Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.308
Filtrar
1.
Anticancer Res ; 39(9): 4721-4728, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519571

RESUMO

BACKGROUND/AIM: Recent research has identified the transcription factors NFATc2 and Sp1 as key regulators in the carcinogenesis of pancreatic carcinoma. This study aimed to examine the effect of clinically achievable dosages of analgesics including ketamine, s-ketamine, metamizole, and paracetamol as well as that of sufentanil, ropicavaine, and lidocaine on pancreatic carcinoma cells and the expression of NFATc2 and Sp1. MATERIALS AND METHODS: The effects of analgesics on the expression of NFATc2 and Sp1 were investigated with immunoblotting. Cell proliferation was measured with the ELISA BrdU assay. RESULTS: In PaTu8988t pancreatic carcinoma cells, 48 h stimulation with ketamine and s-ketamine significantly inhibited proliferation and decreased expression of NFATc2 in the nucleus. The addition of metamizole and lidocaine reduced proliferation of PaTu8988t cells after 48 h. CONCLUSION: New treatment concepts target specific signaling and transcription pathways. The extent to which drugs influence these mechanisms in pancreatic carcinoma cells needs to be investigated in future studies.


Assuntos
Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fator de Transcrição Sp1/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/patologia , Transcrição Genética
2.
Anaesthesia ; 74(11): 1397-1405, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31465115

RESUMO

We performed a randomised, blinded, controlled study with adult patients scheduled for primary total knee arthroplasty under spinal anaesthesia. The aim was to investigate the analgesic effects of adductor canal block using catheter-based repeated boluses, either through a new suture-method catheter or a standard perineural catheter, compared with a single-injection technique. All patients received an adductor canal block after surgery with an initial bolus of 20 ml ropivacaine 0.75%, followed by 20 ml of ropivacaine 0.2% every 8 h in the standard and suture-method catheter groups, and sham boluses for the single-injection group. The primary outcome measure was total opioid consumption (intravenous morphine equivalents) from the end of surgery until 12:00 on postoperative day 2. Secondary outcomes were pain, muscle strength and ambulation. We randomly assigned (1:1:1) and analysed 153 patients. Total opioid consumption was median (IQR [range]) 24 (11-37 [0-148]) mg in the suture-method group, 38 (17-51 [0-123]) mg in the standard catheter group and 37 (14-57 [0-158]) mg in the single-injection group (p = 0.049). Differences were not statistically significant after Bonferroni correction (α = 0.05/3). There were no differences between groups on postoperative day 1. On postoperative day 2, there were no differences between catheter groups, but muscle strength and ambulation were improved compared with the single-injection group. We conclude that providing repeated boluses via a catheter did not decrease opioid consumption or pain compared with a single injection, but improved muscle strength and ambulation on postoperative day 2. The two types of catheters were similar.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio Nervoso/instrumentação , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Ropivacaina/farmacologia , Idoso , Analgesia/métodos , Anestésicos Locais/administração & dosagem , Artroplastia do Joelho , Cateteres , Feminino , Humanos , Injeções , Masculino , Ropivacaina/administração & dosagem , Método Simples-Cego , Suturas , Resultado do Tratamento
3.
Urology ; 133: 72-77, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465791

RESUMO

OBJECTIVE: To assess whether intraurethral anesthesia decreased voiding efficiency (VE), reduced catheterization pain, and impacted urodynamic parameters in healthy adult females. METHODS: In a randomized, double-blind, placebo-controlled trial, participants received two 5 mL doses of either intraurethral aqueous gel or 4% lidocaine gel. The primary outcome was VE during randomized condition uroflow, defined as voided volume/(voided volume + residual volume). The secondary outcomes were pain during catheterization and to confirm previously reported pressure-flow changes. A sample size of 10 per group was planned to detect a clinically significant decrease in VE with a power (1-ß) of 0.99. RESULTS: From October to December 2018, 23 women were screened and 18 were randomized to receive placebo (n = 10) or lidocaine (n = 8). Baseline uroflow VE was similar between the placebo and lidocaine groups (88 ± 6.6% vs 91 ± 5.8%, P = .33). After study drug administration, the changes in VE (post-pre) were similar between placebo and lidocaine groups (-5.4 ± 14% vs 1.7 ± 6.4%, P = .21). Visual analog scores were similar following catheterizations (26.7 ± 12.8 mm vs 36.9 ± 26.8 mm, P = .34). The lidocaine group exhibited lower average flow rates per voided volume (0.04 ± 0.02 s-1 vs 0.02 ± 0.01 s-1, P = .04). CONCLUSION: Intraurethral administration of 4% lidocaine did not decrease VE compared to placebo and did not change pain scores following catheterization. In the lidocaine group, the average flow rate per voided volume was lower. The decrease in flow rate after local anesthesia to the urethra may indicate that urethral sensory feedback contributes to voiding in human micturition.


