Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort.

BACKGROUND: Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. AIM: To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. METHODS: This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. RESULTS: Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. CONCLUSION: In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Does RAS Status Increase the Prevalence of Positive Resection Margin in Colorectal Liver Metastasis? A Systematic Review and Meta-Analysis.

BACKGROUND: Colorectal liver metastasis has a high incidence, and RAS oncogene mutation status carries significant prognostic information. We aimed to assess whether RAS-mutated patients present more or less frequently with positive margins in their hepatic metastasectomy. METHODS: We performed a systematic review and meta-analysis of studies from PubMed, Embase, and Lilacs databases. We analyzed liver metastatic colorectal cancer studies, which included information on RAS status and had surgical margin analysis of the liver metastasis. Odds ratios were computed using a random-effect model due to anticipated heterogeneity. We further performed a subanalysis limited to studies that included only patients with KRAS instead of all-RAS mutations. RESULTS: From the 2,705 studies screened, 19 articles were included in the meta-analysis. There were 7,391 patients. The prevalence of positive resection margin was not significantly different between patients carrier vs non-carrier for the all-RAS mutations (OR .99; 95% CI 0.83-1.18; P = .87), and for only KRAS mutation (OR .93; 95% CI 0.73-1.19; P = .57). CONCLUSIONS: Despite the strong correlation between colorectal liver metastasis prognosis and RAS mutation status, our meta-analysis's results suggest no correlation between the RAS status and the prevalence of positive resection margins. The findings contribute to a better understanding of the RAS mutation's role in the surgical resections of colorectal liver metastasis.

Liver volumetric and anatomic assessment in living donor liver transplantation: The role of modern imaging and artificial intelligence.

The shortage of deceased donor organs has prompted the development of alternative liver grafts for transplantation. Living-donor liver transplantation (LDLT) has emerged as a viable option, expanding the donor pool and enabling timely transplantation with favorable graft function and improved long-term outcomes. An accurate evaluation of the donor liver's volumetry (LV) and anatomical study is crucial to ensure adequate future liver remnant, graft volume and precise liver resection. Thus, ensuring donor safety and an appropriate graft-to-recipient weight ratio. Manual LV (MLV) using computed tomography has traditionally been considered the gold standard for assessing liver volume. However, the method has been limited by cost, subjectivity, and variability. Automated LV techniques employing advanced segmentation algorithms offer improved reproducibility, reduced variability, and enhanced efficiency compared to manual measurements. However, the accuracy of automated LV requires further investigation. The study provides a comprehensive review of traditional and emerging LV methods, including semi-automated image processing, automated LV techniques, and machine learning-based approaches. Additionally, the study discusses the respective strengths and weaknesses of each of the aforementioned techniques. The use of artificial intelligence (AI) technologies, including machine learning and deep learning, is expected to become a routine part of surgical planning in the near future. The implementation of AI is expected to enable faster and more accurate image study interpretations, improve workflow efficiency, and enhance the safety, speed, and cost-effectiveness of the procedures. Accurate preoperative assessment of the liver plays a crucial role in ensuring safe donor selection and improved outcomes in LDLT. MLV has inherent limitations that have led to the adoption of semi-automated and automated software solutions. Moreover, AI has tremendous potential for LV and segmentation; however, its widespread use is hindered by cost and availability. Therefore, the integration of multiple specialties is necessary to embrace technology and explore its possibilities, ranging from patient counseling to intraoperative decision-making through automation and AI.

Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

Lippia origanoides essential oil induces tocolytic effect in virgin rat uterus and inhibits writhing in a dysmenorrhea mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Lippia origanoides Kunth, popularly known as "salva-de-marajó", is used in Brazilian traditional "quilombola" communities to treat menstrual cramps and uterine inflammation. AIM OF THE STUDY: Evaluate the spasmolytic activity of Lippia origanoides essential oil (LOO) on experimental models of uterine conditions related to menstrual cramps and investigate its mechanism of action. MATERIALS AND METHODS: Virgin rat-isolated uterus was mounted in the organ bath apparatus to evaluate the spasmolytic effect of LOO on basal tonus and contractions induced by carbachol, KCl, or oxytocin. We used pharmacological agents to verify the relaxation mechanism of LOO. The evaluation of uterine contractility in virgin rats, after treatment with LOO for three consecutive days, was carried out by the construction of a concentration-response curve with oxytocin or carbachol. The primary dysmenorrhea animal model was replicated with an injection of estradiol cypionate in female mice for three consecutive days, followed by intraperitoneal application of oxytocin. RESULTS: LOO relaxed the rat uterus precontracted with 10-2 IU/mL oxytocin (logEC50 = 1.98 ± 0.07), 1 µM carbachol (logEC50 = 1.42 ± 0.07) or 60 mM KCl (logEC50 = 1.53 ± 0.05). It was also able relax uterus on spontaneous contractions (logEC50 = 0.41 ± 0.05). Preincubation with glibenclamide, propranolol, phentolamine or L-NAME in contractions induced by carbachol did not alter significantly the relaxing effect of LOO. However, in the presence of 4-aminopyridine, CsCl or tetraethylammonium there was a reduction of LOO potency, whereas the blockers methylene blue, ODQ, aminophylline and heparin potentiated the LOO relaxing effect. Preincubation with LOO in a Ca2+ free medium at concentrations of 27 µg/mL or 81 µg/mL reduced the contraction induced by carbachol. The administration of LOO for 3 days did not alter uterus contractility. The treatment with LOO at 30 or 100 mg/kg intraperitoneally, or 100 mg/kg orally, inhibited writhing in female mice. The association of LOO at 10 mg/kg with nifedipine or mefenamic acid potentiated writhing inhibition in mice. CONCLUSIONS: The essential oil of L. origanoides has tocolytic activity in rat isolated uterus pre-contracted with KCl, oxytocin, or carbachol. This effect is possibly related to the opening of potassium channels (Kir, KV, and KCa), cAMP increase, and diminution of intracellular Ca2+. This relaxant effect, probably, contributed to reduce the number of writhings in an animal model of dysmenorrhea being potentiated by nifedipine or mefenamic acid. Taken together, the results here presented indicate that this species has a pharmacological potential for the treatment of primary dysmenorrhea, supporting its use in folk medicine.

Surgical resection for non-Asian intrahepatic lithiasis: The Brazilian experience.

BACKGROUND: Intrahepatic lithiasis (IHL) is a rare disease in the western world. Complications associated with IHL include acute cholangitis, liver atrophy, secondary biliary cirrhosis, and risk for intrahepatic cholangiocarcinoma. Liver resection is considered the treatment of choice for IHL. The objective of this study was to analyze patients who underwent liver resection for non-Asian hepatolithiasis. METHODS: 127 patients with symptomatic non-Asian hepatolithiasis underwent resection in six institutions. Demographic data, clinical presentation, diagnosis, classification according to stone location, presence of atrophy, bile duct stricture, biliary cirrhosis, incidence of cholangiocarcinoma, treatment and postoperative course were evaluated. RESULTS: 52 patients (40.9%) were male and the mean age was 46.1 years. Sixty-six patients (51.9%) presented with history of cholangitis. Stones were located in the left lobe in 63 (49.6%), and right lobe in 28 patients (22.0%). Atrophy was observed in 31 patients (24.4%) and biliary stenosis in 18 patients (14.1%). The most common procedure performed was left lateral sectionectomy in 63 (49.6%) patients, followed by left hepatectomy in 36 (28.3%), right hepatectomy in 19 (15.0%), and associated hepaticojejunostomy in 28 (22.0%). Forty-two patients (33.0%) presented postoperative complications and the most common were biliary fistula (13.3%) and surgical site infection (7.0%). Postoperative mortality was 0.7%. Intrahepatic cholangiocarcinoma was observed in 2 patients (1.5%). Recurrence was identified in 10 patients (7.8%), mostly with bilateral stones and/or hepaticojejunostomy. CONCLUSION: Liver resection is the standard treatment for symptomatic unilateral or complicated IHL with good operative results. Risk of cholangiocarcinoma was low in non-Asian patients.

Essential oils in the management of soft rot of kale in the brazilian semiarid region / Óleos essenciais no manejo da podridão mole em couve no semiárido brasileiro

