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Controle da dor e inflamação em cirurgia odontológicaGaujac, Cristiano [UNESP] 22 February 2006 (has links) (PDF)
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gaujac_c_me_araca.pdf: 216269 bytes, checksum: 81a5fdfaa37a3ba2d8b2c9f81fe5d9b6 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A dor pode fazer parte ou não do processo inflamatório e significar a presença de dano ao organismo. É por meio dela que a maioria das afecções se manifesta. O cirurgião-dentista é responsável pela orientação ao paciente a respeito da dor esperada e sobre a estratégia de suavizá-la. Esse trabalho tem por objetivo elaborar um manual para que se possa fornecer aos clínicos e aos alunos de graduação informações e embasamento necessário para realizar uma prescrição medicamentosa adequada para a dor aguda, sendo sugeridos alguns protocolos de atendimento. / Pain represents a mechanism which can participate or not of the inflammatory process causing injury to the organism. Most of the affections are manifested through the pain. The dental surgeon is responsible for the patient's orientation regarding the expected pain and also about the strategy to soothe this expectation. This study aims to elaborate a practical manual in order to offer to the dental professionals and also to the undergraduate students information and enough background to accomplish an adequate prescription for the acute pain suggesting suitable clinical protocols.
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Atividade antinociceptiva orofacial do (S)-(-)-álcool perílico em camundongos: um estudo controlado, randomizado e triplo-cegoMorais, James Felipe Tomaz de 01 December 2015 (has links)
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Previous issue date: 2015-12-01 / Monoterpenes are the major bioactive compounds found in essential oils from
medicinal plants used in the treatment of diseases. Among these, (S)-(-)-perillyl
alcohol (PA) stands as a promising molecule with antitumor, anti-inflammatory and
antioxidant properties. This study investigated the antinociceptive effects of PA on
orofacial nociception in Swiss male mice using tests of formalin-, capsaicin-, and
glutamate-induced pain. For each test, eight animals per group were pretreated
intraperitoneally by a blinded investigator with PA (50 and 75 mg/kg, i.p.), morphine (5
mg/kg, i.p.) or vehicle (saline + 0.2% Tween 80). The treatment was performed thirty
minutes before the induction of orofacial nociception by injecting formalin (20 µl, 2%),
capsaicin (20 µl, 2.5 µg) or glutamate (40 µl, 25 mM) solution in the right area of the
upper lip. The orofacial nociceptive behavior was timed in all tests by an investigator
blinded to the treatments. Statistical analysis was performed by a blinded researcher.
Groups were compared with Mann-Whitney’s test and the correlation was calculated
with Spearman’s correlation test, describing its median and interquartile range. The
magnitude of statistical analysis was also analyzed with confidence intervals, effect
size and power. The results indicate that PA blocked the orofacial nociceptive
behavior at all tested doses (P <.05) similarly to morphine (P > .05) in the formalin,
capsaicin and glutamate tests. Effect size was high in phase I of formalin test for 50
mg/kg and 75 mg/kg of PA (CI95%: 2,32/0,48; power: 84% and CI95%: 2,76/0,82;
power: 96.2%, respectively), 75 mg/kg of PA in phase II (CI95%: 2,26/0,44; power:
82.3%) and for 75 mg/kg of PA in glutamate test (CI95=3,16/1,11; power: 99.2%).
