted broadening of the research to additional compounds of the NAAA family that share a structural similarity to AraS, namely, palmitoyl serine (PalmS) and oleoyl serine. The latter did not exhibit any improvement in recovery, whereas the former displayed some neuroprotection, albeit inferior to 2-AG and AraS, via unknown mechanisms. Interestingly, when a combined treatment of 2-AG, AraS and PalmS was tested, the overall effect on the severity score was inferior to their individual effects, suggesting not only a lack of direct or indirect synergism, but also possibly some spatial hindrance. Taken together, the complexity of the damage caused by TBI and the many open questions concerning the role of the eCB system in health and disease, the findings so far may serve as a small trace to the understanding of the eCB system, as well as of the mechanisms underlying TBI.
Asunto(s)
Aminoácidos/farmacología , Aminoácidos/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Endocannabinoides/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Animales , Ácidos Araquidónicos/farmacología , Ácidos Araquidónicos/uso terapéutico , Encéfalo/efectos de los fármacos , Endocannabinoides/farmacología , Endocannabinoides/uso terapéutico , Glicéridos/farmacología , Glicéridos/uso terapéutico , HumanosRESUMEN
Parkinson's disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain. Symptomatic therapies are available but no treatment slows or prevents the loss of neurons. Neuroinflammation has been implicated in its pathogenesis. To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients. Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated. The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death. Furthermore, the addition of DFU (25mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects. Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits. The results expand the current understanding of the role that this signalling system has and its potential influence in PD.
Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Ácidos Araquidónicos/uso terapéutico , Endocannabinoides/uso terapéutico , Glicéridos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Neurotoxinas/toxicidad , Enfermedad de Parkinson/dietoterapia , Enfermedad de Parkinson/etiología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Benzodioxoles/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Muerte Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Furanos/uso terapéutico , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Trastornos Neurológicos de la Marcha/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Piperidinas/uso terapéutico , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a 3-week time period. The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in plasma and brain areas involved in the control of these manifestations. Patients with knee osteoarthritis and healthy controls were recruited to evaluate pain, affective, and cognitive symptoms, as well as plasma endocannabinoid levels and cannabinoid receptor gene expression in peripheral blood lymphocytes. The affective manifestations of osteoarthritis were enhanced in CB1R knockout mice and absent in CB2R knockouts. Interestingly, both ACEA and JWH133 ameliorated the nociceptive and affective alterations, whereas ACEA also improved the associated memory impairment. An increase of 2-AG levels in prefrontal cortex and plasma was observed in this mouse model of osteoarthritis. In agreement, an increase of 2-AG plasmatic levels and an upregulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in patients with osteoarthritis compared with healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective, and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.
Asunto(s)
Trastornos del Conocimiento/etiología , Endocannabinoides/metabolismo , Trastornos del Humor/etiología , Osteoartritis/complicaciones , Anciano , Animales , Ácidos Araquidónicos/metabolismo , Ácidos Araquidónicos/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Endocannabinoides/genética , Endocannabinoides/uso terapéutico , Inhibidores Enzimáticos/toxicidad , Femenino , Glicéridos/metabolismo , Glicéridos/uso terapéutico , Humanos , Yodoacetatos/toxicidad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/tratamiento farmacológico , Trastornos del Humor/genética , Osteoartritis/inducido químicamente , Osteoartritis/genética , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Receptor Cannabinoide CB1/deficiencia , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB2/deficiencia , Receptor Cannabinoide CB2/genética , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMEN
The endocannabinoid (eCB) system helps recovery following traumatic brain injury (TBI). Treatment with 2-arachidonoylglycerol (2-AG), a cerebral eCB ligand, was found to ameliorate the secondary damage. Interestingly, the fatty acid amino acid amide (FAAA) N-arachidonoyl-L-serine (AraS) exerts similar eCB dependent neuroprotective. The present study aimed to investigate the effects of the FAAA palmitoyl-serine (PalmS) following TBI. We utilized the TBI model in mice to examine the therapeutic potential of PalmS, injected 1 h following closed head injury (CHI). We followed the functional recovery of the injured mice for 28 days post-CHI, and evaluated cognitive and motor function, lesion volume, cytokines levels, molecular signaling, and infarct volume at different time points after CHI. PalmS treatment led to a significant improvement of the neurobehavioral outcome of the treated mice, compared with vehicle. This effect was attenuated in the presence of eCBR antagonists and in CB2-/- mice, compared to controls. Unexpectedly, treatment with PalmS did not affect edema and lesion volume, TNFα and IL1ß levels, anti-apoptotic mechanisms, nor did it exert improvement in cognitive and motor function. Finally, co-administration of PalmS, AraS and 2-AG, did not enhance the effect of the individual drugs. We suggest that the neuroprotective action of PalmS is mediated by indirect activation of the eCB receptors following TBI. One such mechanism may involve receptor palmitoylation which has been reported to result in structural stabilization of the receptors and to an increase in their activity. Further research is required in order to establish this assumption.