Assuntos
Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem , Dor/prevenção & controle , Cateterismo Urinário , Micção/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Administração Tópica , Adulto , Anestésicos Locais/farmacologia , Método Duplo-Cego , Feminino , Humanos , Lidocaína/farmacologia , Uretra , Cateterismo Urinário/efeitos adversos
4.
Anaesthesia ; 74(11): 1389-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389614

RESUMO

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio do Plexo Braquial/métodos , Epinefrina/farmacologia , Hemodinâmica/efeitos dos fármacos , Lidocaína/farmacologia , Microcirculação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Hemodinâmica/fisiologia , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Ultrassonografia de Intervenção/métodos , Adulto Jovem
5.
Br J Anaesth ; 123(3): 335-349, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31303268

RESUMO

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Dor Crônica/tratamento farmacológico , Lidocaína/farmacologia , Terapia de Alvo Molecular/métodos , Dor Aguda/metabolismo , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/metabolismo , Humanos , Canais Iônicos/efeitos dos fármacos , Lidocaína/uso terapêutico , Transmissão Sináptica/efeitos dos fármacos
6.
Biol Res ; 52(1): 36, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300048

RESUMO

BACKGROUND: Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells. METHODS: In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine. RESULTS: Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3. CONCLUSIONS: Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.


Assuntos
Anestésicos Locais/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Neoplasias Hepáticas/patologia , Ropivacaina/farmacologia , Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/metabolismo , Microscopia Confocal , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
7.
Eur J Pharmacol ; 860: 172544, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31319069

RESUMO

Brompheniramine as an antihistamine blocked sodium channels, and local anesthetics by blocking sodium channels produced the local anesthetic effects. The authors aimed to assess local anesthetic quality and duration of brompheniramine when compared to the local anesthetic mepivacaine. After rats were shaved and injected subcutaneously on the dorsal skin, the panniculus reflex, induced via applying a noxious pinprick to the skin (injected area), was scored. The dose-response curve and nociceptive block duration of brompheniramine were constructed and compared with mepivacaine. The cutaneous analgesic effects in both brompheniramine and mepivacaine groups were concentration-dependent. On the basis of the amount required to produce a 50% block effect (ED50, 50% effective dose), the drug's potency was brompheniramine (0.89 [0.82-0.96] µmol) better than mepivacaine (2.45 [2.17-2.76] µmol) (P < 0.01). Full recovery time of brompheniramine was more prolonged than mepivacaine's (P < 0.01) on infiltrative cutaneous analgesia when comparing ED25s, ED50s and ED75s. Our preclinical data demonstrated that subcutaneous brompheniramine induces dose-relatedly analgesic effects, and brompheniramine induces prolonged analgesic duration when compared with mepivacaine. Brompheniramine also provokes better cutaneous analgesia than mepivacaine.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Bromofeniramina/administração & dosagem , Bromofeniramina/farmacologia , Administração Cutânea , Animais , Relação Dose-Resposta a Droga , Masculino , Mepivacaína/administração & dosagem , Mepivacaína/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
8.
Biomed Pharmacother ; 117: 109057, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203133