The aim of this study was to analyze the effect of essential oils on the control of soft rot of kale. Clove essential oil at 0.25%, lemongrass and palmarosa essential oils at 0.5%, melaleuca and orange essential oils at 0.75%, bergamot, rosemary, sage and ginger essential oils at 1% were evaluated for the in vitro inhibition of Pectobacterium carotovorum subsp. brasiliensis (Pcb) and control of soft rot of kale, sprayed 72 hours before or seven hours after inoculation. Clove, citronella, bergamot, rosemary, palmarosa, sage, melaleuca, and lemongrass oils completely inhibited the growth of Pcb. Lemongrass oil (0.5%) caused 0% of disease incidence (INC), providing 100% of disease control in both periods of inoculation. Clove oil (0.25%) showed a lower INC (25%) when applied after inoculation, providing a control percentage of 71.42%. The lemongrass and clove essential oils were analyzed by GC/FID (Gas Chromatography ­ Flame Ionization Detector) and by GC/MS (Gas Chromatography /Mass Spectrometer). The major components were eugenol (91,9%) for clove oil and citral, isometric mixture of neral (34,1%) and geranial (42,9%) for lemongrass oil. The Minimum inhibitory concentration (MIC) of lemongrass, clove oils and their major components (citral and eugenol, respectively) was determined by using a broth macrodilution technique, as well as they were evaluated at different concentrations on the control of soft rot of kale, sprayed according descriptions above. The MIC was 0.03125% for citral, and 0.0625 and 0.125% for lemongrass and clove oils, respectively. Eugenol didn't show MIC. Lemongrass oil at 0.125% (post-inoculation) and citral at 0.125% (pre and post-inoculation) provided the highest percentages of disease control (33.33, 50, and 100%, respectively). Clove oil at 0.125% (post-inoculation) showed better effectiveness than eugenol (0.25%), providing a percentage of disease control of 16.67%. Lemongrass and clove essential oils were the most effective in control of soft rot of kale, suggesting that these oils have a potential to be used as antibacterial agents.

O objetivo do estudo foi avaliar o efeito de óleos essenciais no controle da podridão mole em couve. Os óleos essenciais de cravo a 0,25%, capim-limão e palmarosa a 0,5%, citronela, melaleuca e laranja a 0,75%, bergamota, alecrim, sálvia e gengibre a 1% foram avaliados na inibição in vitro de Pectobacterium carotovorum subsp. brasiliensis (Pcb) e controle da podridão mole em couve, pulverizados 72 horas antes ou sete horas após a inoculação. Os óleos essenciais de cravo, citronela, bergamota, alecrim, palmarosa, sálvia, melaleuca e capim-limão inibiram completamente o crescimento de Pcb. O óleo de capimlimão (0,5%) promoveu 0% de incidência (INC) da doença (percentual de controle de 100%), em ambos os períodos de inoculação. O óleo de cravo (0,25%) proporcionou menor INC (25%) quando aplicado após inoculação (percentual de controle de 71,42%). Os óleos essenciais de capim-limão e cravo foram analisados por GC/FID (cromatografia gasosa/detector por ionização de chama) e por GC/MS (cromatografia gasosa/ espectometria de massas). Os componentes majoritários foram eugenol (91,9%) no óleo de cravo e citral (neral34,1% e geranial- 42,9%) no óleo de capim-limão. A concentração inibitória mínima (CIM) dos óleos essenciais de capim-limão e cravo e de seus componentes majoritários (citral e eugenol, respectivamente) foi determinada por meio da técnica de macrodiluição em caldo, bem como foram avaliados, em diferentes concentrações, no controle da podridão mole em couve, pulverizados conforme descrito acima. A concentração inibitória mínima (CIM) foi de 0,03125% para o citral, e de 0,0625 e 0,125% para os óleos de capim-limão e cravo, respectivamente. O eugenol não apresentou CIM. O óleo de capim-limão a 0,125% (pós-inoculação) e o citral (0,125%), em ambos os períodos de inoculação, proporcionaram os maiores percentuais de controle (33,33; 50 e 100%, respectivamente). O óleo de cravo a 0,125% (pós-inoculação) mostrou maior eficiência que o eugenol (0,25%), promovendo um percentual de controle de 16,67%. Os óleos essenciais de capim-limão e cravo destacaram-se na eficiência de controle da podridão mole em couve, sugerindo que esses óleos têm potencial para serem utilizados como agentes antibacterianos.

Lippia alnifolia essential oil induces relaxation on Guinea-pig trachea by multiple pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia alnifolia Mart. & Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro" and "pedrécio", is used in folk medicine as antiseptic and to treat diseases that affect respiratory system, like bronchitis and asthma. AIM OF THE STUDY: The aim of this work was to investigate the spasmolytic activity and relaxant mechanism of the Lippia alnifolia essential oil (EOLA) on isolated guinea-pig trachea and to correlate with its use in folk medicine. MATERIALS AND METHODS: Leaves from L. alnifolia were collected in Pico das Almas, Chapada Diamantina, situated in the city of Rio de Contas, Bahia, Brazil. EOLA was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity was assayed in isolated guinea-pig trachea pre-contracted with carbachol 1 µM or histamine 10 µM. Relaxant mechanism of EOLA was determined comparing concentration-response curves in the presence or absence of different blockers. RESULTS: Chemical analysis revealed the presence of carvone (60 ±â€¯0.8%) as major constituent. EOLA (1-243 µg/mL) relaxed isolated guinea-pig trachea pre-contracted with carbachol 1 µM [EC50 = 53.36 (44.75-63.51) µg/mL] or histamine 10 µM [EC50 = 5.42 (4.42-6.65) µg/mL]. The pre-incubation of 4-aminopyridine in histamine-induced contractions did not alter significantly the relaxant effect of EOLA. However, the presence of cesium chloride, glibenclamide, tetraethylammonium, propranolol, indomethacin, dexamethasone, hexamethonium, atropine, L-NAME, methylene blue or ODQ reduced EOLA relaxant effect. EOLA 18 µg/mL pre-incubation in calcium-free medium reduced histamine-evoked contractions, but did not alter histamine contractions in the presence of nifedipine. CONCLUSIONS: Lippia alnifolia essential oil has spasmolytic activity on isolated guinea-pig trachea and its mechanism of action possibly involves the activation of multiple signal transduction pathways, which culminate in potassium channels activation and cytosolic calcium reduction.

