Agave tequilana Counteracts Chronic Hypertension and Associated Vascular Damage.

Systemic arterial hypertension (SAH) is a health problem of great importance worldwide, and endothelial dysfunction underlies SAH development. This condition's main characteristics include vasoconstriction, inflammation, oxidative stress, and procoagulant and proliferative states. This study's objective was to evaluate the antihypertensive, anti-inflammatory, and antioxidant effects of the whole extract and fractions of Agave tequilana in a murine model of SAH. SAH was induced in male ICR or CD-1 (Strain obtained from animals from Charles River Laboratories, Massachusetts) mice by intraperitoneal administration of angiotensin II (AGII) (0.1 µg/kg) for 4 weeks, and then A. tequilana treatments were co-administered with AGII. At the end of the experiment, systolic and diastolic blood pressure were measured and the kidneys were dissected to quantify interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, IL-10, and malondialdehyde (MDA). The whole extract and the fractions of A. tequilana were chemically characterized using gas chromatography-mass spectrometry. The results indicate that the whole extract (At-W) and At-AcOEt fraction treatment are the most efficient in lowering blood pressure, although all the treatments had an immunomodulatory effect on the cytokines evaluated and an antioxidant effect on lipid peroxidation. Finally, the chromatographic profile shows that the integral extract and fractions of A. tequilana contained phytol (M)3,7,11,15-Tetramethyl-2-hexadecen-1-ol; 9,12-octadecadienoic acid; hentriacontane; 9,19-cyclolanost-24-en-3-ol,(3b); t-sitosterol; and stigmasta-3,5-dien-7-one.

Characterization of a murine model of endothelial dysfunction induced by chronic intraperitoneal administration of angiotensin II.

Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1ß, IL17A, IL4, TGFß, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.

Synergism and Subadditivity of Verbascoside-Lignans and -Iridoids Binary Mixtures Isolated from Castilleja tenuiflora Benth. on NF-κB/AP-1 Inhibition Activity.

Pharmacodynamic interactions between plant isolated compounds are important to understand the mode of action of an herbal extract to formulate or create better standardized extracts, phytomedicines, or phytopharmaceuticals. In this work, we propose binary mixtures using a leader compound to found pharmacodynamic interactions in inhibition of the NF-κB/AP-1 pathway using RAW-Blue™ cells. Eight compounds were isolated from Castilleja tenuiflora, four were new furofuran-type lignans for the species magnolin, eudesmin, sesamin, and kobusin. Magnolin (60.97%) was the most effective lignan inhibiting the NF-κB/AP-1 pathway, followed by eudesmin (56.82%), tenuifloroside (52.91%), sesamin (52.63%), and kobusin (45.45%). Verbascoside, a major compound contained in wild C. tenuiflora showed an inhibitory effect on NF-κB/AP-1. This polyphenol was chosen as a leader compound for binary mixtures. Verbacoside-aucubin and verbascoside-kobusin produced synergism, while verbascoside-tenuifloroside had subadditivity in all concentrations. Verbascoside-kobusin is a promising mixture to use on NF-κB/AP-1 related diseases and anti-inflammatory C. tenuiflora-based phytomedicines.

Anti-arthritic and anti- inflammatory effects of extract and fractions of Malva parviflora in a mono- arthritis model induced with kaolin/carrageenan.

Malva parviflora is used as food in the gastronomy of some regions of Mexico and, also, in Mexican traditional medicine for inflammation-related conditions like rheumatoid arthritis. The objective of this work was to evaluate its antiarthritic activity in a mice model. In ICR, female mice were tested the dichloromethane extract (MpD) and fractions MpF4 (extracted with a dichoromethane:methanol system) and MpFphy (a precipitate by acetone:methanol) by using the mono-arthritis with kaolin/carrageenan model. During the treatment, joint inflammation was measured daily, and hyperalgesia was measured using the hot plate test. The treatments diminished both joint inflammation and pain. At the end of the evaluation, the left joint and spleen were extracted for determination of pro- and anti-inflammatory cytokines. The results showed that the MpD, MpF4, and MpFphy treatments modulated the concentration of these proteins. Specifically, MpFphy at 1.0 mg/kg increased IL-4 and IL-10 and decreased IL-17, IL-1ß, and TNF-α. GC-MS analysis showed that MpF4 contained a mixture of a total of nine compounds, three of them newly reported for the species. The studies confirmed the presence of five sterols in the MpFphy fraction, including stigmasterol and ß-sitosterol. These results confirm the anti-rheumatoid and anti-inflammatory activities of a fraction rich in sterols from Malva parviflora. Graphical abstract.