RESUMO

Local anesthetics (LAs) are drugs that promote the reversible blocking of neural transmission by inhibiting the excitation conduction process in peripheral nerves. Tetracaine (TTC) is one of the most common topical anesthetics used in general practice and was applied to provide long-term anesthesia. In this research, poly(L-lactide) nanoparticles (PLA NPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were utilized to construct TTC loaded nanosystems. The mean sizes, drug loading efficiency, cytotoxicity, skin permeation ability, and anesthetic analgesic effect were evaluated and compared in vitro and in vivo. The average particle sizes of blank PLA NPs, SLNs, and NLCs were 93.2, 100.9 and 110.4 nm, respectively. At all the concentrations, PLA NPs, SLNs, and NLCs showed a moderate effect on cell viability. TTC NLCs exhibited the most prominent in vivo efficiency in improving the skin permeation, analgesic time and pain control intensity. Other experiments proved that TTC PLA NPs showed advantages in serum stability and TTC SLNs illustrated the best in vitro permeation efficiency. These three kinds of nano-systems had their own superiority in some respects. Conclusion could be made that in this study, TTC NLCs is the promising system for the long-term anesthesia.


Assuntos
Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Polímeros/química , Tetracaína/química , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Pressão , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos
9.
Int Wound J ; 16(4): 1029-1033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148374

RESUMO

After the introduction of cocaine to the medical practice, local anaesthetics (LA) became essential in pain control. LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. This study aimed to compare the antimicrobial effects of the topical antimicrobial agent mupirocine with those of the LA lidocaine and the combination of lidocaine and adrenalin. In our study, the in vitro antimicrobial effects of 1 mL sterile saline, 20 mg/mL mupirocine, 20 mg/mL Lidocaine, and 20 mg/mL Lidocaine and Adrenaline were tested against Staphylococcus aureus American type culture collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922 as Group C (Control), Group M (Mupirocine), Group L (Lidocaine), and Group LA (Lidocaine + adrenaline), respectively. S aureus ATCC 29213, P aeruginosa ATCC 27853, and E coli ATCC 25922 were cultured onto Mueller-Hinton agar (Oxoid, UK) plates for 18 to 24 hours at 37°C. Colonies from these plates were suspended in sterile saline and a 0.5 McFarland turbidity standard suspension (corresponding to 1.5 × 108 CFU/mL) of each isolate was prepared. S Aureus ATCC 29213 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared with the group C (P ˂ 0.05). P aeruginosa ATCC 27853 inhibition zone diameter values of Group M and Group LA were significantly higher compared with the group C (P ˂ 0.05). E coli ATCC 25922 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared to the group C (P ˂ 0.05). LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. Considering that LAs show antimicrobial effects besides their analgesic effects, they may contribute to preventing the development and reducing the rate of surgical infections, decreasing the requirement to administer antibiotics. However, caution should be exercised not to antagonise the effective treatment of surgical infections, remembering that controversy on the antimicrobial effects of LAs remains in the literature. Therefore, further comprehensive studies with larger patient populations are warranted to demonstrate the antimicrobial effects of LAs.


Assuntos
Anestésicos Locais/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Lidocaína/farmacologia , Mupirocina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Anestésicos Locais/uso terapêutico , Antibacterianos/uso terapêutico , Humanos , Lidocaína/uso terapêutico , Mupirocina/uso terapêutico
10.
Life Sci ; 232: 116606, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254586

RESUMO

AIMS: Bupivacaine, a common local anesthetic, can cause neurotoxicity and abnormal neuro-disorders. However, the precise underlying mechanisms have not been fully elucidated. In this study, we investigated the function of lncRNA MALAT1 in the bupivacaine-induced neurotoxicity process. MATERIALS AND METHODS: SH-SY5Y cells and neonatal mouse DRG neurons were cultured in vitro and treated with bupivacaine to establish a neurotoxicity model. Caspase3 activity and cell survival rates were detected to evaluate the function of lncRNA MALAT1. Western blotting was used to detect the expression levels of PDCD4 and cleaved-caspase-3. A dual-luciferase reporter assay was used to explore the potential binding target of lncRNA MALAT1. RESULTS: We found that the expression of lncRNA MALAT1 was upregulated upon exposure to bupivacaine. Knockdown of lncRNA MALAT1 significantly increased the cell death rates, and Caspase3 activity assays revealed that the apoptosis rates were manifestly increased in the MALAT1 downregulation group. In addition, we screened the possible target and found that miR-101-3p is the direct target of MALAT1 using a dual-luciferase reporter assay; these results suggest that lncRNA MALAT1 may function as a decoy to sponge miR-101-3p. Furthermore, we demonstrated that activation of the MALAT1/miR-101-3p/PDCD4 axis protected cells against bupivacaine treatment. CONCLUSION: We elucidated the function and mechanism of MALAT1 in bupivacaine-induced neurotoxicity. Targeting MALAT1 might provide new methods to prevent neurotoxicity.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Bupivacaína/toxicidade , MicroRNAs/metabolismo , Síndromes Neurotóxicas/etiologia , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Anestésicos Locais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Gânglios Espinais/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , MicroRNAs/genética , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Regulação para Cima/efeitos dos fármacos
11.
Int J Nanomedicine ; 14: 4007-4016, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213812