LIVER RESECTION FOR NON-ORIENTAL HEPATOLITHIASIS.

BACKGROUND: Primary intrahepatic lithiasis is defined when the stones are formed in the liver and associated with local dilatation and biliary stricture. Liver resection is the ideal procedure. AIM: To evaluate the results of liver resection in the treatment of non-oriental intrahepatic lithiasis. METHODS: Fifty-one patients with symptomatic benign non-oriental hepatolithiasis underwent surgical resection in six institutions in Brazil. Demography data, clinical symptoms, classification, diagnosis, management and postoperative course were analyzed. RESULTS: Of the 51 patients, 28 were male (54.9%), with a mean age of 49.3 years. History of cholangitis was observed in 15 (29.4%). The types of intrahepatic lithiasis were type I in 39 (76.5%) and type IIb in 12 (23.5%), with additional type Ea in six (11.8%). Liver function test were normal in 42 patients (82.4%). Segmental atrophy was observed in 12 (23.5%). Treatments included left lateral sectionectomy in 24 (47.1%), left hepatectomy in 14 (27.5%) and right hepatectomy in eight (15.7%), with associated hepaticojejunostomy in four (7.8%). Laparoscopic liver resection was performed in eight (15.7%). Postoperative complications were observed in 20 (39.2%) with no mortality. CONCLUSION: Liver resection in patients with hepatolithiasis is the ideal procedure as it removes stones, stricture, atrophic parenchyma, and minimizes the risk of cholangiocarcinoma.

Spasmolytic and antidiarrheal activities of Lippia thymoides (Verbenaceae) essential oil.

Lippia thymoides ('alecrim-do-mato' or 'alecrim-do-campo') is used in Brazilian folk medicine to treat various illnesses, including diarrhea. This work aimed to evaluate in vitro spasmolytic and in vivo antidiarrheal activities of the L. thymoides essential oil (OOS) and to correlate with the traditional use of this plant. In isolated guinea-pig ileum, OOS presented a concentration-dependent spasmolytic activity in preparations pre-contracted with KCl 40 mM [EC50 = 16.89 (11.56-24.66) µg/mL], and antagonized phasic contractions induced by 1 µM carbachol [IC50 = 42.71 (37.35-48.83) µg/mL] or histamine [IC50 = 32.38 (27.44-38.20) µg/mL]. In mice, OOS at 400 mg/kg reduced intestinal transit, at 200 and 400 mg/kg reduced total stool mass and at 400 mg/kg reduced intestinal fluid accumulation. It was shown that the antidiarrheal effect of OOS is related to the inhibition of smooth muscle contraction and may be due to the presence of major compound ß-caryophyllene in this essential oil.

Liver resection for non-oriental hepatolithiasis / Ressecção hepática no tratamento da hepatolitíase não oriental

ABSTRACT Background: Primary intrahepatic lithiasis is defined when the stones are formed in the liver and associated with local dilatation and biliary stricture. Liver resection is the ideal procedure. Aim: To evaluate the results of liver resection in the treatment of non-oriental intrahepatic lithiasis. Methods: Fifty-one patients with symptomatic benign non-oriental hepatolithiasis underwent surgical resection in six institutions in Brazil. Demography data, clinical symptoms, classification, diagnosis, management and postoperative course were analyzed. Results: Of the 51 patients, 28 were male (54.9%), with a mean age of 49.3 years. History of cholangitis was observed in 15 (29.4%). The types of intrahepatic lithiasis were type I in 39 (76.5%) and type IIb in 12 (23.5%), with additional type Ea in six (11.8%). Liver function test were normal in 42 patients (82.4%). Segmental atrophy was observed in 12 (23.5%). Treatments included left lateral sectionectomy in 24 (47.1%), left hepatectomy in 14 (27.5%) and right hepatectomy in eight (15.7%), with associated hepaticojejunostomy in four (7.8%). Laparoscopic liver resection was performed in eight (15.7%). Postoperative complications were observed in 20 (39.2%) with no mortality. Conclusion: Liver resection in patients with hepatolithiasis is the ideal procedure as it removes stones, stricture, atrophic parenchyma, and minimizes the risk of cholangiocarcinoma.

