Antiproliferative piperidine alkaloids from giant taro (Alocasia macrorrhiza) / 中国天然药物

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.

The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway

BACKGROUND: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. METHODS: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. RESULTS: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, ß-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. CONCLUSIONS: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/ß-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.

Rimonabant improves metabolic parameters partially attributed to restoration of high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice

Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice. Then, real-time PCR and electrophysiology were used to explore the contribution of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD feeding caused body weight gain, and decreased glucose/insulin tolerance in mice compared to those in the regular diet group (P<0.05), which was restored by rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the control group. Daily treatment with rimonabant for 5 weeks was shown to counter such decrease (P<0.05). Collectively, our findings provided a novel understanding for peripheral CB1R's role in the modulation of body weight and glucose homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as potential targets for obesity treatment.

EGF Induced RET Inhibitor Resistance in CCDC6-RET Lung Cancer Cells

PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.

Comparison of Dexmedetomidine and Remifentanil on Airway Reflex and Hemodynamic Changes during Recovery after Craniotomy

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.

Remifentanil protects uterus against ischemia-reperfusion injury in rats

PURPOSE: To investigate the effects of remifentanil as an antioxidant and analyze the histopathologic, biochemical changes in experimental ischemia-reperfusion (I/R) exposed rat uteri. METHODS: Wistar albino rats were assigned to three groups (n = 7). 2h period of ischemia was followed by 1h of reperfusion in the I/R and the I/R-remifentanil groups. After ischemia, no drug was administered in the sham and I/R groups. In the I/R-remifentanil group, remifentanil infusion (2 μg/kg/min) was started in the ischemia period, and continued until the end of reperfusion. After the ischemic and reperfusion period, the ischemic uterine horns were removed surgically for biochemical and histopathologic examination. Tissue damage scores (endometrial epithelial glandular leukocytosis, degeneration, and endometrial stromal changes) were examined. Malondialdehyde levels and catalase, superoxide dismutase enzyme activities in tissue were measured. RESULTS: We found significantly lower epithelial leukocytosis and cell degeneration in the I/R-remifentanil group (p<0.05). Remifentanil administration significantly decreased concentrations of malondialdehyde, and increased catalase and superoxide dismutase enzyme activities (p<0.05). CONCLUSION: Remifentanil appears to protect the uterine tissue against ischemia-reperfusion and can be used safely in uterus transplantation.

Some current challenges in research on air pollution and health / Desafíos actuales de la investigación sobre contaminación del aire y salud

This commentary addresses some of the diverse questions of current interest with regard to the health effects of air pollution, including exposure-response relationships, toxicity of inhaled particles and risks to health, multipollutant mixtures, traffic-related pollution, accountability research, and issues with susceptibility and vulnerability. It considers the challenges posed to researchers as they attempt to provide useful evidence for policy-makers relevant to these issues. This commentary accompanies papers giving the results from the ESCALA project, a multi-city study in Latin America that has an overall goal of providing policy-relevant results. While progress has been made in improving air quality, driven by epidemiological evidence that air pollution is adversely affecting public health, the research questions have become more subtle and challenging as levels of air pollution dropped. More research is still needed, but also novel methods and approaches to address these new questions.

Este comentario aborda algunos de los temas de interés actual en relación con los efectos de la contaminación del aire sobre la salud, tales como las relaciones exposición-respuesta, la toxicidad y riesgos para la salud de las partículas inhaladas, las mezclas de contaminantes múltiples, la contaminación relacionada con el tráfico, la investigación sobre responsabilidad, y los problemas de susceptibilidad y vulnerabilidad. Considera los retos que se presentan a los investigadores que intentan proporcionar evidencia para los responsables políticos en estas cuestiones. Este texto acompaña otros trabajos con resultados del proyecto ESCALA, un estudio en varias ciudades de América Latina que tiene como objetivo general proporcionar resultados relevantes para la política pública. Aunque ha habido avances para mejorar la calidad del aire, gracias a la evidencia epidemiológica de que la contaminación aérea está afectando negativamente a la salud pública, las preguntas de investigación se han vuelto más sutiles y difíciles a medida que los niveles de contaminación se reducen. Se necesita más investigación, pero también nuevos métodos y enfoques capaces de enfrentar estas preguntas.