A Malva parviflora´s fraction prevents the deleterious effects resulting from neuroinflammation.

Neuroinflammation, a centralized immune response, is a physiological process by which the organism attempts to remove an injurious stimulus in the central nervous system. Nonetheless, it is known that chronic inflammatory processes play an important role in the onset and progression of neurodegenerative disorders, such as Alzheimer´s disease (AD). Based on this, new strategies to treat AD have been proposed. Among them, the use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of this disease. Unfortunately, the prolonged use of NSAIDs results in adverse secondary effects. In this context, plants secondary metabolites have become of great interest. Particularly, our group has demonstrated that the hydroalcoholic extract of Malva parviflora (MpHA) has anti-inflammatory effect and is capable of improving the cognitive deficit present in an AD model. To further characterize the Malva parviflora compounds with anti-inflammatory properties, here we generated a fraction from a dichloromethane extract, which constitutes a less complex mix of compounds than the MpHA. This approach allowed us to isolate a fraction (MpF10) with anti-inflammatory activity, able to ameliorate the spatial learning and memory impairment, and to reduce both astrogliosis as well as IL-1ß and TNF production in a murine model of LPS-mediated neuroinflammation. Among the identified compounds in the MpF10, we found daucosterol (MpDau), which prevented LPS-induced neuroinflammation. Interestingly, MpF10 and MpDau inhibit NFκB activity in macrophages exposed to LPS. Therefore, we propose that the compounds present in the MpF10 represent an alternative to treat neuroinflammation, an important process developed during neurodegenerative diseases such as AD.

Effect of Ocimum basilicum, Ocimum selloi, and Rosmarinic Acid on Cerebral Vascular Damage in a Chronic Hypertension Model.

The main objective of treatment against hypertension is not only to reduce blood pressure levels, but also to reduce vascular risk in general. In the present work, administering angiotensin II (AGII; 0.2 µg/kg intraperitoneally (i.p.) for 12 weeks) activates the hypothalamic-pituitary-adrenal (HPA) axis, which caused an increase in corticosterone levels, as well as in proinflammatory cytokines (interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α)) and macrophage chemotactic protein 1 (MCP-1), and decreased anti-inflammatory cytokines (interleukin 10 (IL-10) and interleukin 4 (IL-4)). On observing the behavior in the different models, an anxiogenic effect (elevated plus maze (EPM)) and cognitive impairment (water Morris maze (WMM)) was observed in animals with AGII. By administering organic extracts from Ocimum basilicum (Oba-EtOAc) and Ocimum selloi (Ose-EtOAc), and some doses of rosmarinic acid (RA) (6 weeks per os (p.o.)), the damage caused by AGII was stopped by re-establishing corticosterone serum levels and by decreasing the proinflammatory cytokines and MCP-1.

Acute and Chronic Antihypertensive Effect of Fractions, Tiliroside and Scopoletin from Malva parviflora.