These findings confirm a strong evidence of antinociceptive properties of PA in the
orofacial region considering high values of power observed in formalin and glutamate
models, suggesting it as a potential substance for the treatment of clinical conditions
involving orofacial pain. / Os monoterpenos são os principais componentes bioativos encontrados em óleos
essenciais de plantas com uso medicinal para o tratamento de doenças. Dentre eles,
o (S)-(-)-álcool perílico (AP) representa uma molécula promissora com atividades
antitumoral, anti-inflamatória e antioxidantes. O presente estudo investigou os efeitos
antinociceptivos do AP na nocicepção orofacial em camundongos suíços utilizando os
testes de dor induzida por formalina, capsaicina e glutamato. Para cada teste, oito
animais por grupo foram pré-tratados via intraperitoneal (i.p.) por um investigador
cego com AP (50 e 57 mg/kg, i.p.), morfina (5 mg/kg, i.p.) ou veículo (salina + Tween
80 0.2%). O tratamento foi realizado trinta minutos antes da indução da nocicepção
orofacial através da injeção de uma solução de formalina (20 µl, 2%), capsaicina (20
µl, 2.5µg) ou glutamato (40 µl, 25 mM) no lábio superior direito do animal utilizando
uma agulha calibre 27G. O tempo de comportamento de nocicepção orofacial foi
medido por um investigador cego para os grupos de tratamento, assim como a
análise estatística. Os grupos foram comparados utilizando o teste de Mann-Whitney
e a correlação entre as doses foi calculada pelo teste de correlação de Spearman,
descrevendo para cada grupo os valores de mediana e distância interquartil. A
magnitude da análise estatística foi verificada com os intervalos de confiança,
magnitude do efeito e poder. Os resultados indicaram que o AP bloqueou o
comportamento de nocicepção orofacial em todas as doses testadas (p <,05) de
modo similar à morfina (p <,05) nos testes da formalina, capsaicina e glutamato. A
magnitude do efeito foi alta para a fase 1 do teste da formalina nas doses de 50 e 75
mg/kg de AP (IC95%: 2,32/0,48; poder: 84% e IC95%: 2,76/0,82; poder: 96,2%,
respectivamente), assim como na dose de 75 mg/kg na fase II do teste da formalina
(IC95%: 2,26/0,44; poder: 82,3%) e no teste do glutamato (IC95=3,16/1,11; poder:
99,2%). Os testes com AP confirmam uma forte evidência de sua atividade
antinociceptiva considerando os altos valores de poder principalmente nos modelos
da formalina e glutamato, sendo assim uma substância potencial para o tratamento
de condições clínicas envolvendo dor orofacial.
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Estudo comparativo do emprego de tramadol, codeína e cetoprofeno no controle da dor pós-operatória e nos níveis de glicose, cortisol e interleucina-6 em cães submetidos à maxilectomia ou mandibulectomia / Comparative study of the effects of tramadol, codeine, ketoprofen and combinations on postoperative pain and on levels of blood glucose, serum cortisol and interleukin-6 in dogs undergoing maxillectomy and mandibulectomyTeresinha Luiza Martins 24 August 2009 (has links)
Embora existam muitos estudos clínicos avaliando analgésicos e o controle da dor em cães, poucos são realizados em animais com dor do câncer e submetidos a procedimento cirúrgico para ressecção da neoplasia como a maxilectomia e mandibulectomia. Este estudo clínico foi realizado de forma prospectiva, comparativa, aleatória e de maneira simples cego com o propósito de avaliar a eficácia analgésica de diferentes tratamentos no período pós-operatório em cães submetidos à maxilectomia ou mandibulectomia. Foram utilizados no estudo 42 cães com neoplasia oral. Todos os animais foram prémedicados com acepromazina (0,05mg/kg) associado à meperidina (2mg/kg) por via intramuscular e a anestesia foi induzida com propofol por via iv na dose suficiente realizar a intubação (2.3-6.5mg/kg). O isoflurano foi utilizado para a manutenção da anestesia. Trinta minutos antes do fim do procedimento cirúrgico, os cães foram distribuídos aleatoriamente em um dos 5 diferentes grupos para analgesia pósoperatória: tramadol 2mg/kg (Tra), codeína 2mg/kg (Co), cetoprofeno 2mg/kg (Ce), tramadol 2mg/kg associado ao cetoprofeno 2mg/kg (TraCe) ou codeína 2mg/kg associado ao cetoprofeno 2mg/kg (CoCe), por via subcutânea. A freqüência cardíaca (FC) e respiratória (FR), pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão arterial média (PAM), glicose sanguínea, cortisol e interleucina-6 (IL- 6) e grau de sedação foram verificados até 24 horas, e grau de analgesia foi verificado por até 120 horas do início da administração do analgésico, ou seja, os respectivos tratamentos foram mantidos por 5 dias da seguinte forma: tramadol