RESUMO

Background: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films. Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.


Assuntos
Adesivos/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Nanofibras/química , Dor/tratamento farmacológico , Ferida Cirúrgica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adesivos/farmacologia , Anestésicos Locais/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fator de Crescimento Epidérmico/farmacologia , Humanos , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Masculino , Nanofibras/ultraestrutura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Ferida Cirúrgica/patologia
12.
Artigo em Alemão | MEDLINE | ID: mdl-31212342

RESUMO

OBJECTIVE: Comparison of the effectiveness of local anaesthesia (LA) in piglet castration with the combination of scrotal and inguinal application of procaine 2 % and lidocaine 5 % to the intratesticular application of lidocaine 1 % using following parameters: adrenaline (A), noradrenaline (NA), defensive movements and coordinated movement patterns. MATERIAL AND METHODS: In 2 substudies 232 male suckling piglets (3-6 days of age) were randomly allocated to study groups. In groups L5 and group P2 lidocaine 5 % and procaine 2 % was applied inguinally and scrotally, respectively, while piglets of groups H (handling) and K (castration without local anaesthesia) were only fixated as for an injection. In group L1 lidocaine 1 % was injected intratesticularly. After 30 min piglets were were castrated, whereas animals of group H were again only fixated. In substudy 1 (n = 112) blood samples were taken to determine the concentration of catecholamines after castration. During injection and castration defensive movements were judged. In substudy 2 (n = 120) piglets completed a chute to document the individual stress level. RESULTS: Groups H and L1 demonstrated significantly less defensive movements during fixation for injection/injection compared to the other study groups (p ≤ 0.05). After the injection piglets of group P2 had significantly more difficulties in the chute and needed > 50 % more time to complete the course. In all study groups defensive movements during castration were the highest at the moment of severing the spermal cord. Group K obtained the highest possible rating of 8 and differed significantly from the other groups as well as when cutting the skin (p ≤ 0.05). Both the concentration of A and NA significantly rose in all groups. The increase in A and NA was significantly higher in group 2, as well as the increase in NA in group K, both in comparison to the other study groups (p ≤ 0.05). CONCLUSION: None of the applied techniques for local anaesthesia achieved a complete elimination of pain during castration of suckling piglets. The behaviour analysis indicated an altogether higher distress for P2. After castration, this injection led to a neuroendocrine pain reaction that was comparable to or higher than that of group K. In both lidocaine groups (L1, L5) the pain reaction after castration tended to be lower. These results provide approaches to apply longer acting LA with a higher analgesic potency in an appropriate dosage and with an appropriate method of application.


Assuntos
Anestésicos Locais , Lidocaína , Orquiectomia , Dor , Procaína , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Animais , Animais Lactentes , Comportamento Animal/efeitos dos fármacos , Catecolaminas/sangue , Injeções/efeitos adversos , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Masculino , Orquiectomia/efeitos adversos , Orquiectomia/veterinária , Dor/tratamento farmacológico , Dor/etiologia , Dor/veterinária , Procaína/administração & dosagem , Procaína/farmacologia , Procaína/uso terapêutico , Estresse Fisiológico/efeitos dos fármacos , Suínos
13.
Pharmacology ; 104(3-4): 139-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203272

RESUMO

We studied the effect of lignocaine (LIG) on lung cancer cells. LIG dose- and concentration-dependently reduced the viability of the lung cancer cell line 95D. Fluorescence microscopy revealed that LIG-induced apoptosis, and this was confirmed via flow cytometric analysis of cells treated with various concentrations of LIG; the drug increased the proportions of cells in S-phase. Bad and Bax levels rose, and that of Bcl2 fell significantly, after addition of LIG; Western blotting showed that the drug also reduced the levels of phosphorylated proteins involved in downstream phosphoinositide 3-kinases/mammalian target of rapamycin/mammalian target of rapamycin signaling. In conclusion, our results suggest that LIG may be a useful therapy for human lung carcinoma.