Hypertension is a disease of high prevalence and morbidity where vascular inflammation and associated oxidative stress (endothelial dysfunction) is the underlying cause of this pathology. We are reporting the antihypertensive activity of extracts and fractions of Malva parviflora in mice with chronic and acute hypertension. Also, the treatments of this plant were able to counteract the kidney inflammation and associated oxidative stress. The chronic hypertension model consisted of administration of angiotensin II (AGII) during 12 weeks, causing a sustained increase in systolic (SBP) or diastolic (DBP) pressure, with values of pharmacological constants of: ED50 = 0.038 mg/kg y Emax = 135 mmHg for SBP and ED50 = 0.046 mg/kg y Emax = 98 mmHg for DBP. The chronic hypertension caused the inflammation and lipid peroxidation in kidneys, measured by of tissue level of cytokines such as interleukin-1ß (IL-1ß), IL-6, Tumor Necrosis Factor-α (TNF-α), IL-10 and malondialdehyde, and treatments for M. parviflora were able to modulate these parameters. The chemical fractionation allowed to identify three compounds: oleanolic acid, tiliroside and scopoletin, which were tested in a model of acute hypertension. The pharmacodynamic parameters for SBP were ED50 = 0.01 and 0.12 mg/kg while Emax = 33.22 and 37.74 mmHg for scopoletin and tiliroside, respectively; whereas that for DBP data were ED50 = 0.01 and 0.02 mg/kg; with an Emax = 7.00 and 6.24 mmHg, in the same order. M. parviflora, is able to counteract the effect of chronic and acute administration of AGII, on hypertension, but also the inflammatory and oxidative damage in the kidney. The oleanolic acid, scopoletin and tiliroside are the compounds responsible for such activities.

Frameless robot-assisted stereoelectroencephalography for refractory epilepsy in pediatric patients: accuracy, usefulness, and technical issues.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective technique to help to locate and to delimit the epileptogenic area and/or to define relationships with functional cortical areas. We intend to describe the surgical technique and verify the accuracy, safety, and effectiveness of robot-assisted SEEG in a newly created SEEG program in a pediatric center. We focus on the technical difficulties encountered at the early stages of this program. METHODS: We prospectively collected SEEG indication, intraoperative events, accuracy calculated by fusion of postoperative CT with preoperative planning, complications, and usefulness of SEEG in terms of answering preimplantation hypothesis. RESULTS: Fourteen patients between the ages of 5 and 18 years old (mean 10 years) with drug-resistant epilepsy were operated on between April 2016 and April 2018. One hundred sixty-four electrodes were implanted in total. The median entry point localization error (EPLE) was 1.57 mm (1-2.25 mm) and the median target point localization error (TPLE) was 1.77 mm (1.2-2.6 mm). We recorded seven intraoperative technical issues. Two patients suffered complications: meningitis without demonstrated germ in one patient and a right frontal hematoma in the other. In all cases, the SEEG was useful for the therapeutic decision-making. CONCLUSION: SEEG has been useful for decision-making in all our pediatric patients. The robotic arm is an accurate tool for the insertion of the deep electrodes. Nevertheless, it is an invasive technique not risk-free and many problems can appear at the beginning of a robotic arm-assisted SEEG program that must be taken into account beforehand.

Frameless robot-assisted pallidal deep brain stimulation surgery in pediatric patients with movement disorders: precision and short-term clinical results.

OBJECTIVE: The purpose of this study was to verify the safety and accuracy of the Neuromate stereotactic robot for use in deep brain stimulation (DBS) electrode implantation for the treatment of hyperkinetic movement disorders in childhood and describe the authors' initial clinical results. METHODS: A prospective evaluation of pediatric patients with dystonia and other hyperkinetic movement disorders was carried out during the 1st year after the start-up of a pediatric DBS unit in Barcelona. Electrodes were implanted bilaterally in the globus pallidus internus (GPi) using the Neuromate robot without the stereotactic frame. The authors calculated the distances between the electrodes and their respective planned trajectories, merging the postoperative CT with the preoperative plan using VoXim software. Clinical outcome was monitored using validated scales for dystonia and myoclonus preoperatively and at 1 month and 6 months postoperatively and by means of a quality-of-life questionnaire for children, administered before surgery and at 6 months' follow-up. We also recorded complications derived from the implantation technique, "hardware," and stimulation. RESULTS: Six patients aged 7 to 16 years and diagnosed with isolated dystonia ( DYT1 negative) (3 patients), choreo-dystonia related to PDE2A mutation (1 patient), or myoclonus-dystonia syndrome SGCE mutations (2 patients) were evaluated during a period of 6 to 19 months. The average accuracy in the placement of the electrodes was 1.24 mm at the target point. At the 6-month follow-up, patients showed an improvement in the motor (65%) and functional (48%) components of the Burke-Fahn-Marsden Dystonia Rating Scale. Patients with myoclonus and SGCE mutations also showed an improvement in action myoclonus (95%-100%) and in functional tests (50%-75%) according to the Unified Motor-Rating Scale. The Neuro-QOL score revealed inconsistent results, with improvement in motor function and social relationships but worsening in anxiety, cognitive function, and pain. The only surgical complication was medial displacement of the first electrode, which limited intensity of stimulation in the lower contacts, in one case. CONCLUSIONS: The Neuromate stereotactic robot is an accurate and safe tool for the placement of GPi electrodes in children with hyperkinetic movement disorders.

