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1.
Int J Mol Sci ; 20(16)2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426602

RESUMO

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.


Assuntos
Alanina/análogos & derivados , Anti-Inflamatórios/uso terapêutico , Córnea/efeitos dos fármacos , Síndromes do Olho Seco/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Nervos Periféricos/efeitos dos fármacos , Quinolonas/farmacologia , Alanina/farmacologia , Alanina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Córnea/inervação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Neuroprotetores/uso terapêutico , Quinolonas/uso terapêutico
2.
Biomed Res Int ; 2019: 4750624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317030

RESUMO

Introduction: The aim of this research was to test, in an animal model, the nerve regeneration technique with a hypoallergenic acellular dermal matrix used to wrap the microsurgical neural suture. Materials and Methods: Two groups of rats received the cut of limb right median nerves. The regeneration technique considers for both groups an end-to-end nerve suture. In the experimental group (A) was used also a wrapping protocol by a conduit of collagen matrix currently used in oral surgery. The animals underwent functional grasping tests (at 1, 3, 5, and 7 months) and a histological and quantitative analysis of distal nerve was performed at the end of experimental time. Result: After seven months, the grasping test reveals functional recovery in each tested animal; this improvement is more evident in Group A. The fibers appear well organized with restored myelin sheaths in both groups. Group A showed a great quantity of connective tissue surrounding the nerve. The quantitative morphology analysis in both groups shows a similar fibers density, fiber diameter, and myelin thickness. The differences between the groups in axon mean diameter are significant. In Group A M/d, D/d, and g-ratio is significantly higher compared to control group. Conclusions: Histological and functional assessments show a functional recovery of the injured nerve in the test groups, stressed by the results of the grasping tests and the meaningful increasing in fiber diameter and higher g-ratio. Moreover, a connective tissue cuff distinguishes the distal portion of the injured nerve. Considering the easy availability and handling of the material used in this study we can conclude that this experimental technique can be considered as a valid alternative to protect nerves in nerve wrap surgery.


Assuntos
Nervo Mediano/crescimento & desenvolvimento , Bainha de Mielina/genética , Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Derme Acelular/metabolismo , Animais , Axônios/metabolismo , Modelos Animais de Doenças , Humanos , Nervo Mediano/efeitos dos fármacos , Procedimentos Neurocirúrgicos/métodos , Nervos Periféricos/fisiopatologia , Ratos , Recuperação de Função Fisiológica , Nervo Isquiático/fisiopatologia
3.
Best Pract Res Clin Anaesthesiol ; 33(1): 37-46, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31272652

RESUMO

A perineural catheter with a continuous infusion of local anesthetic is an excellent option for postoperative analgesia; however, its limitations include limited duration of action (i.e., 3-7 days) as well as a risk of infection and dislodgement. Furthermore, these blocks may cause dense sensory and motor blockades that under certain circumstances may not be ideal. There is novel evidence that ultrasound-guided percutaneous peripheral nerve stimulation (pPNS) may serve as an alternative approach free of the limitations associated with peripheral nerve blocks. In this review, we discuss the evidence for pPNS on postoperative acute pain management. Subsequently, we briefly discuss additional alternatives to continuous peripheral nerve blocks, including cryoanalgesia and liposomal bupivacaine.


Assuntos
Cateteres de Demora , Dor Pós-Operatória/diagnóstico por imagem , Dor Pós-Operatória/prevenção & controle , Nervos Periféricos/diagnóstico por imagem , Estimulação Elétrica Nervosa Transcutânea/métodos , Ultrassonografia de Intervenção/métodos , Analgesia/métodos , Analgesia/tendências , Cateteres de Demora/tendências , Humanos , Nervos Periféricos/efeitos dos fármacos , Estimulação Elétrica Nervosa Transcutânea/tendências , Ultrassonografia de Intervenção/tendências
4.
Ideggyogy Sz ; 72(5-6): 159-164, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31241259