Asunto(s)
Lesiones Encefálicas/prevención & control , Endocannabinoides/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Palmitatos/uso terapéutico , Serina/uso terapéutico , Animales , Ácidos Araquidónicos/farmacología , Ácidos Araquidónicos/uso terapéutico , Lesiones Encefálicas/patología , Relación Dosis-Respuesta a Droga , Endocannabinoides/farmacología , Glicéridos/farmacología , Glicéridos/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fármacos Neuroprotectores/farmacología , Palmitatos/farmacología , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/deficiencia , Serina/farmacologíaRESUMEN
To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28% in the AG-PUFA group and 22% in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2% in the AG-PUFA group and 58.5% in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.
Asunto(s)
Ácidos Grasos Omega-3/uso terapéutico , Hipertrigliceridemia/sangre , Hipertrigliceridemia/dietoterapia , Triglicéridos/sangre , Anciano , Método Doble Ciego , Ésteres/química , Ésteres/uso terapéutico , Ayuno/sangre , Ácidos Grasos Omega-3/química , Femenino , Glicéridos/química , Glicéridos/uso terapéutico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. METHODS: A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. RESULTS: The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. CONCLUSIONS: Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.
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Quimioradioterapia/efectos adversos , Glicéridos/uso terapéutico , Neoplasias de Cabeza y Cuello/radioterapia , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Radiodermatitis/tratamiento farmacológico , Terpenos/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Quimioradioterapia/métodos , Femenino , Flores/química , Humanos , Hypericum/química , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia/efectos adversosRESUMEN
Objetivou-se analisar a comunicação não verbal entre enfermeiros e idosos na consulta de enfermagem à luz do referencial teórico de Hall. Estudo exploratório descritivo com abordagem quantitativa, realizado por filmagens das consultas de enfermagem com idosos em Unidades Básicas de Saúde do município de João Pessoa-Paraíba, analisadas a cada um minuto, totalizando 1.575 interações não verbais. A análise mostra predomínio de enfermeiros (90,63%) e idosos (65,63%) do sexo feminino e classificação regular para a maioria dos fatores com prevalência da postura sentada (80,09%), cadeiras uma em frente a outra (64,46%), distância pessoal (91,40%), expressão facial tranquila (59,78%), uso do toque apenas ao realizar um procedimento técnico (53,33%), interação visual enquanto manipula objetos (57,69%) e volume de voz inalterado (48,79%). Esses resultados refletem a necessidade de os enfermeiros dominarem conscientemente suas manifestações corporais e faciais a fim de melhor interagirem com o idoso.
The aim is to analyze the nonverbal communication between nurses and the elderly in the nursing consultation based on the theory by Hall. The research concerns a descriptive exploratory study and it has a quantitative approach. It took place through filmings of the nursing consultations which happened in Health Basic Units in João Pessoa, Paraíba, Brazil, observed every minute, a total of 1.575 nonverbal interactions. The analysis has showed the predominance of the female nurses (90.63%) and the elderly (65.63) and a regular classification for most of the factors as a prevalence of a sitting set (80.09), opposite chairs (64.46%), personal distance (91.40%), calm facial expression (59.78%), touch was used for a technical procedure (53.33%), visual interaction for the manipulation of the objects (57.69) and no alteration in the voice volume (48.79%). These results reflect the necessity of the nurses to domain consciously their corporal and facial manifestations in order to improve the interaction with the elderly.