Cucumis sativus Aqueous Fraction Inhibits Angiotensin II-Induced Inflammation and Oxidative Stress In Vitro.

Inflammation and oxidative stress play major roles in endothelial dysfunction, and are key factors in the progression of cardiovascular diseases. The aim of this study was to evaluate in vitro the effect of three subfractions (SFs) from the Cucumis sativus aqueous fraction to reduce inflammatory factors and oxidative stress induced by angiotensin II (Ang II) in human microvascular endothelial cells-1 (HMEC-1) cells. The cells were cultured with different concentrations of Ang II and 0.08 or 10 µg/mL of SF1, SF2, or SF3, or 10 µmol of losartan as a control. IL-6 (Interleukin 6) concentration was quantified. To identify the most effective SF combinations, HMEC-1 cells were cultured as described above in the presence of four combinations of SF1 and SF3. Then, the effects of the most effective combination on the expression of adhesion molecules, the production of reactive oxygen species (ROS), and the bioavailability of nitric oxide (NO) were evaluated. Finally, a mass spectrometry analysis was performed. Both SF1 and SF3 subfractions decreased the induction of IL-6 by Ang II, and C4 (SF1 and SF3, 10 µg/mL each) was the most effective combination to inhibit the production of IL-6. Additionally, C4 prevented the expression of adhesion molecules, reduced the production of ROS, and increased the bioavailability of NO. Glycine, arginine, asparagine, lysine, and aspartic acid were the main components of both subfractions. These results demonstrate that C4 has anti-inflammatory and antioxidant effects.

Management in chordoid glioma: Avoiding the pitfalls in this rare and challenging entity.

Chordoid glioma (CG) of the third ventricle is an unusual neoplasm of glial nature, which is almost exclusively located in the anterior wall of the third ventricle, in close relation with the hypothalamus. Magnetic resonance images show CG as a suprasellar, hypo- to isointense mass, homogeneously enhancing after the administration of gadolinium. Since its description in 1998 by Brat et al., approximately 85 cases have been reported. Some of its pathological features are under discussion and its histological origin still remains unclear. In this study, we present a patient having this rare entity. We review the management of CG reported in literature. We also studied its pathological features, the postoperative mortality and morbidity related to radical surgical resection, and the implemented adjuvant therapies. Due to its classical clinical features and its close resemblance to other lesions in the region, it is an entity unlikely to be suspected prior to its histological diagnosis. Despite the benign nature of this tumor, the clinical outcome might be poor. Its treatment may represent a real challenge because it involves critical anatomical areas, leading to high postoperative morbidity and mortality rates. An initial minimally invasive management and adjuvant therapies, such as radiosurgery, in case of symptomatic recurrences, can be effective handling strategies.

Anti-Inflammatory Activity of a Polymeric Proanthocyanidin from Serjania schiedeana.

The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67-89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin-(4ß â†’ 8)-epicatechin-(4ß â†’ 8, 2ß â†’ O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1ß, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen.

Safety and Efficacy of TachoSil (Absorbable Fibrin Sealant Patch) Compared With Current Practice for the Prevention of Cerebrospinal Fluid Leaks in Patients Undergoing Skull Base Surgery: A Randomized Controlled Trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures. OBJECTIVE: To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure. METHODS: Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing ± duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment). RESULTS: A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events. CONCLUSION: Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.

Effect of Hautriwaic Acid Isolated from Dodonaea viscosa in a Model of Kaolin/Carrageenan-Induced Monoarthritis.

