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.

Topical foam as a promising carrier system for active pharmaceutical ingredients: review of clinical studies.

Skin disorders are preferentially treated by topical administration of medicines or cosmetics because of the possibility of local action. However, a great concern is the delivery of topical actives with effective penetration through the stratum corneum to ensure the desired effect. Considering the search for a carrier system that allows the penetration/permeation of active pharmaceutical ingredients through this structure, searching for effective topical pharmaceutical forms is needed. Foams have been widely studied over the years due to their high capacity to favor the active to overcome the cutaneous barrier and because this form of presentation has ease of application and high acceptability by users. The objective of this review was to analyze the potential of foam as a topical pharmaceutical form for treating skin disorders, upon clinical cases reported in the literature. Foam presents technical advantages when compared to other conventional topical pharmaceutical forms due to its fast action, high tolerance, and safety, with reduction or total remission of adverse events. Regarding the patient, foam increased the rate of adherence to the treatment. Therefore, it is concluded that foam is an effective, secure, and stable topical presentation form for carrying active pharmaceutical ingredients and widely accepted by patients.

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.

Local treatment of pancreatic cancer metastases: A multicenter French study of the AGEO group.

OBJECTIVE: This study reports the efficacy and safety of local treatment of metastases of pancreatic ductal adenocarcinoma (PDAC), with a curative intent. METHODS: We retrospectively included patients with histologically proven PDAC, who underwent a local treatment for metastases between January 1, 2000 and December 31, 2017, from 11 French hospitals. Complications of local treatment were reported. Univariate Cox models were performed to identify prognosis factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: We included 52 patients treated for 68 metastases; 33 (64%) of whom had metachronous metastases. Metastatic sites treated were: 39 (57%) hepatic, 18 (27%) pulmonary and 11 (16%) others. Metastases treatments were: 45 (66%) surgery, 9 (13%) radiofrequency and 14 (21%) other procedures. The rates of severe complications and mortality were respectively 10% and 4%. The median OS and DFS after local treatment were 36.5 months and 12.7 months, respectively. Prognosis factors associated with a shorter OS were: liver metastases when compared with lung metastases (HR 4.04; 95%CI: 1.18-13.81), N2 status of primary pancreatic tumor when compared to N0-N1 (HR 9.43; 95%CI: 2.44-36.36) and synchronous metastases when compared to metachronous metastases (HR 2.34; 95%CI: 1.05-5.23). N2 status of primary pancreatic tumor was associated with a shorter DFS when compared to N0-N1 (HR 2.82; 95%CI: 1.05-7.58). CONCLUSION: In this series of highly selected patients, local treatment of metastases from PDAC is associated with prolonged survival. The rate of severe complications was low. Factors associated with shorter OS were liver metastases, N2 status and synchronous metastases.

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.

Early hepatic arterial thrombosis in liver transplantation: Systemic intravenous alteplase as a potential rescue treatment after failed surgical revascularization.

eHAT is one of the most dreaded post-LT complication. Treatment approaches include retransplantation, revascularization, or observation. Systemic thrombolytic therapy is used in pediatric patients with thromboembolic events. However, there is no previous study reporting on the use of systemic r-tPA to treat eHAT. The treatment strategies used in patients with eHAT are described, focusing on two children who failed SR and were treated with systemic heparinization plus systemic r-tPA infusion. r-tPA-RP consists of intravenous systemic infusion at a dose of 0.3 mg/kg/h during 6 hours, for 5 days. First case (3-year) was transplanted with a whole liver, and second case (6-year) received a LLS from a living donor. HAT was diagnosed by doppler US and confirmed by angioCT scan in both patients in the first day after LT. They underwent SR and were clinically stable. Re-thrombosis occurred in both patients the day after, and r-TPA-RP was started-one patient required two r-TPA-RP for HAT recurrence. They presented minor bleeding, without repercussion. Hepatic artery recanalized after 10 and 3 days in the first and second patient, respectively. Retransplant was avoided, and one developed biliary strictures, successfully managed in the follow-up. r-TPA-RP avoided retransplantation after eHAT in these cases. To our knowledge, this is the first report of the use of systemic r-TPA to treat eHAT in children. This strategy may compose an algorithm to treat eHAT that failed SR in stable 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.

Involvement of the PKA pathway and inhibition of voltage gated Ca2+ channels in antihyperalgesic activity of Lippia grata/ß-cyclodextrin.