Crescimento de bactérias em agentes de infusão: propofol 2% sustenta o crescimento, enquanto remifentanil e pantoprazol não / The growth of bacteria in infusion drugs: propofol 2% supports growth when remifentanil and pantoprazole do not / Crecimiento de bacterias en agentes de infusión: el propofol al 2% sustenta el crecimiento, mientras que el remifentanilo y el pantoprazol no

EXPERIÊNCIA E OBJETIVOS: Foram avaliados os riscos da contaminação de propofol 2%, remifentanil e pantoprazol e os efeitos desses agentes in vitro no crescimento de agentes infecciosos comuns em unidades de terapia intensiva. MÉTODOS: Para a detecção do risco de contaminação, foram testados agentes preparados para uso imediato em condições de unidade de terapia intensiva. Também foram investigados os efeitos desses três agentes no crescimento bacteriano. Os agentes foram preparados nas concentrações utilizadas na unidade de terapia intensiva e inoculados com patógenos comuns; em seguida, foram incubados a 4ºC, 22ºC e 36ºC. Foram obtidas subculturas a 0, 2, 4 e 8 h e avaliadas as contagens de colônias. Foram determinados os valores de concentração inibitória mínima para todos os agentes a 4ºC, 22ºC e 36ºC. RESULTADOS: Não foi observado crescimento nos agentes preparados na unidade de terapia intensiva. Propofol tendeu a suportar o crescimento, enquanto que remifentanil inibiu o crescimento bacteriano. O efeito de pantoprazol foi variável, dependendo com a bactéria testada. Nenhum dos agentes demonstrou atividade antibacteriana nas concentrações máximas que podem ser alcançadas no sangue dos pacientes. CONCLUSÃO: Propofol sustenta vigorosamente o crescimento dos microrganismos testados, o que não ocorre com remifentanil e pantoprazol. Portanto, é importante que sejam praticadas técnicas assépticas rígidas na preparação de propofol.

BACKGROUND AND OBJECTIVES: Contamination risks of propofol 2%, remifentanil, and pantoprazole; and in vitro effects of these drugs on the growth of common infective agents in intensive care units were evaluated. METHODS: For detection of contamination risk, drugs were prepared ready to use under intensive care unit conditions, were tested. Effects of these three drugs on bacterial growth were also investigated. Drugs were prepared at the concentrations used in the intensive care unit and inoculated with common pathogens after which they were incubated at 4ºC, 22ºC and 36ºC. Subcultures were made at 0, 2, 4 and 8 h and colony counts were evaluated. Minimum inhibitory concentration values were determined for all drugs at 4ºC, 22ºC and 36ºC. RESULTS: o growth was observed in the drugs prepared in the intensive care unit. Propofol tended to support while remifentanil inhibited bacterial growth. Effect of pantoprozole differed according to the bacteria tested. None of the drugs showed antibacterial activity at the maximum concentrations which may be achieved in blood of the patients. CONCLUSION: Propofol strongly supports the growth of the microorganisms tested, although remifentanil and pantoprazole do not. Therefore, it is important to follow the strict aseptic techniques for the preparation of propofol.

EXPERIENCIA Y OBJETIVOS: Fueron evaluados los riesgos de la contaminación de propofol al 2%, remifentanilo y pantoprazol y los efectos de esos agentes in vitro en el crecimiento de agentes infecciosos comunes en las unidades de cuidados intensivos. MÉTODOS: Para la detección del riesgo de contaminación, fueron testados agentes preparados para el uso inmediato bajo condiciones de la unidad de cuidados intensivos. También se investigaron los efectos de esos tres agentes en el crecimiento bacteriano. Los agentes fueron preparados en las concentraciones utilizadas en la unidad de cuidados intensivos e inoculados con patógenos comunes; enseguida fueron incubados a 4ºC, 22ºC y 36ºC. Fueron obtenidos subcultivos a 0, 2, 4 y 8 h y se evaluaron los conteos de las colonias. Fueron determinados los valores de concentración inhibitoria mínima para todos los agentes a 4ºC, 22ºC y 36ºC. RESULTADOS: No se observó el crecimiento en los agentes preparados en la unidad de cuidados intensivos. El Propofol soportó el crecimiento, mientras que el remifentanilo inhibió el crecimiento bacteriano. El efecto de pantoprazol varió dependiendo de la bacteria testada. Ninguno de los agentes demostró actividad antibacteriana en las concentraciones máximas que pueden ser alcanzadas en la sangre de los pacientes. CONCLUSIONES: El Propofol sustenta vigorosamente el crecimiento de los microrganismos testados, lo que no ocurre con el remifentanilo y el pantoprazol. Por tanto, es importante que se practiquen técnicas asépticas rígidas en la preparación del propofol.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Comparison of the effects of remifentanil and alfentanil on intraocular pressure in cataract surgery