In the present work, the antiarthritic activity of hautriwaic acid is reported. This ent-clerodane diterpene isolated from Dodonaea viscosa was evaluated in mice using a kaolin/carrageenan-induced monoarthritis model. The inflammation observed in the joint (knee) on days 1-8 ranged from 50-70 %. After 10 days of treatment with different doses of hautriwaic acid (5, 10, 20 mg/kg), a decrease in knee inflammation was detected. This recovery was observed with both reference drugs, methotrexate (1 mg/kg) and diclofenac (0.75 mg/kg). In these groups of mice, the concentration of proinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the joint was significantly lower than that of the negative control group (animals with damage without any treatment). The negative control group presented a decrease in the concentration of interleukin-10, while the groups that received hautriwaic acid at different dose exhibited an increase in this interleukin. This anti-inflammatory cytokine was not modified in the joint of mice with diclofenac, but in mice that received methotrexate, a significant decrease was observed. Hautriwaic acid isolated from D. viscosa diminished the joint edema induced by this mixture of polysaccharides (carrageenan), possibly by acting as immunomodulator of the inflammatory response.

The extended endoscopic endonasal transplanum transtuberculum approach to the anterior communicating artery complex: anatomic study.

BACKGROUND: When performing a transplanum transtuberculum approach, dealing with the anterior communicating artery (ACoA) complex is inevitable. The aim of this study is to provide quantitative anatomical information regarding the ACoA complex and its bony and neural relationships, when exposed through this approach. METHOD: The endoscopic endonasal transplanum transtuberculum approach was performed on ten human cadaver heads. In each specimen, radiological studies were performed. A three-dimensional model of the approach was reconstructed. Measured parameters were: exposure of the vessels; distance between the proximal anterior cerebral artery (A1) and the optic chiasm; dimension of the bone opening. The feasibility to perform clip placement was graded as "possible" or "not possible". RESULTS: Dimension of bone opening varied from 88 to 53 mm(2). The ACoA was exposed for 3 mm ± 2 mm, A1 for 17 mm ± 9 mm, the distal anterior cerebral artery (A2) for 12 mm ± 3 mm, the recurrent artery of Heubner (RAH) for 16 mm ± 4 mm. Clip placement was possible on the ACoA, A2, and distal segment of A1 in all cases, and on the proximal segment of A1 in one instance. The distance between A1 and the optic chiasm measured 9 mm ± 2 mm. CONCLUSIONS: The ACoA, A2, and the distal segment of A1 can be visualized and controlled through the transplanum transtuberculum approach. The relationship between A1, gyrus rectus, and optic chiasm is the main determinant for the exposure and control of the vessel. The olfactory nerve can represent a surgical landmark for the identification of the A1 origin. The whole course of the RAH can be visualized trough this approach.

Anti-inflammatory, antioxidant and anti-acetylcholinesterase activities of Bouvardia ternifolia: potential implications in Alzheimer's disease.

Bouvardia ternifolia has been used medicinally to treat inflammation. In the present study, we investigate the anti-Alzheimer's potential effect of the hydroalcoholic extract of B. ternifolia through evaluation of anti-inflammatory and antioxidant activities, quantification of the percentage inhibition of acetylcholinesterase activity, protection effect against ß-amyloid fibrillar-induce neurotoxicity, and the identification of the main constituents. Our results show that B. ternifolia extract and ethyl acetate fraction induced anti-inflammatory effects by reducing inflammation by >70 %, while antioxidant test revealed significant IC50 values for flavonoid content fraction (30.67 ± 2.09 µg/ml) and ethyl acetate fraction (42.66 ± 0.93 µg/ml). The maximum inhibition of acetylcholinesterase was exhibited by scopoletin content fraction (38.43 ± 3.94 %), while ethyl acetate fraction exerted neuroprotective effect against ß-amyloid peptide (83.97 ± 5.03 %). Phytochemical analysis, showed the presence of 3-O-quercetin glucopyranoside (415 mg/g), rutin (229.9 mg/g), ursolic and oleanolic acid (54 and 20.8 mg/g respectively), 3-O-quercetin rhamnopyranoside (12.8 mg/g), chlorogenic acid (9.5 mg/g), and scopoletin (1.38 mg/g). Our findings support the use of B. ternifolia since the extract induced significant neuroprotection against ß-amyloid peptide, anti-inflammatory, antioxidant and anti-acetylcholinesterase effects that could be attributed to its contents of polyphenols, coumarins, and triterpenes, and encourage further studies for development of this extract as therapeutic agent in treatment of Alzheimer's disease.