ou codeína a cada 8 horas e cetoprofeno a cada 24 horas por via oral (MBL, M1, M2, M3, M4, M5, M24, M48, M72, M96 e M120). O resgate analgésico foi realizado nos animais que apresentaram escore de dor 4 em qualquer momento do estudo (dipirona 25mg/kg e morfina 0,1mg/kg). A análise estatística foi realizada por meio do Kruskal-Wallis, Friedman para mensurações repetidas, ANOVA e teste 2. Os gráficos em boxplot ou diagrama em caixas representam a distribuição dos dados. Os valores com p<0,05 foram considerados significantes. Não houve diferença entre os grupos de tratamento com relação ao peso, tempo de cirurgia, tempo para extubação, FC, FR, PAS, PAD e PAM, cortisol e IL-6 séricos, e escore de dor pela escala de análise descritiva. A concentração da glicose sanguínea aumentou de forma significante com relação aos valores basais no grupo Tra (M5= 96±14), Co (M1= 120±66 e M3=96±21), Ce (M5= 105±22) e CoCe (M3=104±16). Aumento do escore de dor foi observado no M2 do grupo Tra em relação a MBL e M1 a M5 do grupo Co em relação a M120 (p<0,05), contudo a média do escore não foi maior que 2,7. Baixo grau de sedação ainda foi observado no grupo CoCe no M24 (0,1±0,4 p<0,001) com relação ao M1. O número de resgate foi baixo, totalizando 19 administrações. No grupo Ce houve maior necessidade de resgate analgésico. Com base nos resultados obtidos, pôde-se concluir que os grupos de tratamento analgésico promoveram controle da dor pós-operatória de boa qualidade na maioria dos cães do estudo e com baixa incidência de efeitos adversos, podendo ser indicados no controle da dor em procedimentos de maxilectomia e mandibulectomia. / Although there are many clinical studies evaluating analgesics and pain control in dogs, very few were carried out in animals with cancer pain, and submitted to oncologic surgery with tumor resections such as maxillectomy and mandibulectomy. This clinical, prospective, randomized, simple blinded study was performed with the purpose of evaluating analgesic efficacy of different treatments in the postoperative period in dogs submitted to maxillectomy or mandibulectomy. Forty-two client-owned dogs with oral tumor were used in the study. Dogs were premedicated with acepromazine (0.05mg kg-1) and meperidine (2mg kg-1) by the intramuscular route and anesthesia was induced with intravenous propofol in a dose sufficient to allow intubation (2.3-6.5mg-1). Isoflurane was used for maintenance of anesthesia. Thirty minutes prior to the end of surgery, dogs were randomly allocated in one of 5 different groups for postoperative analgesia: tramadol 2mg kg-1 (Tra), codeine 2mg kg-1 (Co), ketoprofen 2mg kg-1 (Ke), tramadol 2mg kg-1 + ketoprofen 2mg kg-1 (TraKe) or codeine 2mg kg-1 + ketoprofen 2mg kg-1 (CoKe), subcutaneously. Heart (HR) and respiratory (RR) rates, systolic (SBP), median (MBP) and diastolic (DBP) blood pressures, blood glucose, serum cortisol and interleukin-6 (IL-6) and degree of sedation were recorded for 24 hours, and degree of analgesia were evaluated until 120 hours of the start of analgesic administration (MBL, M1, M2, M3, M4, M5, M24, M48, M72, M96 and M120), being that treatments were maintained for 5 days as follows: codeine or tramadol every 8 hours and the ketoprofen every 24 hours orally. Analgesic rescue was delivered to animals with pain scores equal or superior to 4 at any time of the study (dypirone 25mg -1 and morphine 0,1mg-1). Statistical analyses were performed by means of the Kruskal-Wallis, Friedmann for repeated measures, ANOVA and 2 tests. Graphics boxplot or box diagrams represents dates of distribution. Values of p<0.05 were considered significant. There were no differences between groups related to weight, surgical time, extubation time, HR, RR, SBP, MBP, DBP, serum cortisol and IL-6, and pain score by Descriptive Scale (DS). Blood glucose concentrations were significantly increased in relation to baseline, in groups Tra (M5= 96±14), Co (M1= 120±66 e M3=96±21), Ke (M5= 105±22) and CoKe (M3=104±16). Increase of pain score was observed in M2 of group Tra in relation to baseline, and M1 to M5 of group Co in relation to M120 (p<0,05), however the average score was not higher than 2.7. Low level of sedation was also observed in group CoKe in M24 (0.1 ± 0.4 - p <0.001) compared to M1.. The number of rescue was low, totaling 19 administrations. Ke group required more analgesic rescue. So, it can be conclude that treatment analgesic groups promoted a good quality pain control of postoperative in most of the dogs in the study and with low incidence of side effects, could be indicated in the control of the pain in procedures of maxillectomy and mandibulectomy.