Anesthesia for ophthalmic surgery requires management of intraocular pressure [IOP] during perioperative period. In an open eye, in conditions such as after traumatic injury or during cataract surgery, IOP increase can lead to permanent vision loss. Administration of narcotics concomitant with anesthetics has the ability to reduce this increase of IOP. This clinical trial aims to compare the efficacy of remifentanil and alfentanil in preventing an increase in IOP after administration of succinylcholine, intubation and during anesthesia. This double-blind clinical trial was conducted on 50 patients undergoing elective general surgery for cataracts. Patients were randomly divided into two groups. Alfentanil [20 microg/kg in 30 s] for group 1 and remifentanil [1 microg/kg in 30 s] for group 2 were injected before induction of anesthesia, and 0.5 microg/kg/min alfentanil for group 1 and 0.1 microg/kg/min remifentanil for group 2 were infused during the anesthesia. Systolic and diastolic blood pressure, heart rate, and IOP from normal eye were measured before the induction, after administration of thiopental and succinylcholine, after tracheal intubation, and 2 min later, and were repeated in 2-min intervals until the end of operation. IOP decreased after injection of anesthetics and remained lower all through the operation in both groups, but IOP decreased after injection of succinylcholine in remifentanil group while it increased in alfentanil group [P<0.05]. Results of this study indicate benefits of both remifentanil and alfentanil in managing IOP after induction and during anesthesia. It seems that remifentanil is better than alfentanil in controlling the IOP after injection of succinylcholine

Influência da anestesia venosa total, entropia e laparoscopia sobre o estresse oxidativo / Influence of total intravenous anesthesia, entropy and laparoscopy on oxidative stress / Influencia de la anestesia venosa total, entropía y laparoscopia sobre el estrés oxidativo

JUSTIFICATIVA E OBJETIVOS: Estudos recentes correlacionam mortalidade pós-operatória e anestésica, especialmente a profundidade anestésica e pressão arterial sistólica (PAS). O objetivo deste estudo foi avaliar os efeitos da profundidade da anestesia venosa total (AVT) realizada com remifentanil e propofol com monitoração da entropia de resposta (RE) sobre as concentrações sanguíneas dos marcadores do estresse oxidativo: TBARS e glutationa, durante operações pelo acesso vídeolaparoscópico. MÉTODO: Vinte pacientes adultas, ASA I, IMC 20-26 kg.m-2, idades entre 20 e 40 anos, foram aleatoriamente distribuidas em dois grupos iguais: Grupo I - submetidas a procedimento anestésico-cirúrgico com RE mantida entre 45 e 59 e Grupo II - submetidas a procedimento anestésico-cirúrgico com RE entre 30 e 44. Em ambos os grupos, a infusão de remifentanil e propofol foi controlada pelo sitio efetor (Se), ajustados para manter RE nos valores desejados (Grupos I e II) e avaliando-se sempre a taxa de supressão (TS). As pacientes foram avaliadas em seis momentos: M1(imediatamente antes da indução anestésica), M2 (antes da intubação traqueal [IT]), M3 (5 minutos após IT), M4 (imediatamente antes do pneumoperitônio-PPT), M5 (1 minuto após o PPT) e M6 (uma hora após a operação). Em todos os momentos foram avaliados os seguintes parâmetros: PAS, PAD, FC, RE, TS, TBARS e glutationa. RESULTADOS: Observaram-se aumentos no TBARS e glutationa em M5, tanto no Grupo I como no Grupo II (p < 0,05), com maiores valores no Grupo II. TS em três pacientes no Grupo II, imediatamente após PPT. CONCLUSÕES: A elevação dos marcadores no Grupo I (em M5) sugere aumento do metabolismo anaeróbico (MA) na circulação esplâncnica enquanto os valores mais elevados observados no Grupo II (GII > GI em M5 - p < 0,05%) sugerem interferência de mais um fator (anestesia profunda), como responsável pelo aumento no MA, provavelmente como resultados de maior depressão do sistema nervoso autônomo e menor autorregulação esplâncnica.