RESUMO Racional: Litíase intra-hepática primária é definida quando os cálculos são formados dentro do fígado, podendo estar associada à dilatação local e estenosa da via biliar. A ressecção hepática é considerada o procedimento ideal. Objetivo: Avaliar os resultados da ressecção hepática no tratamento da litíase intra-hepática não oriental. Métodos: Cinquenta e um pacientes com hepatolitíase benigna não oriental sintomática foram submetidos à ressecção hepática em seis instituições no Brazil. Os dados demográficos, sintomas clínicos, classificação, diagnóstico, tratamento e evolução pós-operatória foram analisados. Resultados: Dos 51 pacientes havia 28 homens (54,9%), e a idade média era de 49,3 anos. História de colangite foi observada em 15 pacientes (29,4%). Os tipos de litíase observados foram tipo I em 39 (76,5%) e tipo IIb em 12 (23,5%), com o tipo adicional Ea em seis pacientes (11,8%). Os testes de função hepática estavam normais em 42 (82,4%) e atrofia segmentar foi observada em 12 (23,5%). O tratamento incluiu setorectomia lateral esquerda em 24 (47,1%), hepatectomia esquerda em 14 (27,5%) e hepatectomia direita em oito pacientes (15,7%). A hepaticojejunostomia esteve associada ao procedimento inicial em quatro (7,8%). Hepatectomia por videolaparoscopia foi realizada em oito (15,7%). Complicações pós-operatórias foram observadas em 20 pacientes (39,2%) e não houve mortalidade. Conclusão: Ressecção hepática na hepatolitíase é o procedimento ideal, pois remove os cálculos, a estenose, o parênquima atrofiado e minimiza os riscos para colangiocarcinoma.

Relaxant effect of Lippia origanoides essential oil in guinea-pig trachea smooth muscle involves potassium channels and soluble guanylyl cyclase.

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia origanoides H.B.K. is an aromatic species used in folk medicine to treat respiratory diseases, including asthma. AIM OF THE STUDY: The aim of this work was to evaluate the relaxing potential and mechanism of action of the L. origanoides (LOO) essential oil in isolated guinea-pig trachea. MATERIALS AND METHODS: Leaves from L. origanoides were collected at experimental fields under organic cultivation, at the Forest Garden of Universidade Estadual de Feira de Santana. Essential oil was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity and relaxant mechanism of LOO were assayed in isolated guinea-pig trachea contracted with histamine, carbachol or hyperpolarizing KCl. RESULTS: Chemical analysis revealed the presence of carvacrol (53.89%) as major constituent. LOO relaxed isolated guinea-pig trachea pre-contracted with KCl 60 mM [EC50 = 30.02 µg/mL], histamine 1 µM [EC50 = 9.28 µg/mL] or carbachol 1 µM [EC50 = 51.80 µg/mL]. The pre-incubation of glibenclamide, CsCl, propranolol, indomethacin, hexamethonium, aminophylline or L-NAME in histamine-induced contractions did not alter significantly the relaxant effect of LOO. However, the presence of 4-aminopyridine, tetraethylammonium or methylene blue reduced LOO effect, while the presence of dexamethasone or atropine potentialized the LOO relaxant effect. LOO pre-incubation inhibited carbachol-evoked contractions, with this effect potentialized in the presence of sodium nitroprusside and blocked in the presence of ODQ. CONCLUSIONS: The relaxant mechanism of LOO on the tracheal smooth muscle possibly involves stimulating of soluble guanylyl cyclase with consequent activation of the voltage-gated and Ca2+-activated K+ channels.

Growth and volatile compounds of Martianthus leucocephalus exposed to heavy metal stress / Crescimento e teor de compostos voláteis de Martianthus leucocephalus submetida ao estresse por metais

ABSTRACT: Martianthus leucocephalus is found in the semi-arid Northeast of Brazil and has high pharmacological potential due to the production of volatile compounds. This study aimed to evaluate the Cd (15, 30, 45 and 60µmol L-1), Cu (30, 60, 90 and 120µmol L-1) and Zn (150, 300, 450 and 600µmol L-1) levels on the growth of this species and its volatile compounds production. Apical cuttings were placed in plastic trays containing 6.0L nutrient solution, and after rooting, they were submitted to Cd, Cu and Zn treatments for 15 days. All the metals evaluated reduced the succulence and growth of all parts of M. leucocephalus . This effect was accompanied by the increase of Cd, Cu and Zn concentrations in all plant tissues. Volatile compounds content produced by M. leucocephalus was increased only by Zn (86%).