RESUMO

Background and purpose: The purpose of this prospective study was to investigate whether mid-term treatment with oral isotretinoin may impact peripheral nerve function. Methods: In this study, we included 28 patients with no apparent neurological or neurophysiological findings. The patients received treatment with oral isotretinoin for papulopustular or nodulocystic acne. The patients with normal findings in the first examination were given 1 mg/kg/day oral isotretinoin. Neurological examinations and electroneurographic studies were performed before and 6 months after the onset of isotretinoin treatment. Results: Clinical examinations and electroneurographic evaluations prior to treatment revealed no abnormalities in any of the patients. However, 20 patients (72%) displayed one or more abnormal values in the tested parameters after treatment. Although the mean amplitudes of compound muscle action potential of the ulnar and median nerves did not vary, significant decreases were observed in the mean sensory conduction velocities of median, ulnar, sural, medial plantar, medial dorsal cutaneous, and dorsal sural nerves 6 months after the onset of treatment. Conclusion: Systemic use of isotretinoin may cause electroneurographic changes. Probable electroneurographic alterations may be detected at a much earlier period via dorsal sural nerve tracing when electrophysiological methods used in routine clinical practice cannot detect these changes.


Assuntos
Acne Vulgar/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Isotretinoína/administração & dosagem , Condução Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervo Sural/efeitos dos fármacos , Administração Oral , Fármacos Dermatológicos/efeitos adversos , Esquema de Medicação , Humanos , Isotretinoína/efeitos adversos , Nervos Periféricos/fisiopatologia , Estudos Prospectivos , Dermatopatias/tratamento farmacológico , Nervo Sural/fisiopatologia
5.
Drug Metab Rev ; 51(3): 266-292, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203666

RESUMO

Currently, there are no established adjuvant drugs for the acceleration of peripheral nerve regeneration. In this paper, we reviewed the literature from the last 10 years and described the drugs proved to accelerate the functional and histological regeneration of the peripheral nerves, either after trauma or in neuropathy experimental models. The vast majority of the studies were experimental with very few small clinical studies, which indicates the need for prospective randomized studies to identify the best drugs to use as adjuvants for nerve regeneration.


Assuntos
Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Humanos , Imunossupressores/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia
6.
Injury ; 50(4): 834-847, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30922661

RESUMO

The use of suture associated with heterologous fibrin sealant has been highlighted for reconstruction after peripheral nerve injury, having the advantage of being safe for clinical use. In this study we compared the use of this sealant associated with reduced number of stitches with conventional suture after ischiatic nerve injury. 36 Wistar rats were divided into 4 groups: Control (C), Denervated (D), ischiatic nerve neurotmesis (6 mm gap); Suture (S), epineural anastomosis after 7 days from neurotmesis, Suture + Fibrin Sealant (SFS), anastomosis with only one suture point associated with Fibrin Sealant. Catwalk, electromyography, ischiatic and tibial nerve, soleus muscle morphological and morphometric analyses were performed. The amplitude and latency values of the Suture and Suture + Fibrin Sealant groups were similar and indicative of nerve regeneration.The ischiatic nerve morphometric analysis in the Suture + Fibrin Sealant showed superior values related to axons and nerve fibers area and diameter when compared to Suture group. In the Suture and Suture + Fibrin Sealant groups, there was an increase in muscle weight and in fast fibers frequency, it was a decrease in the percentage of collagen compared to group Denervated and in the neuromuscular junctions, the synaptic boutons were reestablished.The results suggest a protective effect at the lesion site caused by the fibrin sealant use. The stitches reduction minimizes the trauma caused by the needle and it accelerates the surgical practice. So the heterologous fibrin sealant use in nerve reconstruction should be considered.