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Fentanyl and Other Opioid Involvement in Methamphetamine-Related DeathsDai, Zheng, Abate, Marie A., Groth, Caroline P., Rucker, Tori, Kraner, James C., Mock, Allen R., Smith, Gordon S. 04 March 2022 (has links)
: Methamphetamine-related deaths have been rising along with those involving synthetic opioids, mostly fentanyl and fentanyl analogs (FAs). However, the extent to which methamphetamine involvement in deaths differs from those changes occurring in synthetic opioid involvement is unknown.: To determine the patterns and temporal changes in methamphetamine-related deaths with and without other drug involvement.: Data from all methamphetamine-related deaths in West Virginia from 2013 to 2018 were analyzed. Quasi-Poisson regression analyses over time were conducted to compare the rates of change in death counts among methamphetamine and fentanyl//FA subgroups.: A total of 815 methamphetamine-related deaths were analyzed; 572 (70.2%) were male and 527 (64.7%) involved an opioid. The proportion of methamphetamine only deaths stayed relatively flat over time although the actual numbers of deaths increased. Combined fentanyl/FAs and methamphetamine were involved in 337 deaths (41.3%) and constituted the largest increase from 2013 to 2018. The modeling of monthly death counts in 2017-2018 found that the average number of deaths involving fentanyl without methamphetamine significantly declined (rate of change -0.025, < .001), while concomitant fentanyl with methamphetamine and methamphetamine only death counts increased significantly (rate of change 0.056 and 0.057, respectively, < .001).: Fentanyl and FAs played an increasingly significant role in methamphetamine-related deaths. The accelerating number of deaths involving fentanyl/FAs and methamphetamine indicates the importance of stimulants and opioids in unintentional deaths. Comprehensive surveillance efforts should continue to track substance use patterns to ensure that appropriate prevention programs are undertaken.
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Primary Care Physicians' Opioid-Related Prevention Behaviors and Intentions: A Descriptive AnalysisMelton, Tyler C., Hagemeier, Nicholas E., Tudiver, Fred G., Foster, Kelly N., Arnold, Jessie, Brooks, Bill, Alamian, Arsham, Pack, Robert P. 01 January 2022 (has links)
OBJECTIVE: Primary care physicians (PCPs) are positioned to mitigate opioid morbidity and mortality, but their engagement in primary, secondary, and tertiary opioid-related prevention behaviors is unclear. The objective of this study was to evaluate Tennessee PCPs' engagement in and intention to engage in multiple opioid-related prevention behaviors. METHODS: A survey instrument was developed, pretested, and pilot tested with practicing PCPs. Thereafter, a census of eligible Tennessee PCPs was conducted using a modified, four-wave tailored design method approach. Three patient scenarios were employed to assess physician intention to engage in 10 primary, secondary, and tertiary prevention behaviors. Respondents were asked to report, given 10 similar scenarios, the number of times (0-10) they would engage in prevention behaviors. Descriptive statistics were calculated using SPSS version 25. RESULTS: A total of 296 usable responses were received. Physician intention to engage in prevention behaviors varied across the 10 behaviors studied. Physicians reported frequently communicating risks associated with prescription opioids to patients (8.9 ± 2.8 out of 10 patients), infrequently utilizing brief questionnaires to assess for risk of opioid misuse (1.7 ± 3.3 out of 10 patients), and screening for current opioid misuse (3.1 ± 4.3 out of 10 patients). Physicians reported seldomly co-prescribing naloxone for overdose reversal and frequently discharging from practice patients presenting with an opioid use disorder. CONCLUSIONS: This study noted strengths and opportunities to increase engagement in prevention behaviors. Understanding PCPs' engagement in opioid-related prevention behaviors is important to effectively target and implement morbidity and mortality reducing interventions.