A three-dimensional computer-based perspective of the skull base.

OBJECTIVE: To describe our designed protocol for the reconstruction of three-dimensional (3D) models applied to various endoscopic endonasal approaches that allows performing a 3D virtual dissection of the desired approach and analyzing and quantifying critical surgical landmarks. METHODS: All human cadaveric heads were dissected at the Laboratory of Surgical Neuroanatomy of the University of Barcelona. The dissection anatomic protocol was designed as follows: 1) virtual surgery simulation systems, 2) navigated cadaver dissection, and 3) postdissection analysis and quantification of data. RESULTS: The virtual dissection of the selected approach, the preliminary exploration of each specimen, the real dissection laboratory experience, and the analysis of data retrieved during the dissection step provide a complete method to improve general knowledge of the main endoscopic endonasal approaches to the skull base, at the same time allowing the development of new surgical techniques. CONCLUSIONS: The methodology for surgical training in the anatomic laboratory described in this article has proven to be very effective, producing a depiction of anatomic landmarks as well as 3D visual feedback that improves the study, design, and execution in various neurosurgical approaches. The Dextroscope as a virtual surgery simulation system can be used as a preoperative planning tool that can allow the neurosurgeon to perceive, practice reasoning, and manipulate 3D representations using the transsphenoidal perspective acquiring specifically visual information for endoscopic endonasal approaches to the skull base. The Dextroscope also can be used as an advanced tool for analytic purposes to perform different types of measurements between surgical landmarks before, during, and after dissection.

Endoscopic endonasal surgery for pituitary tumors. Results in a series of 121 patients operated at the same center and by the same neurosurgeon.

INTRODUCTION: Pituitary adenomas account for approximately 15% of intracranial benign tumors. The neurosurgical results achieved since the endoscopic endonasal transsphenoidal (EET) approach was introduced in our center in 2005 are reported here. PATIENTS AND METHODS: A retrospective analysis of 121 patients with sellar lesions (58% females, age 55.7 ± 16 years, range 18-82) who underwent EET surgery from February 2005 to January 2012 and were followed up for a mean time of 4.58 years (range 1.08-8.58). RESULTS: Six Rathke cleft cysts (3 intra-suprasellar, 1 intrasellar, 2 suprasellar); 114 pituitary adenomas (16 microadenomas, 98 macroadenomas), and 1 case of normal MRI were included. Baseline findings included hormonal changes in 59 patients (48,7%) and visual field changes in 38 patients (31%); in 7 patients (5.8%), clinical presentation was pituitary apoplexy. Complete resection was achieved in 77 patients (63.6%), subtotal resection in 29 (23.9%), and partial resection in 15 (12.3%). In patients with Grade 3 and 4 cavernous sinus invasion, resection was subtotal in 30% (12/39) and complete in 46% (18/39). Hormonal remission was achieved in 16 patients with Cushing disease (84%), 18 patients with prolactinoma (78.2%), and 18 patients with acromegaly (85,7%). There were 12 cases (9%) of cerebrospinal fluid leak, 4 cases of diabetes insipidus, and 3 cases with transient SIADH/hyponatremia. Seven patients developed panhypopituitarism. Postoperative mortality rate was 2.4%. One hundred and three patients (85.3%) were discharged from the hospital less than 48 hours after surgery. CONCLUSION: Our results are similar to those reported by renowned pituitary units. Results achieved using an endoscopic approach in pituitary neurosurgery are better than those of microneurosurgery for cavernous sinus invasion.