Assuntos
Anestésicos Locais/farmacologia , Antineoplásicos/farmacologia , Lidocaína/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Fosforilação/efeitos dos fármacos , Fase S/efeitos dos fármacos
14.
Pharmacol Rep ; 71(4): 732-737, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207435

RESUMO

BACKGROUND: Dextrorphan with long-acting local anesthetic effects did not cause system toxicity as fast as bupivacaine, while catecholamines (i.e., epinephrine) with the vasoconstrictive characteristics enhanced the effects of local anesthetic drugs. The objective of the experiment was to examine the synergistic effect of local dopamine (a catecholamine) injection on cutaneous antinociception of dextrorphan. METHODS: The panniculus reflex in response to skin stimulation with a needle was used as the primary endpoint when dextrorphan (1.50, 2.61, 5.46, 10.20 and 20.40 µmol) alone, dopamine (16.20, 32.40, 51.60, 60.00 and 81.60 µmol) alone, or dopamine + dextrorphan (a ratio of ED50vs. ED50) was injected subcutaneously on the rat's back. We used an isobolographic modelling approach to determine whether a synergistic effect would be observed. RESULTS: We showed that dextrorphan, dopamine, or the mixture of dopamine and dextrorphan produced dose-related skin antinociception. The potency (ED50, 50% effective dose) for cutaneous antinociception was dextrorphan [6.02 (5.93-6.14) µmol] greater than dopamine [48.91 (48.80-49.06) µmol] (p < 0.01). The duration of nociceptive inhibition induced by dopamine was longer than that induced by dextrorphan (p < 0.01) based on their equipotent doses (ED25, ED50, and ED75). Enhancement and prolongation of skin antinociception occurred after co-administration of dopamine with dextrorphan. CONCLUSIONS: When compared to dopamine, dextrorphan was more potent and had a shorter duration of skin nociceptive block. Dopamine produced a synergistic effect on dextrorphan-mediated antinociception, and prolonged dextrorphan's antinociceptive duration.


Assuntos
Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Dextrorfano/farmacologia , Dopamina/farmacologia , Pele/efeitos dos fármacos , Analgésicos/administração & dosagem , Anestésicos Locais/administração & dosagem , Animais , Dextrorfano/administração & dosagem , Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Injeções Subcutâneas , Masculino , Ratos Sprague-Dawley
15.
Biochem Soc Trans ; 47(3): 919-932, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31085615

RESUMO

Biological membranes form the boundaries to cells. They are integral to cellular function, retaining the valuable components inside and preventing access of unwanted molecules. Many different classes of molecules demonstrate disruptive properties to the plasma membrane. These include alcohols, detergents and antimicrobial agents. Understanding this disruption and the mechanisms by which it can be mitigated is vital for improved therapeutics as well as enhanced industrial processes where the compounds produced can be toxic to the membrane. This mini-review describes the most common molecules that disrupt cell membranes along with a range of in vitro liposome-based techniques that can be used to monitor and delineate these disruptive processes.


Assuntos
Lipossomos , Modelos Biológicos , Anestésicos Locais/farmacologia , Anti-Infecciosos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Detergentes/farmacologia , Solventes/farmacologia
16.
Muscle Nerve ; 60(4): 367-375, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31107560

RESUMO

INTRODUCTION: Topical application of lidocaine-and-prilocaine (LP) cream attenuates the functionality of small cutaneous nerve fibers. The aim of this human study was to measure the underlying excitability modulation of small cutaneous nerve fibers using a novel and fast perception threshold tracking (PTT) technique. METHODS: Small sensory fibers were selectively blocked by 120-minute topical application of LP and confirmed by quantitative sensory testing. Excitability changes of small (activated by a specially designed pin electrode) and large (patch electrode) nerve fibers were assessed as the strength-duration relation and threshold electrotonus. RESULTS: The excitability assessed by the strength-duration relation and threshold electrotonus was significantly modulated for the small afferents (P < 0.05, Wilcoxon's test) but not the large afferents. DISCUSSION: This novel PTT technique was able to assess inhibition of membrane properties of small cutaneous fibers, suggesting the usefulness of the technique as a diagnostic method for assessing impairment of small fibers, as seen in many types of polyneuropathies.