RESUMO: Martianthus leucocephalus é encontrada no semiárido nordestino e possui potencial farmacológico atribuído à produção de compostos voláteis. Este trabalho objetivou avaliar o efeito de doses de Cd (15, 30, 45 and 60µmol L-1), Cu (30, 60, 90 and 120µmol L-1) e Zn (150, 300, 450 and 600µmol L-1) no crescimento dessa espécie e na produção de compostos voláteis. Estacas apicais foram transferidas para bandejas plásticas contendo 6,0L de solução nutritiva e, após o enraizamento, foram submetidas aos tratamentos de Cd, Cu e Zn, durante 15 dias. Todos os metais avaliados reduziram a suculência e o crescimento de todas as partes de M. leucocephalus . Este efeito foi acompanhado pelo incremento das concentrações de Cd, Cu e Zn em todos os tecidos das plantas. Também foi observado que o teor de compostos voláteis, produzido por M. leucocephalus, foi aumentado apenas pelo Zn (86%).

Growth and essential oil production by Martianthus leucocephalus grown under the edaphoclimatic conditions of Feira de Santana, Bahia, Brazil / Crescimento e produção de óleo essencial de Martianthus leucocephalus cultivada nas condições edafoclimáticas de Feira de Santana, Bahia, Brasil

ABSTRACT: The semiarid region of Brazil holds a great richness of medicinal and aromatic plants with considerable potential for pharmaceutical, food, cosmetic and biopesticide industries. Martianthus leucocephalus (Mart. Ex Benth.) J. F. B. Pastore is endemic to this region, and its essential oils contain a principle compound, isobornyl formate, which demonstrates antimicrobial activity against Bacilus cereus, Staphylococcus aureus and Candida albicans. In spite of its significant pharmacological potential, little is known about its growth. In light of the influence of seasonality on plant growth, development, and secondary metabolism, the present study evaluated the growth and essential oil content of M. leucocephalus grown and harvested during different months of the year in the edaphoclimatic conditions of Feira de Santana, Bahia State, Brazil. The experimental design was entirely randomized, with twelve harvesting periods and five replicates. The study acquired monthly data of mean temperatures, relative humidity, rainfall, irradiance, and photoperiod from the National Institute of Meteorology (INMET) and quantified the fresh and dry weights of leaves, flowers and branches, as well as leaf area, and essential oil content. The data were submitted to Spearman correlation analysis and the means were compared using the Scott-Knott test. Total leaf masses and oil contents were higher during periods with longer photoperiods and higher solar irradiance. Rainfall and relative humidity reduced plant growth and essential oil content. Higher total mean dry masses were recorded from September to January (except October), while oil content was higher in March.

RESUMO: O semiárido brasileiro apresenta grande riqueza de espécies medicinais e aromáticas, com intenso uso na indústria farmacêutica, alimentícia, de cosméticos e de biopesticidas. A espécie Martianthus leucocephalus (Mart. ex Benth.) J. F. B. Pastore é endêmica dessa região. Seu óleo essencial apresenta como composto majoritário o formiato de isobornila, com atividade antimicrobiana frente à Bacilus cereus, Staphylococcus aureus e Candida albicans. Devido à grande influência da sazonalidade sobre o crescimento e produção vegetal, sobretudo quando envolve o metabolismo secundário de plantas, o objetivo deste trabalho foi avaliar o crescimento e a produção de óleo essencial de M. leucocephalus cultivada e colhida em diferentes meses do ano, nas condições edafoclimáticas de Feira de Santana, BA. O experimento foi conduzido em delineamento inteiramente casualizado (DIC), com doze tratamentos, constituídos dos diferentes meses de colheita, com cinco repetições. Mensalmente, foram obtidos os valores médios de temperatura, umidade relativa do ar, precipitação pluviométrica, irradiância e fotoperíodo, através do Instituto Nacional de Meteorologia (INMET), quantificando-se também a massa fresca e seca das folhas, flores e caule, a área foliar e o teor de óleo essencial das plantas. Os dados foram submetidos à análise de correlação de Spearman e as médias foram comparadas pelo teste de Scott-Knott. A massa seca total e o teor de óleo aumentaram em função da irradiância e reduziram em função da precipitação pluviométrica e umidade relativa do ar. As maiores médias de massa seca total foram encontradas durante os meses de setembro a janeiro, exceto outubro, e de teor de óleo no mês de março.

