Histomorphometry of mast cells in the convexity of human intracranial dura mater.

Mast cells, known as pro-inflammatory effector cells, are immunocytes present in the meninges and may be involved in the pathophysiology of migraine. This study aims to evaluate the histomorphometric parameters of mast cells located in the convexity of the human intracranial dura mater. For this, samples of intracranial dura mater from eight human fresh cadavers were collected between 8- and 24-h post-mortem. The whole samples were fixed and, subsequently, two fragments of 1.5 cm² each were cut from four different areas of the dura mater convexity, containing a segment of the middle meningeal artery, totaling 64 fragments. After histological processing, the fragments were submitted to microtomy (5 and 10 µm), stained with toluidine blue (0.1%), or immunohistochemically labeled for tryptase, and analyzed using optical microscopy. The following histomorphometric parameters were evaluated: distance from mast cells to vessels, the density of mast cells, and percentage of mast cells with degranulation. Histomorphometric analyzes showed a higher density of mast cells in the vicinity of blood vessels (arterial and venous), with distances around 0-150 µm. A greater number of mast cells was detected near venous vessels in the periosteal layer (17.0 ± 10.1 cells/mm²) than in the meningeal layer (14.1 ± 7.0 cells/mm²) (p < 0.05). Mast cells from the region close to the superior sagittal sinus were found in greater quantity close to the venous vessels (16.7 ± 10.1 cells/mm²) than to the arterial vessels (11.2 ± 7.5 cells/mm²) (p < 0.05). In short, in the convexity of the human intracranial dura mater, mast cells are located close to blood vessels, with a greater number of cells next to the venous vessels of the periosteal layer and in the proximal region of the superior sagittal sinus.

Anticonvulsant, Anxiolytic and Antidepressant Properties of the ß-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems.

BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.

Indigofera suffruticosa Mill. (Anil): Plant Profile, Phytochemistry, and Pharmacology Review.

Indigoferasuffruticosa Mill. (Fabaceae) is known as anil or anileira and also with other names, due to the production of a blue pigment, which is commonly used for yarn dyeing. It is distributed in some states of Brazil (Pernambuco, Paraíba, Mato Grosso, São Paulo, Bahia, Pará, and others) and is used in the popular medicine as a febrifuge, antispasmodic, diuretic, abortive, analgesic, purgative, or soothing agent against stomach and urinary problems, jaundice, and ulcers and also as an insecticide. In addition, I. suffruticosa can be used as animal feed. This review aimed at providing important data on the botanical, distribution, ethnopharmacology, phytochemical, pharmacological, and toxicity of I. suffruticosa based on the scientific literature. Information on I. suffruticosa was gathered via the Internet (from Elsevier, NCBI, and Sci-Hub) and libraries in the period from February to March 2016. More than 40 chemical compounds have been identified and a few compounds isolated, and the main origins are the essential oils, organic extracts, and aqueous extracts of different parts of the plant. I. suffruticosa and its active compounds possess wide pharmacological actions in the literature, such as anti-inflammatory, antibacterial, antifungal, antioxidative, antitumor, antimutagenic, anticonvulsant, gastroprotective, and hepatoprotective activities. Therefore, as an important traditional popular medicine, further studies on I. suffruticosa are required for the development of new drugs and therapeutics for various diseases.

Nerolidol-loaded nanospheres prevent behavioral impairment via ameliorating Na+, K+-ATPase and AChE activities as well as reducing oxidative stress in the brain of Trypanosoma evansi-infected mice.