Neuropathic pain (NP) is a difficult condition to treat because of the modest efficacy of available drugs. New treatments are required. In the study we aimed to investigate the effects of the essential oil from Lippia grata alone or complexed in ß-cyclodextrin (LG or LG-ßCD) on persistent inflammatory and neuropathic pain in a mouse model. We also investigated Ca2+ currents in rat dorsal root ganglion (DRG) neurons. Male Swiss mice were treated with LG or LG/ß-CD (24 mg/kg, i.g.) and their effect was evaluated using an acute inflammatory pleurisy model and nociception triggered by intraplantar injection of an agonist of the TRPs channels. We also tested their effect in chronic pain models: injection of Freund's Complete Adjuvant and partial sciatic nerve ligation (PSNL). In the pleurisy model, LG reduced the number of leukocytes and the levels of TNF-α and IL-1ß. It also inhibited cinnamaldehyde and menthol-induced nociceptive behavior. The pain threshold in mechanical and thermal hyperalgesia was increased and paw edema was decreased in models of inflammatory and neuropathic pain. PSNL increased inflammatory protein contents and LG and LG-ßCD restored the protein contents of TNF-α, NF-κB, and PKA, but not IL-1ß and IL-10. LG inhibited voltage gated Ca2+ channels from DRG neurons. Our results suggested that LG or LG-ßCD produce anti-hyperalgesic effect in chronic pain models through reductions in TNF-α levels and PKA, and inhibited voltage-gated calcium channels and may be innovative therapeutic agents for the management of NP.

Central nervous system and analgesic profiles of Lippia genus

Abstract Many people use medicinal plants to relieve disorders related to the central nervous system, such as depression, epilepsy, anxiety and pain, even though the effectiveness of most of them has not yet been proven through scientific studies. Plants of the Lippia genus, Verbenaceae, are widely used in ethnobotany as a food, for seasoning and in antiseptic remedies. They are also marketed and used for the treatment of different types of pain, including stomach ache, abdominal pain and headache, as well as being used as sedatives, anxiolytics and anticonvulsants. Despite their widespread use, there are no reviews on the central nervous system profile of plants of this genus. Therefore, the databases Medline-PubMed, Embase, Scopus and Web of Science were searched using the terms Lippia and biologic activity. Thirty-five papers were found. Eleven species of Lippia showed central nervous system activity, with leaves and the aerial parts of plants being the most commonly used, especially in aqueous and ethanol extracts or volatile oil. The species are composed mainly of terpenoids and phenylpropanoids, including polyketides, flavonoids and in less quantity some alkaloids. Although several species of Lippia present analgesic activity, most studies have not explored the mechanisms responsible for this effect, however, there is some evidence that volatile oils and constituents of the extracts may be responsible for the relief of some CNS disorders, but the effects on pain modulation seem to be the most exploited so far.

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.

Chemical composition and antibacterial activity of essential oil from leaves of Croton heliotropiifolius in different seasons of the year

ABSTRACT This paper reports the first study of the variation of the chemical composition and abundance of the essential oil of Croton heliotropiifolius, in four seasons, and the evaluation of its antibacterial activity. Essential oil obtained from leaves of C. heliotropiifolius were analyzed by GC/MS and evaluated against eight bacteria strains by broth microdilution method. The chemical constituents identified were the same in all samples, but with different proportions. The total percentages identified were 96.58% in summer, 92.08% in autumn, 98.44% in winter and 90.78% in spring. The majors constituents are β-caryophyllene, bicyclogermacrene, germacrene-D, limonene and 1,8-cineole. β-Caryophyllene was the major compound in all samples. The results of the antibacterial evaluations showed weak to moderate activity against the analyzed strains. In all analyzes was observed that essential oil sample collected in summer stands out from the others, displaying stronger activity against Gram-positive as Gram-negative bacteria.

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%).

Inclusion of terpenes in cyclodextrins: Preparation, characterization and pharmacological approaches.

Terpenes constitute the largest class of natural products and are important resources for the pharmaceutical, food and cosmetics industries. However, due to their low water solubility and poor bioavailability there has been a search for compounds that could improve their physicochemical properties. Cyclodextrins (natural and derived) have been proposed for this role and have been complexed with different types of terpenes. This complexation has been demonstrated by using analytical techniques for characterizing complexes such as DSC, NMR, XRD, FTIR, and TGA. The formation of inclusion complexes has been able to improve drug characteristics such as bioavailability, solubility and stability; and to enhance biological activity and efficacy. This review shows strong experimental evidence that cyclodextrins improve the pharmacological properties of terpenes, and therefore need to be recognized as being possible targets for clinical use.