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Impact of State Legislation in Tennessee on Opioid Prescribing Practices of Orthopedic SurgeonsGuidry, Corey, Dema, Blerim, Allen, Corinne, Stewart, David 01 March 2022 (has links)
OBJECTIVE: Post-operative patients are at increased risk of becoming chronic users of opioids, and overprescribing can lead to abuse and diversion. Though data have shown a decrease in opioid prescriptions nationally, limited studies have specifically evaluated the influence of state legislation on this trend. This study aimed to assess the impact of legislation in the state of Tennessee on opioid prescribing amongst orthopedic surgeons. DESIGN: This retrospective cohort analysis evaluated patients who received opioids post-orthopedic surgery before and after the state legislation was passed. SETTING: A community teaching hospital. PATIENTS AND PARTICIPANTS: Two hundred and three post-orthopedic surgery patients were included, with 101 in the preleg-islation and 102 in the post-legislation groups. INTERVENTIONS: State legislation in Tennessee limiting amounts of prescribed opioids went into effect in July 2018. MAIN OUTCOME MEASURE(S): The primary outcome was total morphine milligram equivalents (MMEs) prescribed, with secondary outcomes of days' supply, dosage units, and MME per day. RESULTS: Orthopedic surgery patients in the post-legislation arm were prescribed significantly fewer MME than those in the prelegislation arm (median MME 375 vs. 562.5; p < 0.001). Prescription days' supply, number of dosage units, and MME per day were also significant lower in the post-legislation group. CONCLUSIONS: After orthopedic surgery, patients in the post-legislation arm were prescribed a median 187.5 MME less than those in the prelegislation arm. Our findings suggest that state opioid legislation is associated with a reduction in the amount of opioids prescribed in certain orthopedic surgery patients, though further studies evaluating adequacy of pain control are warranted.
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Sexual Minority Disparities in Opioid and Benzodiazepine Misuse Among Adults With Opioid Use DisorderStruble, Cara A., Thomas, Kathryn, Stenersen, Madeline R., Moore, Kelly E., Burke, Catherine, Pittman, Brian, McKee, Sherry A. 01 May 2022 (has links)
BACKGROUND AND OBJECTIVES: Sexual minority individuals demonstrate disparate rates of substance use. Research suggests that bisexual women are vulnerable to substance use disorders when compared to other sexual minority groups. This study explored differences in prevalence of past-year alcohol use disorder (AUD) with and without concurrent past-year opioid and/or benzodiazepine misuse. METHODS: The present study utilized responses from the National Survey on Drug Use and Health (NSDUH) public dataset between the years 2015-2019 (N = 16,002) to examine the association between sexual orientation and concurrent misuse of opioids and/or benzodiazepines among individuals with past-year AUD, stratified by sex. RESULTS: Bisexual females demonstrated higher rates of concurrent opioid and benzodiazepine use compared to all other groups. Although there was no association between sexual orientation and concurrent substance use patterns among males, female respondents with past-year AUD endorsing past-year misuse of opioids and benzodiazepines, both alone and in combination, were more likely to be bisexual compared to heterosexual. Lesbians were less likely to endorse concurrent misuse of opioids and benzodiazepines compared to bisexual females. DISCUSSION AND CONCLUSIONS: In a national sample, bisexual females demonstrated higher odds of risky concurrent substance use patterns. Identifying sexual minority individuals who exhibit elevated risk of co-occurring alcohol, opioid, and/or benzodiazepine misuse is an important step to targeted prevention efforts and allocation of resources to combat rising overdose deaths. SCIENTIFIC SIGNIFICANCE: For the first time, this study explored risky concurrent alcohol, opioid, and benzodiazepine misuse patterns among individuals of different sexual orientations.
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Epidemiology and routine care treatment of patients with hip or knee osteoarthritis and chronic lower back pain: real-world evidence from GermanyHradetzky, E., Ohlmeier, C., Brinkmann, C., Schild, M., Galetzka, W., Schmedt, N., John, T., Kaleth, D., Gothe, H. 06 June 2024 (has links)
Aim Musculoskeletal disorders are a major public health problem in most developed countries. As a main cause of chronic pain, they have resulted in an increasing prescription of opioids worldwide. With regard to the situation in Germany, this study aimed at estimating the prevalence of musculoskeletal diseases such as chronic low back pain (CLBP) and hip/knee osteoarthritis (OA) and at depicting the applied treatment patterns. - Subject and methods German claims data from the InGef Research Database were analyzed over a 6-year period (2011–2016). The dataset contains over 4 million people, enrolled in German statutory health insurances. Inpatient and outpatient diagnoses were considered for case identification of hip/knee OA and CLBP. The World Health Organization (WHO) analgesic ladder was applied to categorize patients according to their pain management interventions. Information on demographics, comorbidities, and adjuvant medication was collected. - Results In 2016, n = 2,693,481 individuals (50.5% female, 49.5% male) were assigned to the study population; 62.5% of them were aged 18–60 years. In 2016, n = 146,443 patients (5.4%) with CLBP and n = 307,256 patients (11.4%) with hip/ knee OA were identified. Of those with pre-specified pain management interventions (CLBP: 66.3%; hip/knee OA: 65.1%), most patients received WHO I class drugs (CLBP: 73.6%; hip/knee OA: 68.7%) as the highest level. - Conclusion This study provides indications that CLBP and hip/knee OA are common chronic pain conditions in Germany, which are often subjected to pharmacological pain management. Compared to non-opioid analgesic prescriptions of the WHO I class, the dispensation of WHO class II and III opioids was markedly lower, though present to a considerable extent.