The aim of this study was to investigate the effect of nerolidol-loaded nanospheres (N-NS) on the treatment of memory impairment caused by Trypanosoma evansi in mice, as well as oxidative stress, and Na+, K+-ATPase and acetylcholinesterase (AChE) activities in brain tissue. Animals were submitted to behavioral tasks (inhibitory avoidance task and open-field test) 4 days postinfection (PI). Reactive oxygen species (ROS) and thiobarbituric acid-reactive substance (TBARS) levels and catalase (CAT), superoxide dismutase (SOD), Na+, K+-ATPase and AChE activities were measured on the fifth-day PI. T. evansi-infected mice showed memory deficit, increased ROS and TBARS levels and SOD and AChE activities, and decreased CAT and Na+, K+-ATPase activities compared to uninfected mice. N-NS prevented memory impairment and oxidative stress parameters (except SOD activity), while free nerolidol (N-F) restored only CAT activity. Also, N-NS treatment was able to prevent alterations in Na+, K+-ATPase and AChE activities caused by T. evansi infection. A significantly negative correlation was observed between memory and ROS production (p < 0.001; r = -0.941), as well as between memory and AChE activity (p < 0.05; r = -0.774). On the contrary, a significantly positive correlation between memory and Na+, K+-ATPase activity was observed (p < 0.01; r = 0.844). In conclusion, N-NS was able to reverse memory impairment and to prevent increased ROS and TBARS levels due to amelioration of Na+, K+-ATPase and AChE activities and to activation of the antioxidant enzymes, respectively. These results suggest that N-NS treatment may be a useful strategy to treat memory dysfunction and oxidative stress caused by T. evansi infection.

Antimicrobial Activity and Phytochemical Analysis of Organic Extracts from Cleome spinosa Jaqc.

Due to the use of Cleome spinosa Jacq. (Cleomaceae) in traditional medicine against inflammatory and infectious processes, this study evaluated the in vitro antimicrobial potential and phytochemical composition of extracts from its roots and leaves. From leaves (L) and roots (R) of C. spinosa different extracts were obtained (cyclohexane: ChL and ChR; chloroform: CL and CR; ethyl acetate: EAL and EAR, methanol: ML and MR). The antimicrobial activity was evaluated by the broth microdilution method to obtain the minimum inhibitory (MIC) and microbicidal (MMC) concentrations against 17 species, including bacteria and yeasts. Additionally, antimicrobial and combinatory effects with oxacillin were assessed against eight clinical isolates of Staphylococcus aureus. All C. spinosa extracts showed a broad spectrum of antimicrobial activity, as they have inhibited all tested bacteria and yeasts. This activity seems to be related to the phytochemicals (flavonoid, terpenoids and saponins) detected into the extracts of C. spinosa. ChL and CL extracts were the most actives, with MIC less than 1 mg/mL against S. aureus, Bacillus subtilis, and Micrococcus luteus. It is important to note that these concentrations are much lower than their 50% hemolysis concentration (HC50) values. Strong correlations were found between the average MIC against S. aureus and their phenolic (r = -0.89) and flavonoid content (r = -0.87), reinforcing the possible role of these metabolite classes on the antimicrobial activity of C. spinosa derived extracts. Moreover, CL and CR showed the best inhibitory activity against S. aureus clinical isolates, they also showed synergistic action with oxacillin against all these strains (at least at one combined proportion). These results encourage the identification of active substances which could be used as lead(s) molecules in the development of new antimicrobial drugs.

Successive blood pressure measurements to evaluate suspected and treated hypertension.

INTRODUCTION: According to the published literature, blood pressure (BP) measurements performed in the outpatient clinical setting are often inaccurate. The white coat effect and improper technique are the main causes of this imprecision. Construction of a set of readings without them could improve the accuracy of BP measurement. OBJECTIVE: To evaluate the accuracy and agreement of successive office BP measurements using the awake blood pressure average (ABPa) as the gold standard. METHODS: BP was measured in 852 patients using three techniques: in office (OBPa); seven successive measurements performed by a nurse using an automatic device; and 24 h of ambulatory BP monitoring. BP averages (BPa) were obtained from the nurse's measurements: 1-2BPa (first and second), 3-7BPa (third to seventh), and 1-7BPa (first to seventh). OBPa and successive measurements were tested against ABPa by calculating the following: average difference in BP of 1-2BPa, 3-7BPa and OBPa, and the area under the curve. RESULTS: Among the 834 patients eligible, 374 (43.9%) were considered to be hypertensive on the basis of the ABPa (≥135/85 mmHg). 3-7BPa showed the lowest average difference (4/3 mmHg). By contrast, OBPa showed the highest result (21/11 mmHg). The mean difference with 1-2BPa was 8/4 mmHg. The areas under the curve were better with 3-7BPa (0.82-0.85) and 1-2BPa (0.82-0.83) than OBPa (0.67-0.71) for both systolic and diastolic BP. CONCLUSION: All means from successive measurements showed a better precision than OBPa, even the two first readings. However, more research needs to be carried out before recommendation of the use of this technique in routine practice.