In vivo anti-inflammatory and anti-ulcerogenic activities of extracts from wild growing and in vitro plants of Castilleja tenuiflora Benth. (Orobanchaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Castilleja tenuiflora Benth. (Orobanchaceae) is a perennial shrub used since the 16(th) century in Mexican traditional medicine for the treatment of a number of health disorders including inflammation, stomach pain and tumors. The aim of the present study was to evaluate the cytotoxic, anti-inflammatory and anti-ulcerogenic activities of ethyl acetate (EaE), methanol (ME) and aqueous extracts (AE) of Castilleja tenuiflora wild grown (CtW) and in vitro plants (CtIv). MATERIAL AND METHOD: Phytochemical analysis of the phenylethanoid glycoside (PhG) and iridoid glycoside (IG) components was carried out by chromatographic methods. In vitro cytotoxic activity of the extracts was evaluated in the following four carcinoma cell lines: colon (HF-6), breast (MCF-7), prostate (PC-3), and nasopharyngeal (KB). The topical anti-inflammatory activity was evaluated in mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Anti-ulcerogenic activity was evaluated in rats using an absolute ethanol-induced acute gastric ulcer model. RESULTS: The main compounds in the extracts were isoverbascoside, verbascoside and aucubin and their concentration depended both on the solvent used and on the plant material origin. None of the extracts showed cytotoxicity against the tested cell lines. In contrast, CtWEaE, CtWAE and CtIvEaE (1.6 mg/ear) showed moderate anti-inflammatory activity similar to dexamethasone (1 mg/ear) with a 38.2, 39.3 and 49.1% decrease of inflammation, respectively. CtWEaE and CtIvEaE (100 mg/kg) showed high anti-ulcerogenic activity with 88.3 and 83.1% inhibition, respectively, compared to famotidine (20 mg/kg, 32.8% inhibition). CONCLUSION: Castilleja tenuiflora extracts provided significant gastric protection in an acute ulcer induction model and topical anti-inflammatory activity in a mouse ear edema model. These activities are related to verbascoside and may explain the traditional use of Castilleja tenuiflora in the treatment of anti-inflammatory and gastrointestinal disorders. Cultured Castilleja tenuiflora plants (in vitro) exhibited pharmacological activities and also have the potential to produce bioactive compounds.

Toxicology, genotoxicity, and cytotoxicity of three extracts of Solanum chrysotrichum.

ETHNOPHARMACOLOGICAL RELEVANCE: Infusions of Solanum chrysotrichum (Schldl.) or "sosa" are employed in Traditional Mexican Medicine for the local and systemic treatment of skin and mucosal infections. Different studies have verified its antifungal effectiveness and therapeutic safety in superficial mycosis caused by dermatophytes or yeasts, and have identified a group of spirostanic saponins, denominated SC-2-SC-6, as responsible for the antifungal activity. Of these, SC-2 is the most active molecule. Electron microscopy studies showed that SC-2 disintegrates cell wall and internal membranes of the fungi studied. In order to continue the systematic study of Solanum chrysotrichum, the goal of the present study was to evaluate the toxicity, genotoxicity, and cytotoxicity of the three different extracts of Solanum chrysotrichum. MATERIALS AND METHODS: From the dried leaves of Solanum chrysotrichum, we obtained the aqueous, hydroalcoholic, and ethanolic extracts. Saponins (SC-2-SC-6) were quantified by High-performance liquid chromatography (HPLC). For the toxicology study, we formed four groups: three experimental groups, treated with each of the extracts at 1-g/kg doses per os (po) during 4 weeks, and a negative control group treated with the vehicle. For the genotoxicity study, we added another group, which was treated with cyclophosphamide for 1 week. The cytotoxicity study was carried out with international methods and employing the nasopharyngeal cancer (KB) and breast cancer (MDA) cell lines. RESULTS: The three evaluated extracts did not modify either of the behavioral parameters, and on the hepatic-function biochemical tests (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), did not showed significant increase on comparing to placebo. The genotoxicity parameters did not exhibit differences between the experimental groups and the placebo (control) group. Histologic analysis showed that the three extracts caused amyloidosis and moderate necrosis in liver, and focal tumefaction in kidney, as well as significant, but clinically irrelevant, elevations of creatinine with the aqueous and hydroalcoholic, but not with the ethanolic, extracts. In addition, the aqueous and ethanolic extracts exhibited interesting cytotoxic activity against the KB cell line. CONCLUSIONS: At the doses administered, the ethanolic extract of Solanum chrysotrichum showed a slightly toxic effect on liver and kidney, without biochemical or genotoxic repercussions and with cytotoxic activity against the KB cell line.