El objetivo es analizar la comunicación no verbal entre enfermeros y ancianos en la consulta de enfermería bajo la teoría de Hall. Estudio exploratório descriptivo con abordaje cuantitativa, realizada a través de filmaciones de consultas con ancioanos en Unidades Básicas de Saúde de João Pessoa - Paraíba, totalizando 1.1575 interacciones no verbales. El análisis muestra predomínio de enfermeros (60,63%) y ancianos (65,63%) de sexo femenino y classificación Regular para la mayoría de factores con predominio de postura sentada (80,09%), sillas una frente a otra (64,46%), distancia personal (91,40%), expresión facial tranquila (59,78%), uso de contacto sólo para realizar procedimientos técnicos (53,33%), interacción visual cuando manipula objetos (57,69%) y volumen de voz inalterado (48,79%). Estos resultados reflejan la necessidad de que los enfermeros dominen conscientemente manifestaciones corporales y faciales a fin de mejorar la interacción con el anciano.
Asunto(s)
Humanos , Colelitiasis/terapia , Éteres Metílicos , Ácidos y Sales Biliares/uso terapéutico , Caprilatos , Colelitiasis/tratamiento farmacológico , Colelitiasis/enfermería , Educación Continua en Enfermería , Endoscopía , Éteres/uso terapéutico , Glicéridos/uso terapéutico , Litotricia , Esfinterotomía TransduodenalRESUMEN
Objective: To evaluate whether the application of bilevel positive airway pressure in the postoperative period of bariatric surgery might be more effective in restoring lung volume and capacity and thoracic mobility than the separate application of expiratory and inspiratory positive pressure. Method: Sixty morbidly obese adult subjects who were hospitalized for bariatric surgery and met the predefined inclusion criteria were evaluated. The pulmonary function and thoracic mobility were preoperatively assessed by spirometry and cirtometry and reevaluated on the 1st postoperative day. After preoperative evaluation, the subjects were randomized and allocated into groups: EPAP Group (n=20), IPPB Group (n=20) and BIPAP Group (n=20), then received the corresponding intervention: positive expiratory pressure (EPAP), inspiratory positive pressure breathing (IPPB) or bilevel inspiratory positive airway pressure (BIPAP), in 6 sets of 15 breaths or 30 minutes twice a day in the immediate postoperative period and on the 1st postoperative day, in addition to conventional physical therapy. Results: There was a significant postoperative reduction in spirometric variables (p<0.05), regardless of the technique used, with no significant difference among the techniques (p>0.05). Thoracic mobility was preserved only in group BIPAP (p>0.05), but no significant difference was found in the comparison among groups (p>0.05). Conclusion: The application of positive pressure does not seem to be effective in restoring lung function after bariatric surgery, but the use of bilevel positive pressure can preserve thoracic mobility, although this technique was not superior to the other techniques. .
Objetivo: Avaliar se a aplicação de dois níveis de pressão positiva nas vias aéreas no pós-operatório de cirurgia bariátrica pode ser mais efetiva do que quando aplicadas pressões positivas expiratória e inspiratória separadamente na restauração dos volumes e capacidades pulmonares e na mobilidade torácica. Método: Foram avaliadas 60 voluntárias adultas, obesas mórbidas, internadas para realização da cirurgia bariátrica. Afunção pulmonar e a mobilidade torácica foram avaliadas por meio da espirometria e da cirtometria no pré-operatório e reavaliadas no primeiro pós-operatório. Após a avaliação pré-operatória, as voluntárias foram randomizadas e alocadas nos grupos G EPAP (n=20), G RPPI (n=20) e G BIPAP (n=20) e então receberam a intervenção proposta, pressão positiva expiratória nas vias aéreas (EPAP), respiração por pressão positiva inspiratória (RPPI) ou pressão positiva binível nas vias aéreas (BIPAP), em sessões de seis séries de 15 respirações ou de 30 minutos, duas vezes ao dia no pós-operatório imediato e no primeiro pós-operatório, além do tratamento fisioterapêutico convencional. Resultados: Houve redução significativa das variáveis espirométricas no pós-operatório (p<0,05), independente do recurso utilizado, não havendo diferença significativa entre as técnicas (p>0,05), e preservação da mobilidade torácica somente nas voluntárias do grupo BIPAP (p>0,05), porém sem diferença nas comparações entre os grupos (p>0,05). Conclusão: A aplicação de pressão positiva parece não ser efetiva na restauração da função ...