Chemical composition and pharmacological properties of the essential oils obtained seasonally from Lippia thymoides.

CONTEXT: Lippia thymoides Mart. & Schauer (Verbenaceae) is used in folk medicine to treat wounds, fever, bronchitis, rheumatism, headaches, and weakness. OBJECTIVE: This study determinates the chemical composition of essential oils from L. thymoides, obtained at during each of the four seasons and correlates with pharmacological properties. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and analyzed by gas chromatography coupled to mass spectroscopy (GC-MS). Antioxidant activity was determined by DPPH free radical scavenging and ß-carotene bleaching methods. The antimicrobial assays were performed by minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) methods. Isolated rat aorta and uterus, and guinea-pig trachea were utilized to evaluate relaxant potential in pre-contracted smooth muscle. RESULTS AND DISCUSSION: Essential oils from leaves of L. thymoides had the sesquiterpene ß-caryophyllene (17.22-26.27%) as the major constituent followed by borneol (4.45-7.36%), camphor (3.22-8.61%), camphene (2.64-5.66%), and germacrene D (4.72-6.18%). In vitro assays showed that these essential oils do not have antioxidant activity, have antimicrobial selectivity to Gram-positive bacteria Staphylococcus aureus (MIC = 0.004 mg/mL and MMC = 0.26-10.19 mg/mL) and Micrococcus luteus (MIC = 0.03 mg/mL and MMC = 8.43 mg/mL), relax isolated rat aorta (EC50 = 305-544 µg/mL, with endothelium; and EC50 = 150-283 µg/mL, without endothelium), and uterus (EC50 = 74-257 µg/mL), and minor potency, isolated guinea-pig trachea. CONCLUSIONS: Lippia thymoides is a source of natural products of pharmaceutical interest, being necessary additional studies to determine the substances involved in the biological activities.

Atividade antimicrobiana do óleo essencial de Ocimum americanum e Ocimum basilicum sobre periodontopatógenos / Antimicrobial activity of essential oil of Ocimum americanum and Ocimum basilicum against periodontopathogens

Na doença periodontal, a resposta imune ao desafio microbiano resulta em ativação de osteoclastos e reabsorção do osso alveolar, culminando com a perda do dente. Deste modo, a busca por compostos com atividade antimicrobiana torna-se relevante no controle da formação do biofilme dental. Com o crescente aumento da resistência bacteriana aos antimicrobianos, o descobrimento de novas drogas seria uma ferramenta útil e neste cenário as plantas medicinais são alternativas promissoras. No presente estudo a atividade antimicrobiana de óleos essenciais extraídos de folhas e flores de Ocimum americanum e Ocimum basilicum foi avaliada frente aos periodontopatógenos Aggregatibacter actinomycetemcomitans (ATCC 43717), Fusobacterium nucleatum (ATCC 25586), Porphyromonas gingivalis (ATCC 33277) e frente ao micro-organismo Bacteroides fragilis (ATCC 25285). O método de macrodiluição em tubos foi utilizado para determinação da concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM). Foram registrados menores valores de CIM (0,00625 mg.mL-1 a 0,0125 mg.mL-1) frente a bactéria P. gingivalis, sendo os maiores valores ( <3,2 mg.mL-1) registrados para A. actinomycetemcomitans. Estas concentrações foram consideradas bactericidas quando a CBM foi avaliada. A composição química dos óleos mostrou a presença de linalol e metil cinamato, compostos com reconhecida atividade antimicrobiana, o que poderia explicar os resultados encontrados. Este trabalho mostrou que as plantas medicinais do gênero Ocimum estudadas foram capazes de inibir o crescimento microbiano, especialmente de P. gingivalis, apresentando, portanto, potencial biotecnológico para uso na área de odontologia

In Periodontal disease, the immune response to microbial challenge results in osteoclast activation and alveolar bone resorption, leading to tooth loss, so the search for chemical compounds with antimicrobial activity is relevant to control biofilm formation. With the increasing of bacterial resistance to antibiotics, the discovery of new drugs would be a useful tool, and in this scenario the medicinal plants are promising alternatives. In this study, the antimicrobial activity of essential oils extracted from leaves and flowers of Ocimum americanum and Ocimum basilicum was evaluated against the periodontopathogens Aggregatibacter actinomycetemcomitans (ATCC 43717), Fusobacterium nucleatum (ATCC 25586), Porphyromonas gingivalis (ATCC 33277) and against the bacteria Bacteroides fragilis (ATCC 25285). The macrodilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). There were recorded lower values of MIC (0.00625 mg.mL-1 to 0.0125 mg.mL-1) against P. gingivalis, and the highest values (<3,2 mg.mL-1) were recorded for A. actinomycetemcomitans. These concentrations were considered bactericidal when MBC was assessed. The chemical composition of the oils showed the presence of linalool and methyl cinnamate, compounds with proven antimicrobial activity, which could explain the results. This project showed that medicinal plants studied were able to inhibit microbial growth, especially against P. gingivalis, presenting therefore biotechnological potential for use in dentistry