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Antioxidative, analgesic and anti-inflammatory activities of Acokanthera oppositifolia, Plantago lanceolata, Conyza canadensis, and Artemisia vulgarisOndua, Moise 02 1900 (has links)
The anti-inflammatory properties of four medicinal plants were investigated. These plant extracts were subjected to screening for their possible effects as antioxidative, analgesic, and anti-inflammatory agents. In the antioxidant activity, the Plantago lancelota extracts resulted in an IC50 value of 0.4 mg/mL compared to the positive control quecertin with IC50 0.04 mg/mL Plantago lanceolata inhibited COX-2 activity with IC50 values of 0.41 mg/mL. However, the COX-1 inhibition indicated an IC50 of 68.99 mg/mL. The lipoxygenase assay indicated that Plantago lanceolata was the most active plant species with an IC50 value of 4.86 mg/mL compared to the positive control (quecertin) with an IC50<2mg/mL. The nitric oxide assay of the plant extracts indicates a dose-dependent activity of our plant extracts. Likewise the cell viability result indicated a good activity at dose 100 mg/mL. / Life and Consumer Sciences / M. Sc. (Life Sciences)
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Farmakološki efekti etarskog ulja ruzmarina Rosmarinus officinalis, L. (Lamiaceae), na miševima soja NMRI-Haan i pacovima soja Wistar / Pharmacological effects of rosemary essential oil Rosmarinus officinalis, L. (Lamiaceae), on mice of strain NMRI-Haan and rats of strain WistarMilanović Isidora 09 July 2015 (has links)
<p>Ruzmarin Rosmarinus officinalis L. (Lamiaceae) je biljka koja se u tradicionalnoj medicini na našem području koristi za postizanje analgetičkog, holeretičkog i hepatoprotektivnog delovanja. Prema Evropskoj agenciji za lekove (2010 godine), indikacije za sistemsku primenu etarskog ulja ruzmarina su lečenje dispepsije i spazama gastrointestinalnog trakta, a za spoljašnju primenu se preporučuje u lečenju umereno jakih bolova u zglobovima i mišićima i u lečenju poremećaja periferne cirkulacije. Imajući u vidu da komponente etarskog ulja ruzmarina ispoljavaju i druga, potencijalno korisna farmakološka svojstva, postoji potreba da se ova delovanja detaljnije ispitaju. Ciljevi ispitivanja su bili da se utvrdi: 1) analgetički efekat etarskog ulja ruzmarina i njegov uticaj na farmakodinamske osobine paracetamola, kodeina, diazepama i pentobarbitala kao i na farmakokinetske osobine paracetamola; 2) antioksidativni i hepatoprotektivni efekat u uslovima hemijski izazvanog oksidativnog stresa. Metodom gasne hromatografije (GC/MS i GC/FID) utvrđen je kvantitativni sastav etarskog ulja. Najzastupljenije komponente ulja koje je korišćeno u našem ispitivanju su oksidovani monoterpeni 1,8-cineol (43.77%) i kamfor (12.53%) i monoterpenski ugljovodonik α-pinen (11.51%). Suspenzija etarskog ulja ruzmarina primenjivana je miševima u dozama 10 i 20 mg/kg tm tokom sedam dana i jednokratno u farmakodinamskim testovima: test vrele ploče, test „uvijanja“ (posle intraperitonealne primene sirćetne kiseline), test za procenu motorne koordinacije životinja na rotirajućem štapu i test merenja vremena trajanja spavanja. Za ispitivanje uticaja etarskog ulja ruzmarina na farmakokinetske osobine paracetamola i za biohemijska i toksikološka ispitivanja, korišćeni su pacovi koji su tokom sedam dana tretirani suspenzijom etarskog ulja ruzmarina u dozi 5 i 10 mg/kg tm, a sedmog dana su primili paracetamol i.v. ili p.o.. Za praćenje farmakokinetskih parametara korišćeni su uzorci krvi dobijeni iz repne vene pacova u kojima su HPLC metodom merene koncentracije paracetamola, na osnovu kojih su potom određeni farmakokinetski parametri ovog leka. Antioksidativna aktivnost etarskog ulja ruzmarina je određivana in vitro (DPPH i Folin-Ciocaulteu testovima) i in vivo. Nakon žrtvovanja životinja iz prikupljenih uzoraka krvi određivani su iz seruma biohemijski parametri, pokazatelji bubrežne i jetrene funkcije, a u homogenatu tkiva