BACKGROUND AND OBJECTIVES: Recent studies have correlated postoperative mortality with anesthetic mortality, especially with the depth of anesthesia and systolic blood pressure (SBP). The aim of this study is to evaluate the effects of the depth of total intravenous anesthesia (TIVA) using remifentanil and propofol, performed with monitoring of response entropy (RE) on blood concentrations of oxidative stress markers (TBARS and glutathione) during laparoscopic operations. METHOD: Twenty adult patients, ASA I, BMI 20-26 kg.m-2, aged 20 to 40 years, were randomly distributed into two groups: Group I underwent anesthetic-surgical procedure with RE maintained between 45 and 59, and Group II underwent anesthetic-surgical procedure with RE between 30 and 44. In both groups, the remifentanil and propofol infusion was controlled by the effector site (Es), adjusted to maintain RE desired values (Groups I and II) and always assessing the suppression rate (SR). Patients were evaluated in six periods: M1 (immediately before anesthesia), M2 (before tracheal intubation [TI]), M3 (5-minutes after TI), M4 (immediately before pneumoperitoneum [PPT]), M5 (1-minute after PPT), and M6 (1-hour after the operation). The following parameters were assessed at all times: SBP, DBP, HR, RE, SR, TBARS, and glutathione. RESULTS: We found increases in TBARS and glutathione in M5, both in Group I and Group II (p < 0.05), with higher values in Group II, and SR in three patients in Group II, immediately after PPT. CONCLUSIONS: Increased markers in Group I (M5) suggests an increase in anaerobic metabolism (AM) in the splanchnic circulation while the highest values seen in Group II (GII > GI in M5, p < 0.05%) suggest interference of another factor (deep anesthesia) responsible for the increase in AM, probably as a result of increased autonomic nervous system depression and minor splanchnic self-regulation.

JUSTIFICATIVA Y OBJETIVOS: Estudios recientes correlacionan la mortalidad postoperatoria y anestésica, especialmente con la profundidad anestésica y con la presión arterial sistólica (PAS). El objetivo de este estudio, fue evaluar los efectos de la profundidad de la anestesia venosa total (AVT) realizada con el remifentanil y el propofol, con la monitorización de la entropía de respuesta (RE) sobre las concentraciones sanguíneas de los marcadores del estrés oxidativo: TBARS y glutationa, durante operaciones por el acceso videolaparoscópico. MÉTODO: Veinte pacientes adultas, ASA I, IMC 20 y 26 kg.m-2, con edades entre 20 y 40 años, fueron aleatoriamente distribuidas en dos grupos iguales: Grupo I - sometidas a un procedimiento anestésico-quirúrgico con RE mantenida entre 45 y 59, y el Grupo II - sometidas a un procedimiento anestésico-quirúrgico con RE entre 30 y 44. En los dos grupos, la infusión de remifentanil y propofol fue controlada por el sitio efector (Se), ajustados para mantener RE dentro de los valores deseados (Grupos I y II) y evaluando siempre la tasa de supresión (TS). Las pacientes fueron evaluadas en seis momentos: M1 (inmediatamente antes de la inducción anestésica), M2 (antes de la intubación traqueal [IT]), M3 (5 minutos después de la IT), M4 (inmediatamente antes del pneumoperitoneo - PPT), M5 (1 minuto después del PPT) y M6 (una hora después de la operación). En todos los momentos fueron evaluados los siguientes parámetros: PAS, PAD, FC, RE, TS, TBARS y glutationa. RESULTADOS: Fueron observados aumentos en el TBARS y glutationa en M5, tanto en el Grupo I como en el Grupo II (p < 0,05), con mayores valores en el Grupo II. Y la TS en tres pacientes en el Grupo II, inmediatamente después del PPT. CONCLUSIONES: La elevación de los marcadores en el Grupo I (en M5) nos sugiere un aumento del metabolismo anaeróbico (MA) en la circulación espláncnica, mientras que los valores más elevados observados en el Grupo II (GII > GI en M5 - p < 0,05%) sugieren una interferencia de otro factor (anestesia profunda), como siendo la responsable del aumento en el MA, tal vez como resultado de una mayor depresión del sistema nervioso autónomo y una menor autorregulación espláncnica.