Assuntos
Adesivo Tecidual de Fibrina/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Animais , Axônios , Axotomia , Masculino , Modelos Animais , Regeneração Nervosa/fisiologia , Ratos , Ratos Wistar , Procedimentos Cirúrgicos Reconstrutivos , Suturas
7.
Reg Anesth Pain Med ; 44(1): 46-51, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640652

RESUMO

BACKGROUND AND OBJECTIVES: This multicenter, randomized trial compared 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular brachial plexus block. Our research hypothesis was that all three doses of dexamethasone would result in equivalent durations of motor block (equivalence margin=3.0 hours). METHODS: Three hundred and sixty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block were randomly allocated to receive 2, 5, or 8 mg of preservative-free perineural dexamethasone. The local anesthetic agent (35 mL of lidocaine 1%-bupivacaine 0.25% with epinephrine 5 µg/mL) was identical in all subjects. Patients and operators were blinded to the dose of dexamethasone. During the performance of the block, the performance time, number of needle passes, procedural pain, and complications (vascular puncture, paresthesia) were recorded. Subsequently a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min), onset time as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids, or general anesthesia). Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block, and postoperative analgesia. The main outcome variable was the duration of motor block. RESULTS: No intergroup differences were observed in terms of technical execution (performance time/number of needle passes/procedural pain complications), onset time, success rate, and surgical anesthesia. Furthermore, all three doses of dexamethasone provided similar durations of motor block (14.9-16.1 hours) and sensory block. Although 5 mg provided a longer analgesic duration than 2 mg, the difference (2.7 hours) fell within our pre-established equivalence margin (3.0 hours). CONCLUSIONS: 2, 5, and 8 mg of dexamethasone provide clinically equivalent sensorimotor and analgesic durations for ultrasound-guided infraclavicular block. Further trials are required to compare low (ie, 2 mg) and ultra-low (eg, 0.5-1 mg) doses of perineural dexamethasone for brachial plexus blocks. TRIAL REGISTRATION NUMBER: TCTR20150624001.


Assuntos
Bloqueio do Plexo Braquial/métodos , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Ultrassonografia de Intervenção/métodos , Adulto , Clavícula/diagnóstico por imagem , Clavícula/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/efeitos dos fármacos
8.
J Toxicol Environ Health A ; 82(2): 99-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30652531

RESUMO

Iron (Fe) deficiency (FeD) and manganese (Mn) overexposure (MnOE) may result in several neurological alterations in the nervous system. Iron deficiency produces unique neurological deficits due to its elemental role in central nervous system (CNS) development and myelination, which might persist after normalization of Fe in the diet. Conversely, MnOE is associated with diverse neurocognitive deficits. Despite these well-known neurotoxic effects on the CNS, the influence of FeD and MnOE on the peripheral nervous system (PNS) remains poorly understood. The aim of the present investigation was to examine the effects of developmental FeD and MnOE or their combination on the sciatic nerve of young and adult rats. The parameters measured included divalent metal transporter 1 (DMT1), transferrin receptor (TfR), myelin basic protein (MBP) and peripheral myelin protein 22 (PMP22) expression, as well as Fe levels in the nerve. Our results showed that FeD produced a significant reduction in MBP and PMP22 content at P29, which persisted at P60 after Fe-sufficient diet replenishment regardless of Mn exposure levels. At P60 MnOE significantly increased sciatic nerve Fe content and DMT1 expression. However, the combination of FeD and MnOE produced no marked motor skill impairment. Evidence indicates that FeD appears to hinder developmental peripheral myelination, while MnOE may directly alter Fe homeostasis. Further studies are required to elucidate the interplay between these pathological conditions.


Assuntos
Expressão Gênica/efeitos dos fármacos , Ferro/deficiência , Manganês/efeitos adversos , Atividade Motora/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Fatores Etários , Animais , Masculino , Nervos Periféricos/química , Ratos , Ratos Sprague-Dawley
9.
Eur J Anaesthesiol ; 36(1): 40-47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308523