Usefulness of intraoperative ultrasonography in liver resections due to colon cancer metastasis.

INTRODUCTION: Intraoperative ultrasonography (IOUS) of the liver has been used both as an aid for intraoperative anatomical definition and for the detection of new lesions. The present study aimed to evaluate the impact of IOUS and to identify factors that can predict the detection of new lesions intraoperatively. METHODS: In this observational and prospective study, with a cross-sectional design, patients with colorectal cancer metastases who underwent hepatectomy were selected. Abdominal computed tomography, magnetic resonance imaging, and positron emission tomography were the preoperative evaluation tests. All patients underwent IOUS performed by the same surgeon. The intraoperative findings were compared with the preoperative tests results. RESULTS: In total, 56 hepatectomies were evaluated. Half of the patients were men, with a mean age of 57 (30-85) years. New lesions were found intraoperatively in 12 patients (21.4% of cases) and were detected on both palpation and ultrasonography in 11 of these patients. Ultrasonography helped to revise the surgical plans by providing additional information in 35.7% of cases. On multivariate analysis, the presence of more than 4 preoperative nodules was predictive of the intraoperative occurrence of new lesions. CONCLUSIONS: IOUS remains the only way to evaluate the relationships between tumors, liver vascular structures, and bile ducts intraoperatively. Alone, IOUS was not useful for identifying new lesions intraoperatively, as all new lesions were also detected on palpation. The number of lesions diagnosed on preoperative tests influenced the probability of identifying new lesions intraoperatively. There may be additional influential factors.

Pharmacological Basis for Traditional Use of the Lippia thymoides.

The aim of this study was to evaluate crude extracts and fractions from leaves and stems of Lippia thymoides and to validate their use in folk medicine. In vitro antioxidant and antimicrobial activities and in vivo wound healing in rats, baker yeast-induced fever in young rats, and acute oral toxicity in mice assays were realized. The crude extracts and their dichloromethane and ethyl acetate fractions had potent radical-scavenging activity against the DPPH but were not effective in the ß-carotene bleaching method. The dichloromethane fraction from the leaves extract showed the broadest spectrum of activity against S. aureus, B. cereus, and C. parapsilosis. The animals treated with crude extracts showed no difference in wound healing when compared with the negative control group. The crude extract from leaves (1200 mg/kg) has equal efficacy in reducing temperature in rats with hyperpyrexia compared to dipyrone (240 mg/kg) and is better than paracetamol (150 mg/kg). In acute toxicity test, crude extract of leaves from Lippia thymoides exhibited no mortality and behavioral changes and no adverse effects in male and female mice. This work validates the popular use of Lippia thymoides for treating the wound and fever, providing a source for biologically active substances.

Essential oils and isolated compounds from Lippia alba leaves and flowers: antimicrobial activity and osteoclast apoptosis.

In the present study, essential oils extracted from the leaves and flowers of Lippia alba (Mill.) N.E.Br. (L. alba) were analyzed for their antimicrobial activity and their effects on osteoclasts. The periodontal pathogens, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans; ATCC 43717), Fusobacterium nucleatum (F. nucleatum; ATCC 25586) and Porphyromonas gingivalis (P. gingivalis); ATCC 33277) were used in antimicrobial activity assays for determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), whereas Bacteroides fragilis (B. fragilis; ATCC 25285) was used as the control microorganism. Osteoclast (OC) apoptosis was assessed by TUNEL assay and Fas receptor expression was detected by immunocytochemistry. The analysis of antimicrobial activity revealed that P. gingivalis had the lowest MIC values, whereas A. actinomycetemcomitans had the highest. L. alba essential oils were found to be toxic to human cells, although the compounds, carvone, limonene and citral, were non-toxic and induced apoptosis in the OCs. This study demonstrates that L. alba has potential biotechnological application in dentistry. In fact periodontal disease has a multifactorial etiology, and the immune response to microbial challenge leads to osteoclast activation and the resorption of the alveolar bone, resulting in tooth loss.