Remifentanil in critically ill cardiac patients.

Remifentanil has a unique pharmacokinetic profile, with a rapid onset and offset of action and a plasmatic metabolism. Its use can be recommended even in patients with renal impairment, hepatic dysfunction or poor cardiovascular function. A potential protective cardiac preconditioning effect has been suggested. Drug-related adverse effects seem to be comparable with other opioids. In cardiac surgery, many randomized controlled trials demonstrated that the potential benefits of the use of remifentanil not only include a profound protection against intraoperative stressful stimuli, but also rapid postoperative recovery, early weaning from mechanical ventilation, and extubation. Remifentanil shows ideal properties of sedative agents being often employed for minimally invasive cardiologic techniques, such as transcatheter aortic valve implantation and radio frequency treatment of atrial flutter, or diagnostic procedures such as transesophageal echocardiography. In intensive care units remifentanil is associated with a reduction in the time to tracheal extubation after cessation of the continuous infusion; other advantages could be more evident in patients with organ dysfunction. Effective and safe analgesia can be provided in case of short and painful procedures (i.e. chest drain removal). In conclusion, thanks to its peculiar properties, remifentanil will probably play a major role in critically ill cardiac patients.

The Effects of a Single Bolus of Remifentanil on Corrected QT Interval Change during Sevoflurane Induction

PURPOSE: Opioids may affect changes in the corrected QT interval (QTc) during anesthetic induction. This study examine whether a single bolus of remifentanil would prolong QTc after laryngeal mask airway (LMA) insertion during sevoflurane induction. MATERIALS AND METHODS: Forty women of American Society of Anesthesiologists physical status 1 (ASA PS1) undergoing gynecological surgery were studied. All patients were induced using three vital capacity inhalation inductions with 5% sevoflurane. Two minutes after induction, the inspiratory concentration of sevoflurane was reduced to 2%. Using double-blinded randomization, patients were allocated into one of two groups, receiving either saline (placebo group, n = 20) or 0.25 microg.kg-1 remifentanil (remifentanil group, n = 20) over a period of thirty seconds. Sixty seconds later, LMA insertion was performed. Recordings were taken with a 12-lead electrocardiogram at baseline, 2 min after induction and 1 and 3 min after LMA insertion. QTc was calculated by Bazett's formula. The mean arterial pressure (MAP) and heart rate (HR) were also measured at each time point. RESULTS: The QTc interval was significantly prolonged in the placebo group as compared to the remifentanil group at 1 min after LMA insertion (467.8 +/- 16.5 vs. 442.7 +/- 21.3 ms, p < 0.001). However, there was no significant difference in QTc at 3 min after LMA insertion between the two groups. MAP and HR were significantly higher in the placebo group (p < 0.001). CONCLUSION: A single bolus of remifentanil is safe method to attenuate prolonged QTc associated with insertion of LMA.

[ effect of a single dose of gabapentin on the rate of consumption of propofol and remifentanil during total intravenous anesthesia]

Gabapentin [structural analog of GABA], is an antiepileptic drug that its preoperative administration results in postoperative pain reduction. Considering the hypnotic effect of propofol, which is mediated by its attachment to GABAA, this hypothesis was propounded that administration of gabapentin can probably decrease the need for propofol and remifentanil during total intravenous anesthesia. Fifty patients scheduled for elective laparoscopic cholecystectomy, were assigned into two equal groups [n=25] in this randomized double blinded clinical trial. Study group received oral gabapentin [1200mg], and control group received placebo 3hrs before operation. Premedication and induction of anesthesia were the same in all patients. For the maintenance of anesthesia, oxygen and nitrous oxide [50%-50% mixture] and propofol and remifentanil infusion were used. The rate of propofol infusion was adjusted to maintain BIS in the range of 40- 60, and dose of remifentanil adjusted to maintain hemodynamic variables in the range of +/- 20% of baseline values. At the end of anesthesia the duration of anesthesia and the total amount of propofol and remifentanil used for every patient were recorded. The demographic parameters were similar in both groups [p>0.05]. Doses of propofol and remifentanil used for study group were significantly lower than doses used for control group [p<0.01]. The mean values of baseline systolic, diastolic, mean arterial, heart rates and BIS in the study group were lower than the corresponding values in the control group [p<0.05]. This study showed that a single dose of gabapentin before operation can decrease the need for propofol and remifentanil in total intravenous anesthesia during laparoscopic cholecystectomy