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Humanos , Colelitiasis/tratamiento farmacológico , Éteres/uso terapéutico , Glicéridos/uso terapéutico , Éteres Metílicos , Caprilatos , Colelitiasis/análisis , Colelitiasis , Colesterol/análisis , Técnicas In Vitro , Tomografía Computarizada por Rayos XRESUMEN
Background: Collaborative actions between family and therapist are essential to the rehabilitation process, and they can be a catalyst mechanism to the positive outcomes in children with cerebral palsy (CP). Objectives: To describe functional priorities established by caregivers of CP children by level of severity and age, and to assess changes on performance and satisfaction on functional priorities reported by caregivers, in 6-month interval. Method: 75 CP children, weekly assisted at Associação Mineira de Reabilitação, on physical and occupational therapy services. The following information was collected: gross motor function (Gross Motor Function Classification System-GMFCS) and functional priorities established by caregivers (Canadian Occupational Performance Measure-COPM). Data were collected in two moments, with a 6-month interval. Results: The main functional demands presented by caregivers were related to self-care activities (48.2%). Parents of children with severe motor impairment (GMFCS V) pointed higher number of demands related to play (p=0.0036), compared to the other severity levels. Parents of younger children reported higher number of demands in mobility (p=0.025) and play (p=0.007), compared to other age groups. After 6 months, there were significant increase on COPM performance (p=0.0001) and satisfaction scores (p=0.0001). Conclusions: Parents of CP children identified functional priorities in similar performance domains, by level of severity and age. Orienting the pediatric rehabilitation process to promote changes in functional priorities indentified by caregivers can contribute to the reinforcement of the parent-therapist collaboration. .
Contextualização: Ações colaborativas entre família e terapeuta são essenciais para o processo de reabilitação, podendo constituir mecanismo catalisador de desfechos funcionais positivos para crianças com paralisia cerebral (PC). Objetivos: Descrever prioridades funcionais identificadas por cuidadores de crianças com PC por nível de gravidade e idade e avaliar mudanças no desempenho e satisfação reportadas pelos cuidadores nas prioridades identificadas no intervalo de seis meses. Método: De 75 crianças com PC, atendidas semanalmente naAssociação Mineira de Reabilitação, nos serviços de fisioterapia e de terapia ocupacional, foram coletadas informações referentes à função motora grossa (Sistema de Classificação da Função Motora Grossa-GMFCS) e às prioridades funcionais estabelecidas pelos cuidadores (Medida Canadense de Desempenho Ocupacional-COPM). Os dados foram coletados em dois períodos, com intervalo de seis meses. Resultados: As principais demandas apontadas pelos cuidadores referiram-se às atividades de cuidados pessoais (48,2%). Pais de crianças com comprometimento motor grave (GMFCS V) apresentaram maior número de demandas relacionadas ao brincar (p=0,036), comparadas com outros níveis de comprometimento. Pais de crianças mais jovens reportaram maior número de demandas em mobilidade (p=0,025) e brincar (p=0,007) em relação aos outros grupos etários. Após seis meses, observou-se aumento significativo dos escores de desempenho (p=0,0001) e de satisfação (p=0,0001) da COPM. Conclusões: Pais de crianças com PC identificaram prioridades funcionais em áreas de desempenho semelhantes por nível de gravidade da função motora grossa e por grupo etário. Direcionar o processo ...
Asunto(s)
Humanos , Colelitiasis/terapia , Solventes/uso terapéutico , Ácidos y Sales Biliares/uso terapéutico , Enfermedades de los Conductos Biliares/terapia , Caprilatos , Catéteres de Permanencia , Colelitiasis/análisis , Éteres/uso terapéutico , Glicéridos/uso terapéuticoRESUMEN
BACKGROUND: The mechanisms underlying breathing exercises have not been fully elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises (diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and intercostal exercise) the on breathing pattern and thoracoabdominal motion in healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23±1.5 years old and with normal pulmonary function tests, participated in the study. The subjects were evaluated using the optoelectronic plethysmography system in a supine position with a trunk inclination of 45° during quiet breathing and the breathing exercises. The order of the breathing exercises was randomized. Statistical analysis was performed by the Friedman test and an ANOVA for repeated measures with one factor (breathing exercises), followed by preplanned contrasts and Bonferroni correction. A p<0.005 value was considered significant. RESULTS: All breathing exercises significantly increased the tidal volume of the chest wall (Vcw) and reduced the respiratory rate (RR) in comparison to quiet breathing. The diaphragmatic breathing exercise was responsible for the lowest Vcw, the lowest contribution of the rib cage, and the highest contribution of the abdomen. The sustained maximal inspiration exercise promoted greater reduction in RR compared to the diaphragmatic and intercostal exercises. Inspiratory sighs and intercostal exercises were responsible for the highest values of minute ventilation. Thoracoabdominal asynchrony variables increased significantly during diaphragmatic breathing. CONCLUSIONS: The results showed that the breathing exercises investigated in this study produced modifications in the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well as in thoracoabdominal motion (e.g., increase in abdominal contribution during diaphragmatic breathing), among others. .