RESUMO

BACKGROUND: Cleft defects are common craniofacial malformations which require early surgical repair. These patients are at high risk of postoperative airway obstruction and respiratory failure. Cleft surgery may require high doses of opioids which may contribute to these complications. OBJECTIVES: To compare the effectiveness of proximal and distal approaches to blocking the maxillary nerve in patients undergoing cleft lip or cleft palate surgery. DESIGN: Randomised, controlled and double-blind study. SETTING: The current study was carried out in Guwahati (Assam, India) between April 2014 and June 2014. PATIENTS: A total of 114 patients older than 6 months who underwent cleft lip or cleft palate surgery were included. Exclusion criteria included coagulation disorders, peripheral neuropathy or chronic pain syndrome, infection in the puncture site, allergy to local anaesthetics, lack of consent and language problems or other barriers that could impede the assessment of postoperative pain. INTERVENTIONS: Patients were randomly assigned to one of two groups: proximal group (bilateral suprazygomatic maxillary nerve blocks) and distal group (bilateral infraorbital nerve blocks for cleft lip repair and bilateral greater and lesser palatine nerve blocks and nasopalatine nerve block for cleft palate surgery). MAIN OUTCOME MEASURE: The primary endpoint was the percentage of patients requiring extra doses of opioids. Secondary endpoints included pain scores, respiratory and nerve block-related complications during the first 24 h. RESULTS: In the intra-operative period, there was a significant reduction of nalbuphine consumption in the proximal group (9.1 vs. 25.4%, P = 0.02). The percentage of patients requiring intra-operative fentanyl was lower in the proximal group (16.4 vs. 30.5%, P = 0.07). There were no differences in either postoperative pain scores or in postoperative complications. No technical failure or block-related complications were reported. CONCLUSION: Bilateral suprazygomatic maxillary nerve block is an effective and safe alternative to the traditional peripheral nerve blocks for cleft lip and cleft palate surgery, in a mixed paediatric and adult population.


Assuntos
Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Bloqueio Nervoso/métodos , Nervos Periféricos/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Epinefrina/uso terapêutico , Feminino , Humanos , Índia , Lactente , Masculino , Nervo Maxilar/efeitos dos fármacos , Palato/inervação
10.
J Surg Res ; 233: 36-40, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502271

RESUMO

BACKGROUND: Restoring function after nerve injury remains one of medicine's greatest challenges. The current approach of epineurial coaptation does not address the fundamental insult at the molecular level: a discontinuity in the axonal membranes. Membrane fusion is possible through agents collectively called chemical fusogens, which are heterogeneous in structure and mechanism of action. We sought a unifying system for classifying fusogens to better understand their role in cell fusion. MATERIALS AND METHODS: We conducted a comprehensive literature review to identify the most commonly cited chemical fusogens, their structures, mechanisms of actions, and clinical applications to date. We identified seven chemical fusogens (polyethylene glycol, chitosan, dextran sulfate, n-nonyl bromide, calcium, sodium nitrate, and H-α-7), which have each been studied to different extents in protoplasts, animals, and humans. RESULTS: Chemical fusogens achieve cell fusion by one of two ways: bringing cells in close enough proximity to each other so the inherent fluidity of the phospholipid membrane allows for their rearrangement or modifying the surface charges of the membranes to diminish repellent charges. Sowers initially put forth a classification system that identified these agents as cell aggregators and membrane modifiers, respectively. We adapted this classification system in the setting of axonal membrane fusion and hypothesized that the most effective approach to axonal membrane repair is likely combination of both. CONCLUSIONS: Chemical fusogens could be grouped into two mechanistic categories-cell aggregators and membrane modifiers. For axonal membrane fusion, a combination of both mechanisms can significantly contribute to advancing outcomes in peripheral nerve repair via a chemical-surgical intervention.


Assuntos
Axônios/efeitos dos fármacos , Fusão de Membrana/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervos Periféricos/efeitos dos fármacos , Animais , Axônios/fisiologia , Cálcio/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Quitosana/farmacologia , Sulfato de Dextrana/farmacologia , Humanos , Hidrocarbonetos Bromados/farmacologia , Nitratos/farmacologia , Nervos Periféricos/citologia , Polietilenoglicóis/farmacologia , Protoplastos/efeitos dos fármacos
11.
Inflammopharmacology ; 27(4): 761-772, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29938333