Synthesis of some novel analogues of 4-[l-pyrrolidinyl] piperidine and their effect on plasma glucose level

In the present study some compounds of 4-[1-Pyrrolidinyl] Piperidine [I] have been synthesized. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques. All the derivatives [II, III, IV and V] and the parent compound [I] at the dose of 100 mg/kg were evaluated for their effect on plasma glucose level. Compound [II] was the only derivative which showed effect on plasma glucose level

Comparison of rimonabant and sibutramine treatment effects on food compulsion in rats / Comparação do efeito do rimonabanto e da sibutramina no tratamento da compulsão alimentar em ratos

PURPOSE: To compare the therapeutic effect of rimonabant, a new drug which is a selective antagonist of CB1 receptors, with the sibutramine. METHODS: It is an experimental clinical trial, prospective, placebo controlled. Our test was performed in 38 rats, adults females with a hyper caloric diet. We collected their blood 3 times and weighted them once a week. We divided the rats in 3 groups: Rimonabant, Sibutramine and Control. Statistic analysis has been made through ANOVA test, Tukey test and t Student test. RESULTS: The Rimonabant group demonstrated a significant reduction of the weight increase in rats. The Sibutramine group showed a significant reduction on blood glycemia compared to Rimonabant group and Control group. CONCLUSIONS: Rimonabant showed to be more effective than Sibutramine by decreasing weight gain. Sibutramine has been more effective than Rimonabant and Control groups by decreasing the blood glycemia.

OBJETIVO: Comparar o efeito do rimonabanto, nova droga seletivamente antagonista dos receptores CB1, com a sibutramina. MÉTODOS: Ensaio clínico experimental, prospectivo, placebo controlado. Realizado com 38 ratas, adultas, submetidas a dieta hipercalórica. Foram coletadas 3 amostras de sangue e o peso controlado semanalmente. Foram divididas em 3 grupos: Rimonabanto, Sibutramina e Controle. Analise estatística realizada com ANOVA, teste t de Student e teste de Tukey. RESULTADOS: O grupo Rimonabanto obteve redução significante do ganho de peso. O grupo Sibutramina teve redução significativa da glicemia quando comparado aos demais grupos. CONCLUSÕES: Rimonabanto foi mais efetivo que a Sibutramina na redução do ganho de peso. A Sibutramina foi mais efetiva na redução da glicemia do que os grupos controle e Rimonabanto.

L-histidine enhances learning in stressed zebrafish

The aim of the present study was to determine the effect of the histaminergic precursor L-histidine and the H3 receptor antagonist thioperamide on the learning process of zebrafish submitted or not to confinement stress. On each of the 5 consecutive days of experiment (D1, D2, D3, D4, D5), animals had to associate an interruption of the aquarium air supply with food offering. Non-stressed zebrafish received an intraperitoneal injection of 100 mg/kg L-histidine, 10 mg/kg thioperamide or saline after training. Stressed animals received drug treatment and then were submitted to confinement stress for 1 h before the learning procedure. Time to approach the feeder was measured (in seconds) and was considered to be indicative of learning. A decrease in time to approach the feeder was observed in the saline-treated group (D1 = 141.92 ± 13.57; D3 = 55 ± 13.54), indicating learning. A delay in learning of stressed animals treated with saline was observed (D1 = 217.5 ± 25.66). L-histidine facilitated learning in stressed (D1 = 118.68 ± 13.9; D2 = 45.88 ± 8.2) and non-stressed (D1 = 151.11 ± 19.20; D5 = 62 ± 14.68) animals. Thioperamide inhibited learning in non-stressed (D1 = 110.38 ± 9.49; D4 = 58.79 ± 16.83) and stressed animals (D1 = 167.3 ± 26.39; D5 = 172.15 ± 27.35). L-histidine prevented the increase in blood glucose after one session of confinement (L-histidine = 65.88 ± 4.50; control = 53 ± 3.50 mg/dL). These results suggest that the histaminergic system enhances learning and modulates stress responses in zebrafish.

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an Índex of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 ± 4.8 percent, 92.3 percent ± 22.8 percent of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.