CONTEXTUALIZAÇÃO: Os mecanismos envolvidos na execução dos exercícios respiratórios não foram completamente elucidados. OBJETIVOS: Avaliar o impacto de quatro exercícios respiratórios(diafragmático, suspiros inspiratórios, inspiração máxima sustentada e intercostal) sobre o padrão respiratório e o movimento toracoabdominal em indivíduos saudáveis. MÉTODO: Participaram do estudo15 indivíduos de ambos os sexos (23±1,5 anos com prova de função pulmonar normal). Os indivíduos foram avaliados por meio da pletismografia optoeletrônica na posição supina com inclinação de tronco de 45° durante a respiração tranquila e durante a realização dos exercícios respiratórios. A ordem dos exercícios foi randomizada. Os dados foram analisados pelo teste de Friedman e ANOVA para medidas repetidas com um fator (exercícios respiratórios) seguidos de contrastes pré-planejados e correção de Bonferroni, sendo p<0,005 considerado significativo. RESULTADOS: Todos os exercícios respiratórios promoveram aumento significativo do volume corrente da parede torácica (VCpt) e redução da frequência respiratória (f) quando comparados à respiração tranquila. O exercício diafragmático foi responsável pelo menor VCpt, menor contribuição da caixa torácica e maior contribuição do abdômen. A inspiração máxima sustentada promoveu redução significativamente maior da f comparada aos exercícios diafragmático e intercostal. Os exercícios suspiros inspiratórios e intercostal foram responsáveis pelos maiores valores de ventilação minuto. Os índices de assincronia toracoabdominal aumentaram significativamente ...
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ceruletida/uso terapéutico , Colelitiasis/terapia , Glicéridos/uso terapéutico , Solventes/uso terapéutico , Caprilatos , Colangiografía , Colelitiasis , Evaluación de MedicamentosRESUMEN
BACKGROUND: Shark liver oil (SLO) contains both alkylglycerols (AKG) and squalene and is an ancient remedy among the fishermen on the west coast of Norway and Sweden. Literature reports showed that alkyglycerols enhance Fc-receptor mediated phagocytosis, increase humoral immune response and delay hypersensitivity reactions. METHODS: On this background we performed an open spontaneous study on 40 very old aged surgical patients preoperatively treated with alkyglycerols (500 mg twice a day for 4 weeks), in order to reduce the risks of operation, counteracting the postoperative inflammatory and anergic conditions thus achieving quick and plain recovery. To better understand the possible therapeutic impact of alkyglycerols we compared on a case/control basis treated versus untreated patients submitted contemporarily to the identical operation and exposed to the same environmental and seasonal risks. RESULTS: The onset of complications was reduced in the alkyglycerols treated group and the compliance to the natural treatment was excellent without any serious adverse effect. WBC count and IgG significant increase (respectively p <0.05 and p <0.001) might explain some sort of protection against infectious agents and wound repair adverse events. Also lymphocytes concentration significantly increased in the AKG treated group (p <0.001) whereas a slight decrease was observed in the control group. Conversely neutrophils significantly decreased in the AKG treated group (p <0.001) meaning that patients have no more infections and have re-established their physiologic state. However a significant increase was observed in the control group (p <0.05). CRP significantly decreased in the group receiving AKG (p <0.05), thus evidencing a slight antiinflammtory effect of the product. Also ESR decreased from a baseline in the group receiving AKG. CONCLUSIONS: In conclusion we suggest the opportunity to introduce this nutraceutical product in dosages of 500 mg twice a day to very old people before surgical treatment for an effective modulation of leukocytes and soluble immune reactivity according with the shark liver oil consumption trend in the northern Europe countries folk medicine. For this reason it might be advisable a wider study on a substantially bigger patients cohort focused on the complication rate prevention or control.