Assuntos
Anestésicos Locais/farmacologia , Combinação Lidocaína e Prilocaína/farmacologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Neuropatia de Pequenas Fibras/diagnóstico , Administração Cutânea , Adulto , Estudos Cross-Over , Método Duplo-Cego , Estimulação Elétrica , Eletrodiagnóstico , Feminino , Voluntários Saudáveis , Humanos , Masculino , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Limiar Sensorial/fisiologia , Adulto Jovem
17.
Anesth Analg ; 128(6): 1336-1343, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31094809

RESUMO

BACKGROUND: The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture. METHODS: We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the "wheal" formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug-drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine. RESULTS: We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007-0.015] µmol) than for dibucaine (mean, 0.493 [95% CI, 0.435-0.560] µmol) (P < .01), while there were no significant differences between dibucaine and bupivacaine (mean, 0.450 [95% CI, 0.400-0.505] µmol). On the equipotent basis (75% effective dose, median effective dose, and 25% effective dose), sensory block duration provoked by epinephrine was greater (P < .01) than that provoked by dibucaine or bupivacaine. Coadministration of dibucaine with epinephrine produced a synergistic nociceptive block, whereas phentolamine blocked that synergistic block. CONCLUSIONS: The preclinical data indicated that there is no statistically significant difference between the potency and duration of dibucaine and bupivacaine in this model. Epinephrine synergistically enhances the effects of dibucaine, while phentolamine partially blocked those effects. α-Adrenergic receptors play an important role in controlling synergistic analgesic effect of dibucaine combined with epinephrine.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos/farmacologia , Bupivacaína/farmacologia , Dibucaína/farmacologia , Epinefrina/farmacologia , Fentolamina/farmacologia , Pele/efeitos dos fármacos , Analgesia , Anestésicos Locais/farmacologia , Animais , Área Sob a Curva , Relação Dose-Resposta a Droga , Interações de Medicamentos , Sinergismo Farmacológico , Injeções Subcutâneas , Masculino , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
18.
Vet Anaesth Analg ; 46(4): 492-495, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129046

RESUMO

OBJECTIVE: To compare the reaction to cephalic intravenous (IV) catheter placement with or without lidocaine-prilocaine cream in cats sedated with dexmedetomidine and methadone or nalbuphine. STUDY DESIGN: Prospective, randomized, blind study. ANIMALS: A group of 24 female mixed breed cats. METHODS: Cats were randomly allocated to one of the two sedation protocols: dexmedetomidine (0.01 mg kg-1) and methadone (0.3 mg kg-1; DEXMET) or dexmedetomidine (0.01 mg kg-1) and nalbuphine (0.3 mg kg-1; DEXNALB). Sedation was scored 30 minutes later using a visual analog scale. Subsequently, a 2 × 3.5 cm area of the antebrachium over the cephalic vein was clipped, and half the cats within each protocol were randomly assigned for topical lidocaine-prilocaine cream (treatment), whereas no cream was applied to other cats (control). After 20 minutes, an attempt was made to place a 24 gauge catheter into the cephalic vein and the reaction of the cats to this procedure was scored using a numeric scale 0-3. Sedation and catheterization reaction scores were compared between sedation protocols and whether cats were administered lidocaine-prilocaine cream or not using the Friedman test followed by the Bonferroni procedure. A p value < 0.05 was considered significant. RESULTS: Sedation scores were not different between sedation protocols or between treatment and control cats within each protocol. All cats administered lidocaine-prilocaine cream showed no reaction to IV catheter placement. Among the control cats, no response was observed in one cat in DEXNALB. Catheterization reaction score was lower in the treatment cats in both the sedation protocols when compared with their respective controls. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine-prilocaine cream applied for 20 minutes abolished the reaction to catheterization in cats sedated with dexmedetomidine and nalbuphine or methadone. Facilitation of IV catheter placement occurred within 20 minutes of lidocaine-prilocaine application.