jetre određivani su parametri oksidativnog stresa. Samo etarsko ulje ruzmarina ispoljava analgetičko delovanje i smanjuje visceralnu bol izazvanu sirćetnom kiselinom. Pored toga, potencira analgetički efekat kodeina i paracetamola. Etarsko ulje ruzmarina značajno smanjuje hipnotičko delovanje pentobarbitala i sprečava poremećaj motorne koordinacije nakon primene diazepama. Etarsko ulje ruzmarina ne utiče značajnije na oralnu biološku raspoloživost paracetamola. Višekratna primena različitih doza etarskog ulja ruzmarina ne izaziva toksične promene u krvi i jetri ispitivanih životinja. Primena etarskog ulja ruzmarina štiti životinje od reaktivnih kiseoničnih vrsta, umanjuje posledice izloženosti oksidativnom stresu i ispoljava značajno hepatoprotektivno delovanje.</p> / <p>Rosemary Rosmarinus officinalis, L.(Lamiaceae) is traditionally used in folk medicine for its analgetic, choleretic and hepatoprotective properties. According to the recommendation of European Medicines Agency from 2010, rosemary essential oil can be used for treating dyspepsia and mild spasmodic disorders of the gastrointestinal tract, and also externally as an adjuvant in the relief of minor muscular and articular pain and minor peripheral circulatory disorders. Different studies conducted with rosemary essential oil show other pharmacological effects of main components of the oil. The aim of this study was to examine: 1) analgetic effects of rosemary essential oil and its influence on the pharmacodynamic properties of paracetamol, codeine, diazepam and pentobarbital, and also its influence on the pharmacokinetic properties of paracetamol; 2) antioxidant and hepatoprotective effects on the parameters of chemicaly induced oxidative stress. The quantification of chemical constituents of the essential oil was carried out by gas chromatography (GC/FID and GC/MS). The major compounds that were identified and quantitated by GC-FID and GC-MS were oxygenated monoterpens 1,8-cineole (43.77%), camphor (12.53%) and monoterpene hydrocarbon α-pinene (11.51%). The suspension of rosemary essential oil was applied to mice orally (doses: 10 and 20 mg/kg b.w.) for seven days and in single dose for the pharmacodynamic tests: hot plate, writhing, rotharod and sleeping time. Rats treated with suspension of rosemary essential oil for seven days orally (doses: 5 and 10 mg/kg b.w.) were used for the examination of influence of essential oil on the pharmacokinetic properties of paracetamol. Then on the 7th day the paracetamol was applied to them p.o. or i.v.. The parameters of pharmacokinetic were analyzed in blood samples obtained from rats tail veins. The HPLC method was used for measurement of concentration of paracetamol in blood samples. Those concentrations were used for calculation of the pharmacokinetic parameters. The antioxidant activity of the rosemary essential oil was evaluated in vitro (with DPPH and Folin-Ciocaulteu tests) and in vivo. The animals were sacrificed and the samples of blood and liver were taken. The obtained serum was used for determination of standard biochemical parameters and the parameters of oxidative stress were analyzed in obtained liver homogenates. The essential oil of rosemary shows analgetic properties and it decreases visceral pain induced with intraperitoneally injected acetic acid. The rosemary essential oil increases pharmacological effects of codeine and paracetamol. Also, this oil reduces pentobarbital-induced sleeping time and diminishes diazepam-induced disorder of psychomotor coordination. The essential oil of rosemary does not change paracetamol bioavailability. The rosemary essential oil applied in multiple doses does not induce toxic changes in blood and liver samples obtained from animals. The use of rosemary essential oil protects animals from reactive oxygen species, decreases the effects caused by oxidative stress and shows significant hepatoprotective effect.</p>
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