RESUMO

The study comprises exploring the effects of saponins from Tribulus terrestris (TT) in attenuating the neuropathic pain caused by vincristine (100 µg/ml i.p.) for 10 days (in two 5 day cycles with 2 days pause). Mechanical hyperalgesia and allodynia were assessed by Randall-Sellitto and electronic von Frey tests, respectively. Chemical- induced nociception was assessed by formalin test. Neurophysiological effect of the extract was evaluated by recording sciatic functional index (SFI) on the test days (7, 10, 14, and 21) and sciatic nerve conduction velocity test (SNCV) on the last day. Inflammatory mediators (TNF-α, IL-1ß, and IL-6) in both sciatic nerve and brain and brain neurotransmitters, glutamate and aspartate, were measured to support the behavioral response. The saponins of TT-treated group were found to be effective in the behavioral experiments, implying its activity both centrally and peripherally in attenuating pain. The inflammatory mediators in both sciatic nerve and brain (TNF-α, IL-1ß, and IL-6) were found to be attenuated with TT saponin treatment in comparison to vincristine-treated group, indicating its anti-inflammatory property. The excitatory neurotransmitters, L-glutamic acid and L-aspartic acid, were also found to be attenuated with TT saponins, implying restoration of neuronal damage and synaptic activity caused by high amount of glutamate due to excess TNF-α in brain and reversing the nociceptive threshold lowered due to aspartate. Thus, TT(S) is peripherally and centrally active in lowering the inflammatory mediators, reversing the neuronal damage and increasing the nociceptive threshold caused due to peripheral neuropathy.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Neuralgia/tratamento farmacológico , Nervos Periféricos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Tribulus/química , Animais , Anti-Inflamatórios/farmacologia , Sistema Nervoso Central/metabolismo , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Neurotransmissores/metabolismo , Medição da Dor/métodos , Nervos Periféricos/metabolismo , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Vincristina/farmacologia
12.
Toxicol Appl Pharmacol ; 365: 41-50, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30592963

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancer patients treated with oxalipatin based chemotherapy. AIM: The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatin neurotoxicity in colorectal cancer patients with emphasis on the redox (Nrf-2, MDA), inflammatory (NF-κB, TNF-α), and apoptotic (caspase-3) parameters. METHODS: In this pilot study, 65 patients were recruited using a prospective randomized controlled study design and enrolled randomly into two arms; Arm A, 31 patients received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B, 34 patients received FOLFOX-6 regimen and daily oral L-carnosine (500 mg) along the treatment period. Patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC version 4). RESULTS: The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal. In arm B, the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%) and TNF-α (36.6%); this anti-inflammatory effect entailed also its anti-oxidative and anti-apoptotic effects, thus MDA level (51.8%) and caspase-3 activity (49%) were also reduced, whereas Nrf-2 was increased (38.7%) as compared to Arm A. In both arms a significant correlation was only evident between TNF-α and the neuropathy grading score (P < .03); the correlation analysis was significantly positive between NF-κB and both Nrf-2 and caspase 3. CONCLUSION: L-Carnosine exerted a neuroprotective effect against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients by targeting Nrf-2 and NF-κB pathways.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carnosina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina/uso terapêutico , Nervos Periféricos/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/prevenção & controle , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Carnosina/efeitos adversos , Caspase 3/metabolismo , Egito , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/efeitos adversos , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Projetos Piloto , Estudos Prospectivos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
14.
PLoS One ; 13(12): e0208938, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30533035

RESUMO

In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Transtornos de Deglutição/tratamento farmacológico , Nervos Laríngeos/crescimento & desenvolvimento , Regeneração Nervosa/efeitos dos fármacos , Animais , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/genética , Criança , Deglutição/efeitos dos fármacos , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/crescimento & desenvolvimento , Modelos Animais de Doenças , Feminino , Humanos , Nervos Laríngeos/efeitos dos fármacos , Nervos Laríngeos/patologia , Macrófagos/efeitos dos fármacos , Masculino , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/crescimento & desenvolvimento , Ratos , Regeneração , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Dente Decíduo/citologia , Dente Decíduo/efeitos dos fármacos
15.
Nanomedicine (Lond) ; 13(23): 3009-3023, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30507340

RESUMO

AIM: Procaine that is able to reach the peripheral nervous system (PNS) was conjugated as a ligand with lipid nanovesicle and loaded with ribavirin (a broad spectrum antiviral drug incapable of entering the PNS on its own) to target the PNS with a dual-drug effect. MATERIALS & METHODS: Different physicochemical characterizations, Î³-scintigraphy and electromyography of the developed nanovesicle were conducted. RESULTS: Marked capability of the optimized radiolabeled formulation to target PNS was observed in rats. Electromyography signals were reduced after treatment with the formulation on conscious rats. CONCLUSION: The developed nanocarrier can deliver drug successfully at the PNS and reduce excitation of the nerve and thus give a better therapeutic option for treatment of various diseases and disorders of the PNS.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Nervos Periféricos/efeitos dos fármacos , Procaína/farmacologia , Ribavirina/farmacologia , Anestésicos Locais/farmacologia , Animais , Antivirais/farmacologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Quimioterapia Combinada/métodos , Etanolaminas/química , Lipídeos/química , Masculino , Tamanho da Partícula , Ratos Sprague-Dawley , Propriedades de Superfície , Distribuição Tecidual
16.
Food Funct ; 9(12): 6287-6297, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30411095

RESUMO

SCOPE: Maltol (3-hydroxy-2-methy-4-pyrone), a potent antioxidative agent, typically is used to enhance flavor and preserve food. This study evaluated its effects on preventing diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats and explored its mechanisms. METHODS AND RESULTS: We intraperitoneally injected Sprague-Dawley (SD) rats with STZ (65 mg kg-1, ip) and treated the rats with different doses of maltol after 4 weeks of injection. During treatment, we evaluated motor nerve conduction velocity (MNCV) and thermal and mechanical hyperalgesia and assayed the oxidative stress, Na+-K+-ATPase activity, and apoptosis. Repeated treatment with maltol for 12 weeks significantly improved thermal and mechanical hyperalgesia, increased the MNCV, elevated the Na+-K+-ATPase activity, and ameliorated oxidative stress and apoptosis in STZ-induced diabetic rats. We coincubated RSC96 cells, a Schwann cell line, with maltol and hydrogen peroxide (H2O2, 0.6 mM). Evidently, maltol increased cell viability and inhibited apoptosis after injury by H2O2. CONCLUSIONS: Maltol was demonstrated to prevent DPN development and may provide a new alternative for the treatment of DPN.


Assuntos
Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/tratamento farmacológico , Aromatizantes/administração & dosagem , Pironas/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiopatologia , Ratos , Estreptozocina
17.
J Cancer Res Ther ; 14(5): 1010-1013, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197340

RESUMO

Introduction: Oxaliplatin-induced neurotoxicity is the single main dose-limiting factor in the treatment of colorectal cancer. The degree of neurotoxicity may be either acute and reversible or observed as cumulative and chronic peripheral nerve damage leading to peripheral neuropathy (PNP), walking difficulties, extremity hypersensitivity, tingling and numbness, and increased pain sensation. Aim: The aim of this paper is to determine and compare the ratio of clinical versus subclinical PNP cases in colorectal patients who underwent oxaliplatin treatment. Materials and Methods: Thirty-two colorectal cancer patients were enrolled in the study. Patients received chemotherapy either as folinic acid and 5-fluorouracil and oxaliplatin or capecitabine and oxaliplatin regimen. Electroneurophysiological tests were performed before the treatment and after the 4th cycle when the risk of peripheral nerve damage increases. All patients were subject to a standard neurological examination and a semi-structured questionnaire interview. Results and Discussion: Following oxaliplatin treatment, 21 (66.6%) of all patients presented neurological symptoms and/or electrophysiologically measured signs of PNP; of those, 7 patients (33.4%) displayed only electrophysiological changes and the remaining 14 patients (66.6%) presented fully symptomatic PNP - 4 patients were new neuropathy cases while the other 10 patients were previously diagnosed with PNP and showed signs of further neuronal deterioration and progressing sensory and motor dysfunction. Conclusion: Our study lays ground for further larger scale longitudinal studies on oxaliplatin neurotoxicity and its prevention. We believe that early diagnosis of oxaliplatin-induced neurotoxicity is essential in the prevention of irreversible nerve damage and should be prioritized when assessing and evaluating treatment so that adequate adjustment may be made.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Síndromes Neurotóxicas/patologia , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/patologia , Adulto , Idoso , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neurônios/efeitos dos fármacos , Neurônios/patologia , Síndromes Neurotóxicas/complicações , Síndromes Neurotóxicas/epidemiologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/epidemiologia , Polônia/epidemiologia , Inquéritos e Questionários
18.
Aging Cell ; 17(6): e12833, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30168637

RESUMO

The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti-inflammatory therapies aiming to improve nerve regeneration in old age.


Assuntos
Envelhecimento/patologia , Inflamação/patologia , Regeneração Nervosa , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Quimiocina CCL11/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Compressão Nervosa , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Células de Schwann/patologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia
19.
Int J Biol Macromol ; 119: 1195-1203, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30110602

RESUMO

Schwann cell (SC) is the primary structural and functional part of the peripheral nervous system, and it plays a key role in the repair and regeneration of peripheral nerve. In order to develop a suitable scaffold for SC nerve tissue engineering, three kinds of scaffolds, including pristine collagen, pure oxidized regenerated cellulose-Ca (ORCCa) and collagen/ORC-Ca composite scaffolds, have been fabricated for carrying SC in this study. SC is then seeded on the scaffolds to form SC-scaffold nerve tissue engineering composites and evaluate their biocompatibility. The chemical and physical structure of the scaffolds are investigated by FTIR, NMR and SEM. The wettability of the collagen/ORC-Ca composite scaffold is close to that of pristine collagen, and the tensile strength of the composite scaffold (0.58 MPa) is better than that of pristine collagen (0.36 MPa). Cytotoxicity, cell proliferation, cell adhesion and western blotting assays are conducted to evaluate the biocompatibility and properties of different scaffolds. The results show that the three scaffolds exhibit no toxicity, and the proliferation rate of SC on the collagen/ORC-Ca composite scaffold is significantly higher than that of the other scaffolds (p < 0.05). The number of the adhesion cells on the composite scaffold (244.67 ±â€¯13.02) is much more than that in the pure ORC-Ca group (p < 0.01). Furthermore, the expression of N-Cadheri and PMP22 proteins in the collagen/ORC-Ca composite scaffold is significantly superior to the other two scaffolds (both p < 0.01). Therefore, it could be concluded that the collagen/ORC-Ca composite is a promising candidate as a scaffold for carrying SC to form nerve tissue engineering composites in order to assist the peripheral nervous in the repair and regeneration.


Assuntos
Materiais Biocompatíveis/química , Cálcio/química , Celulose Oxidada/química , Colágeno/química , Portadores de Fármacos/química , Células de Schwann/citologia , Materiais Biocompatíveis/farmacologia , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Celulose Oxidada/farmacologia , Portadores de Fármacos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Teste de Materiais , Fenômenos Mecânicos , Proteínas da Mielina/metabolismo , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiologia , Regeneração , Células de Schwann/química , Molhabilidade
20.
Eur J Anaesthesiol ; 35(10): 745-758, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30095549

RESUMO

BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia. OBJECTIVES: The aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX. DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach. DATA SOURCES: The databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included. RESULTS: A total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P = 0.002; I = 65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P = 0.08; I = 0%). CONCLUSION: This meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5 h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX. TRIAL REGISTRATION: CRD42016042486.


Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Nervos Periféricos/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Dexmedetomidina/efeitos adversos , Quimioterapia Combinada , Humanos , Hipnóticos e Sedativos/efeitos adversos , Nervos Periféricos/fisiologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Resultado do Tratamento
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