Assuntos
Cateterismo Periférico/veterinária , Dexmedetomidina/farmacologia , Combinação Lidocaína e Prilocaína/farmacologia , Metadona/farmacologia , Nalbufina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Animais , Gatos , Dexmedetomidina/administração & dosagem , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Combinação Lidocaína e Prilocaína/administração & dosagem , Metadona/administração & dosagem , Nalbufina/administração & dosagem , Distribuição Aleatória
19.
Vet Anaesth Analg ; 46(4): 496-500, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076335

RESUMO

OBJECTIVE: To evaluate if intramuscular (IM) lidocaine potentiates the sedative effects of alfaxalone and results in cardiopulmonary changes in sedated bearded dragons. STUDY DESIGN: Prospective experimental crossover study. ANIMALS: A group of eight adult bearded dragons (Pogona vitticeps) weighing 334 ± 46 g. METHODS: Animals were administered alfaxalone (10 mg kg-1 subcutaneously) and 15 minutes later either lidocaine 2% (4 mg kg-1) or 0.9% sodium chloride (0.2 mL kg-1) was administered IM in the thoracic limb. The treatments were randomized and separated by 7 days. Sedation was scored based on body position, eye closure, jaw tone, swallowing, pick up response, righting reflex and pelvic limb withdrawal reflex. Heart rate (HR) and respiratory rate (fR) were recorded every 5 minutes until recovery from sedation. RESULTS: Lidocaine had no significant effect on duration or depth of alfaxalone sedation. HR increased significantly for <10 minutes following lidocaine administration by a median (interquartile range) of 33% (28-37%; p = 0.024). No clinically significant effects on fR occurred following lidocaine injection. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of lidocaine 2% (4 mg kg-1) IM did not potentiate alfaxalone sedation but resulted in a transient clinically relevant increase in HR.


Assuntos
Anestésicos Locais/farmacologia , Anestésicos/farmacologia , Lidocaína/farmacologia , Lagartos , Pregnanodionas/farmacologia , Anestésicos/administração & dosagem , Anestésicos Locais/administração & dosagem , Animais , Estudos Cross-Over , Feminino , Injeções Intramusculares , Lidocaína/administração & dosagem , Masculino , Pregnanodionas/administração & dosagem , Distribuição Aleatória
20.
Pol J Vet Sci ; 22(1): 31-35, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30997763

RESUMO

The aim of the study was to compare anaesthesia protocol utilizing combination ketamine/ medetomidine with epidural lidocaine or morphine to orthopaedic surgery in rabbits. All rabbits received intramuscularly medetomidine (0.5 mg/kg) and ketamine (20 mg/kg). In group L (n=13) epidural injection was performed with lidocaine (3 mg/kg) and in group M (n=13) with morphine (0.1 mg/kg) diluted with sterile saline to 0.6 ml. Rabbits underwent bilateral mosaicplasty surgery. Heart rate (HR), systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP), arte- rial oxygen saturation (SpO2) and respiratory rate (RR) were measured every 5 minute during surgical procedure. Duration of sensory blockade was measured based on toe pinch reflex and recorded. Hemodynamic parameters were comparable at baseline in both groups. We did not observe significant differences in HR, RR, SBP, DBP, MAP between group L and M. Intragroup statistical analysis revealed differences at different time points in group M in terms of HR, SBP, DBP, MAP. In rabbits in group M blood pressure dropped while HR increased over time. In both groups a decrease in SpO2 was observed. Mean duration of loss of the toe pinch reflex was similar between group L and M, and amounted to 72.79±34.48 and 82.80±17.85 minutes, respectively.


Assuntos
Lidocaína/administração & dosagem , Lidocaína/farmacologia , Morfina/administração & dosagem , Morfina/farmacologia , Dor Pós-Operatória/veterinária , Coelhos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Anestesia/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Animais , Pressão Sanguínea , Membro Posterior/cirurgia , Injeções Epidurais , Ketamina/administração & dosagem , Ketamina/farmacologia , Medetomidina/administração & dosagem , Medetomidina/farmacologia , Dor Pós-Operatória/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA