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Although Phoenix dactylifera dates are traditionally consumed for their health benefits, no research has been done on the vascular response in hypertensive animals. This study evaluated the vascular relaxation of hydroalcoholic extracts from seeds of three varieties of P. dactylifera; Sukkari seed (SS), Ajwa seed (AS), and Mabroom seed (MS) on L-NAME-induced hypertension and spontaneously hypertensive rats (SHR). Results showed that all extracts (10 µg/mL) caused relaxations higher than 60% in the aortic rings precontracted with 10 - 6 M phenylephrine in normotensive rats, the SS extract was the most potent. Endothelial nitric oxide (NO) pathway is involved as significantly reduced vascular relaxation in denuded-endothelium rat aorta and with an inhibitor (10 - 4 M L-N ω -Nitro arginine methyl ester; L-NAME) of endothelial nitric oxide synthase (eNOS). Confocal microscopy confirmed that 10 µg/mL SS extract increases NO generation as detected by DAF-FM fluorescence in intact aortic rings. Consistent with these findings, vascular relaxation in intact aortic rings at 10 µg/mL SS extract was significantly decreased in L-NAME-induced hypertensive rats (endothelial dysfunction model), but not in SHR. In both hypertensive models, the denuded endothelium blunted the vascular relaxation. In conclusion, the hydroalcoholic extract of the seed of P. dactylifera (Sukkari, Ajwa and Mabroom varieties) presents a potent endothelium-dependent vascular relaxation, via NO, in normotensive rats as well as in two different models of hypertension. This effect could be mediated by the presence of phenolic compounds identified by UHPLC-ESI-MS/MS, such as protocatechuic acid, and caftaric acid., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes in humans a chronic metabolic disorder characterised by hyperglycaemia, it is associated with an increased risk of cardiovascular disease, disruptions to metabolism and vascular functions. It is also linked to oxidative stress and its complications. Its role in vascular dysfunctions is generally reported without detailed impact on the molecular mechanisms. Potassium ion channel (K + channels) are key regulators of vascular tone, and as membrane proteins, are modifiable by oxidant stress associated with diabetes. This review manuscript examined the impact of oxidant stress on vascular K + channel functions in diabetes, its implication in vascular complications and metabolic and cardiovascular diseases.

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca 2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca 2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1 ) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca 2+ uniporter (MCU) enhance Ca 2+ -dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2 ) Female VSMCs have lower cytosolic Ca 2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α 1C (Ca V 1.2), Na + -K + -2Cl - symporter (NKCC1), and the Na + /K + -ATPase. 3 ) When compared with androgens, the influence of estrogens on Ca 2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4 ) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5 ) Sex-dependent differences in Ca 2+ signaling mean both sexes ought to be included in experimental design.

Senecio nutans Sch. Bip is an endemic plant commonly employed in the Andes culture to counteract the effects of mountain sickness, and its bioactive molecules could provide new drugs for treating hypertension. The purpose was to determine whether the vascular response of the plant bioactive molecules, such as (5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane; Sn-I), could be improved by a simple structural modification to synthesize oximes (Ox-Sn-I). We characterized both compounds using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). We investigated vascular relaxation mechanisms in response to Sn-I and Ox-Sn-I using rat aorta and vascular smooth muscle cells (A7r5) as experimental models. Preincubation of aortic rings with Sn-I (10 -5 M) significantly ( p < 0.001) decreased the contractile effect in response to phenylephrine (PE) and potassium chloride (KCl). The sensitivity (EC 50 ) to PE significantly ( p < 0.01) decreased in the presence of Sn-I (10 -5 M), but not with Ox-Sn-I. Sn-I significantly ( p < 0.001) reduced the PE-induced contraction under calcium-free conditions. When A7r5 cells were preincubated with Sn-I and Ox-Sn-I (10 -5 M), both compounds blunted the increase in intracellular Ca 2+ induced by KCl. 2,3-Dihydrobenzofurane derived from S. nutans (Sn-I) reduces the contractile response probably by blocking Ca 2+ entry through voltage-gated Ca 2+ channels (VGCC) in vascular smooth cells. This effect also causes relaxation in rat aorta mediated by reduction of intracellular Ca 2+ concentration, rather than an increase of NO generation in endothelial vascular cells., Competing Interests: No conflicts of interest, financial or otherwise, are declared by the authors., (This journal is © The Royal Society of Chemistry.)

Introduction: Hypoglycemia and anemia are associated with diabetes mellitus. Medicinal plants and orthodox drugs have been used for the management of this disease. This study aimed to validate the ethnomedical claims of Terminalia catappa Linn. leaf extract in reducing hyperglycemia and hematological potentials in alloxan-induced diabetic rats and to identify likely antidiabetic compounds., Materials and Methods: Ultra-high-performance liquid chromatography was used to identify the various phytochemical constituents. Male Wistar rats were randomly divided into five groups containing 6 rats per group. Group 1 (control) received 0.2 ml/kg of distilled water, group 2 received 130 mg/kg of T. catappa aqueous extract, groups 3-5 were diabetic and received 0.2 ml/g distilled water, 130 mg/kg T. catappa extract and 0.75 IU/kg insulin respectively for 14 days. Hematological parameters were measured and an oral glucose tolerance test was carried out using 2 g/kg body weight glucose. A histological analysis of the pancreas was done., Results: Twenty-five compounds identified as flavonoids, phenolic acids, tannins, and triterpenoids were detected. The blood glucose levels were significantly (p <0.05) elevated in DM groups but were significantly (p <0.05) reduced following Terminalia catappa leaves extract to DM groups. There was s significant (p <0.05) increase in insulin levels improved hematological parameters (RBC, WBC, and platelets), and increased islet population., Conclusion: These results suggest that T. catappa extract has hypoglycemic, insulinogenic, and hematopoietic potentials in diabetic condition and offer protection to the pancreas which could be attributed to the phytochemical constituents thereby justifying its use in traditional therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This paper presents a new variant of the distally based lateral arm fasciocutaneous flap that involves a straightforward and easy dissection as no specific vessel identification or inclusion is needed. Ten fresh cadavers were dissected to study the vascular supply. All three recurrent arteries-radial, ulnar, and interosseus-nourish the flap. The study also identified muscular perforators from the radial recurrent artery, piercing brachioradialis, and, in addition, septocutaneous perforators from the ulnar and interosseous recurrent arteries entering the base of the flap. Clinical application in 12 patients with upper limb burns including antecubital fossa contracture is also reported. This is a reliable and reproducible flap. The clinical dissection is straightforward and easy, with no need to identify or include a specific vessel at the base of the flap. Harvest requires neither the microscope nor loupes and can be done without a tourniquet, so it can be used in even the most modest surgical settings., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: In the past few years, the Canary Islands received immigrants from sub-Saharan countries that arrive to the coast after long boat trips in extreme adverse conditions. The named «trench foot» is a previously described infectious entity developed after feet wounds that get infected by being in contact with water, urine and excrements in these small and crowded boats. We describe a new clinical entity, not published yet, that consists in massive edema in the extremities associating necrosis of the skin and subcutaneous tissue that characteristically respects the muscle and with a non-infectious etiology., Material and Methods: A database including 86 patients arrived by boat («patera») from sub-Saharan countries from September 2020 to January 2022 was made and 39 qualitative and quantitative items were analyzed. The Research Unit performed an observational prospective statistical analysis., Results: A total of 16 patients developed the entity described as necrotizing cellulitis. Its physiopathology completely differs from the one described in the trench foot, since all the cultures resulted sterile., Conclusions: We postulate an inflammatory theory due to the osmotic effect from ingesting sea water and/or the aggressive fluid reposition when they arrive to the emergency room with severe dehydration and hypernatremia. Early surgical evacuation of the edema with escharotomies incisions alleviate the symptoms and prevents progression of the disorder., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Drimys winteri J.R. Forst. & G. Forst (D.C) G. Gray, var. chilensis (canelo) is an endemic tree from Chile. Since pre-Columbian times, it has produced a fruit known as the canelo pepper, (pimienta de canelo) or Foye pepper, which can be used as a spice. The chemical and biological analysis of canelo fruits is reported for the first time in this study, that is, its phenolic fingerprinting by UHPLC-PDA- Q-orbitrap MS, the antioxidant activity, the enzymatic inhibitory activity, and its relaxation effects on rat aorta. The proximal composition and the mineral content (Ca: 1.45 ± 0.03 mg/100 g; Mg: 7.72 ± 0.03 mg/100 g; Fe: 4.54 ± 0.21 mg/100 g; Zn: 2.99 ± 0.02 mg/100 g; Mn: 1.08 ± 0.03 mg/100 g; Cu: 0.82 ± 0.02 mg/100 g; K: 53.03 ± 0.20 mg/100 g; Na: 0.087 ± 0.00 mg/100 g) are also reported. The canelo fruits showed a total phenolic content of 57.33 ± 0.82 mg GAE/g dry weight. In addition, the total flavonoid content was 38.42 ± 1.32 mg equivalent of QE/g dry weight. The antioxidant activity was evaluated by employing DPPH and ABTS methods (IC 50 of 6.65 ± 0.5 and 9.5 ± 0.05 μg/mL, respectively), ORAC (25.33 ± 1.2 μmol Trolox/g dry plant) and FRAP (45.56 ± 1.32 μmol Trolox/g dry plant). The enzymatic inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase (IC 50 : 1.94 ± 0.07, 2.73 ± 0.05, and 9.92 ± 0.05 µg extract/mL, respectively) is also reported. Canelo extract led to an 89% relaxation of rat aorta. Our results confirm that D. winteri fruits are a rich source of secondary metabolites and can inhibit enzymes associated with neurodegenerative diseases; the results also suggest that canelo may induce a potentially hypotensive effect in rat aorta. The study demonstrates the medicinal properties of canelo fruit and spice.

Azara dentata Ruiz & Pav. is a small Chilean native plant from Patagonia, a producer of small white reddish berries. For the first time, the proximal analysis of the fruits, phenolic fingerprinting, the antioxidant activity, and the enzymatic inhibition and relaxation effects in rat aorta induced by the ethanolic extract of these fruits were investigated. The proximal composition and the mineral (Ca: 2434 ± 40 mg/kg; Mg: 702 ± 13 mg/kg; Fe: 117.1 ± 1.6 mg/kg; Zn: 16.1 ± 0.4 mg/kg) and heavy metal (As: 121 ± 11 µg/kg; Cd: 152 ± 5 µg/kg; Hg: 7.7 ± 1.3 µg/kg; Pb 294 ± 4 µg/kg) contents were analyzed. Anthocyanins, flavonoids, phenolic acids, and coumarins were identified using UHPLC-PDA-QTOF-MS. The ethanolic extracts showed a total phenolic content of 23.50 ± 0.93 mg GAE/g extract. In addition, the antioxidant activity was assessed using both DPPH and TEAC (28.64 ± 1.87 and 34.72 ± 2.33 mg Trolox/g of dry fruit, respectively), FRAP (25.32 ± 0.23 mg Trolox equivalent/g dry fruit), and ORAC (64.95 ± 1.23 mg Trolox equivalents/g dry fruit). The inhibition of enzymatic activities (acetylcholinesterase IC 50 : 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC 50 : 6.73 + 0.07 µg extract/mL, amylase IC 50 : 5.6 ± 0.0 µg extract/mL, lipase IC 50 : 30.8 ± 0.0 µg extract/mL, and tyrosinase IC 50 : 9.25 ± 0.15 µg extract/mL) was also assessed. The extract showed 50-60% relaxation in rat aorta (intact), mediated thorough the release of endothelial nitric oxide. Our results suggest that A. dentata is a good source of compounds with the capacity to inhibit important enzymes, can be hypotensive, and can thus have good potentiality as supplements in the amelioration of neurodegenerative diseases and could also have potential to be used to develop new functional foods. The study highlights the benefits of these neglected small fruits and could boost their consumption.

Ethnopharmacology Relevance: The plant Senecio nutans SCh. Bip. is used by Andean communities to treat altitude sickness. Recent evidence suggests it may produce vasodilation and negative cardiac inotropy, though the cellular mechanisms have not been elucidated., Purpose: To determinate the mechanisms action of S. nutans on cardiovascular function in normotensive animals., Methods: The effect of the extract on rat blood pressure was measured with a transducer in the carotid artery and intraventricular pressure by a Langendorff system. The effects on sheep ventricular intracellular calcium handling and contractility were evaluated using photometry. Ultra-high-performance liquid-chromatography with diode array detection coupled with heated electrospray-ionization quadrupole-orbitrap mass spectrometric detection (UHPLC-DAD-ESI-Q-OT-MSn) was used for extract chemical characterization., Results: In normotensive rats, S. nutans (10 mg/kg) reduced mean arterial pressure (MAP) by 40% (p < 0.05), causing a dose-dependent coronary artery dilation and decreased left ventricular pressure. In isolated cells, S. nutans extract (1 μg/ml) rapidly reduced the [Ca 2+ ] i transient amplitude and sarcomere shorting by 40 and 49% (p < 0.001), respectively. The amplitude of the caffeine evoked [Ca 2+ ] i transient was reduced by 24% (p < 0.001), indicating reduced sarcoplasmic reticulum (SR) Ca 2+ content. Sodium-calcium exchanger (NCX) activity increased by 17% (p < 0.05), while sarcoendoplasmic reticulum Ca 2+ -ATPase (SERCA) activity was decreased by 21% (p < 0.05). LC-MS results showed the presence of vitamin C, malic acid, and several antioxidant phenolic acids reported for the first time. Dihydroeuparin and 4-hydroxy-3-(3-methylbut-2-enyl) acetophenone were abundant in the extract., Conclusion: In normotensive animals, S. nutans partially reduces MAP by decreasing heart rate and cardiac contractility. This negative inotropy is accounted for by decreased SERCA activity and increased NCX activity which reduces SR Ca 2+ content. These results highlight the plant's potential as a source of novel cardio-active phytopharmaceuticals or nutraceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gypothamnium pinifolium Phil. (Asteraceae) is a small shrub that grows in the Paposo Valley of the II Antofagasta Region of Chile. This initial study is of the high-resolution phenolic fingerprinting, antioxidant activity, the relaxation effects in rat aorta, the inhibitory enzyme potential, plus the antiproliferative activity of the ethyl acetate and n -hexane extract from G. pinifolium and its two major isolated secondary metabolites (one coumarin: 2- nor -1,2-secolycoserone, and one diterpene: ent -labda-8,13- E -diene-15-ol). The study involves using ultra-high-performance liquid chromatography todiode array detection coupled with Q-Orbitrap mass spectrometry analysis (UHPLC-PDA-Orbi-trap-MS), in which various compounds were identified, including specific coumarins. The n -hexane extract showed total phenolic and flavonoid contents of 517.4 ± 12.5 mg GAE/100 g extract and 72.3 ± 3.7 mg QE/100 g extract, respectively. In addition, the antioxidant activity of the n -hexane extract was assessed using in-vitro assays such as bleaching of DPPH and ABTS (IC 50 : 14.3 ± 0.52 and 2.51 ± 0.43 µg extract/mL, respectively), FRAP (347.12 ± 1.15 μmol Trolox equivalent/g extract), and ORAC (287.3 ± 1.54 μmol Trolox equivalents/g extract). Furthermore, the inhibition against cholinesterases (acetylcholinesterase (AChE) 4.58 ± 0.04 µg/mL, butyrylcholinesterase (BChE) IC 50 : 23.44 ± 0.03 µg/mL) and tyrosinase (IC 50 : 9.25 ± 0.15 µg/mL) enzymes of the n -hexane extract, and main compounds (IC 50 : 1.21 ± 0.03 µg/mL, 11.23 ± 0.02 µg/mL, 3.23 ± 0.12 µg/mL, and 103.43 ± 16.86 µg/mL, correspondingly for the most active coumarin 1) were measured. The antiproliferative potential of the extracts and the two principal compounds against several solid human cancer cells was investigated. All of them showed good activity against cancer cells. Label-free live-cell imaging studies on HeLa cells exposed to the isolated coumarin and the diterpene enabled the observation of cell death and several apoptotic hallmarks. Our results indicate that G. pinifolium Phil. is a valuable source of secondary metabolites with potential activity against noncommunicable diseases.

•The literature reporting on rural-urban health status disparities remains inconclusive.•We analyzed data from a longitudinal population-based study using individual observations.•Our results show that the risks of all-cause and cancer mortality are greater in large cities than in other municipalities, with no clear urban-rural gradient.•Not differences were found among territories in cardiovascular mortality., Competing Interests: None., (© 2022 The Authors.)

Lepidium meyenii Walp (red maca) is a high Andean plant cultivated since the Incas and has innumerable therapeutic properties. The study aims to identify its phytochemical composition using UHPLC-ESI-MS/MS, and evaluate its effects on acrylamide-induced oxidative stress. The lyophilized aqueous extract of red maca (LAqE-RM) was orally administered in doses of 1 and 2 g/kg body weight for 4 weeks. Malondialdehyde (MDA) levels in erythrocytes, brain, and liver, as well as hepatic levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Administration of acrylamide for 2 and 4 weeks significantly increased (p < 0.001) MDA levels in erythrocytes, brain, and liver. However, LAqE-RM prevented (p < 0.001) an increase in MDA levels in all tissues studied. Likewise, the groups treated with LAqE-RM presented significantly (p < 0.001) lower levels of ALT and AST compared to the control. Treatment with LAqE-RM ameliorated the acrylamide-induced oxidative stress by reducing MDA levels in erythrocytes, brain, and liver and by lowering liver levels of ALT and AST in a dose-dependent manner. Twenty-five secondary metabolites were identified and characterized from LAqE-RM based on UHPLC mass spectrophotometry. These include carbolines, alkamides, fatty acids, and macamides, which are probably involved in their antioxidant protective role., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Senecio nutans Sch. Bip. and its constituents are reported to have antihypertensive effects. We isolated metabolite−1, a natural compound from S. nutans (4-hydroxy-3-(isopenten-2-yl)-acetophenone), and synthesized novel oxime − 1 (4-hydroxy-3-(isopenten-2-yl)-acetophenoxime) to evaluate their effect on vascular reactivity. Compounds were purified (metabolite−1) or synthetized (oxime−1) and characterized using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). Using pharmacological agents such as phenylephrine (PE) and KCl (enhancing contraction), acetylcholine (ACh), L-NAME (nitric oxide (NO) and endothelial function), Bay K8644-induced CaV1.2 channel (calcium channel modulator), and isolated aortic rings in an organ bath setup, the possible mechanisms of vascular action were determined. Pre-incubation of aortic rings with 10−5 M oxime−1 significantly (p < 0.001) decreased the contractile response to 30 mM KCl. EC50 to KCl significantly (p < 0.01) increased in the presence of oxime−1 (37.72 ± 2.10 mM) compared to that obtained under control conditions (22.37 ± 1.40 mM). Oxime−1 significantly reduced (p < 0.001) the contractile response to different concentrations of PE (10−7 to 10−5 M) by a mechanism that decreases Cav1.2-mediated Ca2+ influx from the extracellular space and reduces Ca2+ release from intracellular stores. At a submaximal concentration (10−5 M), oxime−1 caused a significant relaxation in rat aorta even without vascular endothelium or after pre-incubate the tissue with L-NAME. Oxime−1 decreases the contractile response to PE by blunting the release of Ca2+ from intracellular stores and blocking of Ca2+ influx by channels. Metabolite−1 reduces the contractile response to KCl, apparently by reducing the plasma membrane depolarization and Ca2+ influx from the extracellular space. These acetophenone derivates from S. nutans (metabolite−1 and oxime−1) cause vasorelaxation through pathways involving an increase of the endothelial NO generation or a higher bioavailability, further highlighting that structural modification of naturally occurring metabolites can enhance their intended pharmacological functions.

Objective: The study was performed to assess if hematological mechanisms such as blood flow modulation, P50 and Oxygen haemoglobin dissociation are involved in Artocarpus altilis leaf extract amelioration of Isoproterenol-Induced Myocardial Damage in rats., Methods: Twenty (20) adult male Sprague-Dawley rats were randomly divided into 5 groups. Group 1 served as the control, group 3 and 5 received 50 and 100 mg/kg Artocarpus altilis water extract, respectively, after being induced with Isoproterenol twice (85 mg/ kg) at a 24-hour period. Group 2 received 85mg/kg isoproterenol only, while group 4 received 50 mg/kg Artocarpus altilis extract only for 6 days. The Hematological parameters were assessed using an automatic Coulter Counter, blood flow was assessed with the CODA machine using the tail cuff method, while blood viscosity was measured at native hematocrit and the oxygen haemoglobin dissociation curves were assessed with the BioProfiler and Hemox Analyzer at the end of seven days., Results: Artocarpus altilis treatment ameliorated the ISO induced increases in viscosity, increased the ISO induced decreased blood flow and influenced oxygen release through its effects on the P50 of the oxygen hemoglobin dissociation curve, AA treatment also reversed the ISO induced weight loss. Apart from the changes in MCH, MCV, there were no significant differences in hematological parameters., Conclusion: This study reported the effects of Artocarpus atilis on the improvement of oxygen availability, the reduction of blood viscosity, and the improvement of blood flow through its influence on endothelial functions and NO availability. Our study further highlights The usefulness of A.atilis, as having a beneficial cardiovascular and haematological outcome in experimental myocardial infarction and as such, potential drug discovery for diseases of cardiovascular & hematological involvement., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Study Objectives: Epidemiologic studies of obstructive sleep apnea (OSA) and insomnia in the U.S. military are limited. The primary aim of this study was to report and compare OSA and insomnia diagnoses in active duty the United States military service members., Method: Data and service branch densities used to derive the expected rates of diagnoses on insomnia and OSA were drawn from the Defense Medical Epidemiology Database. Single sample chi-square goodness of fit tests and independent samples t-tests were conducted to address the aims of the study., Results: Between 2005 and 2019, incidence rates of OSA and insomnia increased from 11 to 333 and 6 to 272 (per 10,000), respectively. Service members in the Air Force, Navy, and Marines were diagnosed with insomnia and OSA below expected rates, while those in the Army had higher than expected rates (p < .001). Female service members were underdiagnosed in both disorders (p < .001). Comparison of diagnoses following the transition from ICD 9 to 10 codes revealed significant differences in the amounts of OSA diagnoses only (p < .05)., Conclusion: Since 2005, incidence rates of OSA and insomnia have markedly increased across all branches of the U.S. military. Despite similar requirements for overall physical and mental health and resilience, service members in the Army had higher rates of insomnia and OSA. This unexpected finding may relate to inherent differences in the branches of the military or the role of the Army in combat operations. Future studies utilizing military-specific data and directed interventions are required to reverse this negative trend., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Fat grafting is a procedure commonly used in breast reconstruction nowadays. Nevertheless, its oncological safety remains controversial. The potential risk that progenitor cells included in fat graft tissue may contribute to disease progression in patients with breast cancer is still debatable. We have designed a matching-cohort study with 250 patients with history of breast cancer trying to elucidate an answer for this question., Methods: We selected 250 patients with a history of breast cancer in our hospital, between 2011 and 2019. A total of 125 patients (cases) had a history of breast cancer reconstructed with fat grafting. The additional 125 patients are matched controls. We analyzed the distribution of eight different variables within the cases and their matched controls: date of first oncological surgery, age, type of oncological surgery, histological subtype, Her-2 status, pN, smoking habit and diabetes mellitus. The objective of this study was to analyze the influence of fat grafting over breast cancer recurrence., Results: There are not statistically significant differences in breast cancer locoregional recurrences (P=0.183), distant metastases (P=0.200) or total recurrences (P=0.065) amongst the two groups (cancer cases and matched controls)., Conclusions: Our study adds more information over the oncological safety of fat grafting. These findings should encourage long-term prospective trials to provide surgeons with accurate information regarding the role of lipofilling on breast neoplasms., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-775). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Abstract: Vasomotion is defined as rhythmic oscillations in arterial diameter that regulate the blood flow and blood pressure. Because antitumor treatment may impair vascular functions and increase the blood pressure, we sought to evaluate whether a new naphthoquinone derivative, postulated as an antitumor agent, manifests adverse effects on vascular function. In this article, we evaluated the toxicity of 2-(4-hydroxyphenyl) amino-1,4-naphthoquinone (Q7) and its effects on vascular vasomotion in 3 models of vascular structure: endothelial cells, aortic ring, and smooth muscle cells. Although showing nontoxic effects, Q7 inhibited the formation of capillary-like structures of the EA.hy926 endothelial cell line grown on Matrigel. In exvivo experiments with aortic rings precontracted with phenylephrine (PE, 10-6 M), Q7 (10-5 M) significantly (P < 0.05) reduced vascular rhythmic contractions induced by the acetylcholine (ACh; 10-7-10-5 M), whereas sodium nitroprusside (a nitric oxide donor; 10-8 M) recovered the vasomotion. Furthermore, Q7 (10-5 M) did not decrease KCl-induced vascular rhythmic contractions in the aortic rings precontracted with BaCl2 (a nonselective K+ channel blocker; 10-3 M). Vascular smooth muscle cells (A7r5) preincubated with Q7 (10-5 M) for 3 hours also demonstrated a reduced glucose uptake. However, the Adenosine Triphosphate content was unaffected, suggesting that the rapid reduction in vasomotion observed in vascular reactivity experiments did not involve cellular metabolism but may be due to faster mechanisms involving endothelial nitric oxide and K+ channels leading to oscillations in intracellular Ca2+. In summary, the naphthoquinone derivative Q7 presents low cytotoxicity yet may alter the endothelial cell response and vasomotion in the absence of changes in smooth muscle cell metabolism., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Hormone Replacement Therapy (HRT) and herbal remedies are often used to alleviate menopausal symptoms, but their effects and efficacy at high altitudes presents with several uncertainties. The purpose of this study was to evaluate whether pre-treatment with maca ( Lepidium meyenii Walp) improved the tolerance to high altitude on an ovariectomized (OVX) rat model at sea level., Method: The animals were treated with 17β-estradiol (200 µg/kg; E2), red and black maca (1.5 g/kg) for 28 days and exposed at high altitude or sea level., Result: Our findings showed that red and black maca extracts significantly ( P  < .001) reduced the MDA level in OVX rat serum under hypoxia in a similar way to E2. Red and black maca extracts had similar effects with E2, by significantly ( P  < .001) reversing and increasing the ovariectomized induced decrease in cornified endometrial cell number. Under hypoxic conditions, the black maca ( P  < .05) and E2 ( P  < .01) increased the uterine weight in OVX rats. Finally, E2 alone significantly recovered the frequency of the uterine contractile response., Conclusion: Aqueous extract of L. meyenii partially protects the reproductive function in hypobaric hypoxic environment, through the recovery of the cornified endometrial cells and uterine weight in a menopausal model of OVX rats., Competing Interests: Roberto O. Ybañez‐Julca, Daniel Asunción‐Alvarez, Javier Palacios, and Chukwuemeka R. Nwokocha declare that they have no conflict of interest., (© 2020 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Mangifera indica Linn popularly known as mango is used in folk medicine to treat gastrointestinal disorders. The aim of this study was to identify the metabolomic composition of lyophilized extract of mango leaf (MIE), to evaluate the antioxidant activity on several oxidative stress systems (DPPH, FRAP, TBARS, and ABTS), the spasmolytic and antispasmodic activity, and intestinal protective effect on oxidative stress induced by H 2 O 2 in rat ileum. Twenty-nine metabolites were identified and characterized based on their ultra-high-performance liquid chromatography (UHPLC) high-resolution orbitrap mass spectrometry, these include: benzophenone derivatives, xanthones, phenolic acids, fatty acids, flavonoids and procyanidins. Extract demonstrated a high antioxidant activity in in-vitro assays. MIE relaxed ( p < 0.001) intestinal segments of rat pre-contracted with acetylcholine (ACh) (10 -5 M). Pre-incubation of intestinal segments with 100 µg/mL MIE significantly reduced ( p < 0.001) the contraction to H 2 O 2 . Similar effects were observed with mangiferin and quercetin (10 -5 M; p < 0.05) but not for gallic acid. Chronic treatment of rats with MIE (50 mg/kg) for 28 days significantly reduced ( p < 0.001) the H 2 O 2 -induced contractions. MIE exhibited a strong antioxidant activity, spasmolytic and antispasmodic activity, which could contribute to its use as an alternative for the management of several intestinal diseases related to oxidative stress.

Melicoccus bijugatus Jacq (Mb) has been reported to have cardiovascular modulatory effects. In this study, we evaluated the antihypertensive effects and mechanism of action of Mb on N G -Nitro-L-arginine Methyl Ester (L-NAME) and Deoxycorticosterone Acetate (DOCA) rat models. Aqueous extract of Mb fruit (100 mg/kg) was administered for 6 weeks to rats by gavage and blood pressure was recorded. Effects of the extract on vascular reactivity was evaluated using isolated organ baths, and tissues were collected for biochemical and histological analysis. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly (P < 0.05) reduced with extract (100 mg/kg) administration and treatment compared to the hypertensive models. Mb (100 µg/mL) reduced the vascular contractility induced by phenylephrine (PE), and caused a dose-dependent relaxation of PE-induced contraction of aortic vascular rings. The vasorelaxation properties seemed to be endothelium dependent, as well as nitric oxide (NO) and guanylyl cyclase, but not prostaglandin dependent. Histomicrograph of transverse sections of the ventricles from the Mb group did not show abnormalities. The extract significantly (P < 0.05) reduced an L-NAME induced elevation of cardiac output and Creatine Kinase Muscle-Brain (CKMB), but had no significant impact on the activities of arylamine N-acetyltransferase. In conclusion, Mb significantly decreased blood pressure in hypertensive models. The extract possesses the ability to induce endothelium dependent vasodilation, which is dependent on guanylyl cyclase but not prostaglandins.

Heliotropium taltalense is an endemic species of the northern coast of Chile and is used as folk medicine. The polyphenolic composition of the methanolic and aqueous extract of the endemic Chilean species was investigated using Ultrahigh-Performance Liquid Chromatography, Heated Electrospray Ionization and Mass Spectrometry (UHPLC-Orbitrap-HESI-MS). Fifty-three compounds were detected, mainly derivatives of benzoic acid, flavonoids, and some phenolic acids. Furthermore, five major compounds were isolated by column chromatography from the extract, including four flavonoids and one geranyl benzoic acid derivative, which showed vascular relaxation and were in part responsible for the activity of the extracts. Since aqueous extract of H. taltalense (83% ± 9%, 100 μg/mL) produced vascular relaxation through an endothelium-dependent mechanism in rat aorta, and the compounds rhamnocitrin (89% ± 7%; 10 -4 M) and sakuranetin (80% ± 6%; 10 -4 M) also caused vascular relaxation similar to the extracts of H. taltalense , these pure compounds are, to some extent, responsible for the vascular relaxation.

Background: Implant-based immediate approach remains to be a first line option for reconstruction of mastectomy defects. When combined with post-mastectomy radiation therapy (PMRT) two different schemas are possible: radiating the temporary tissue expander (TTE) or the permanent implant (PI). The present article intends to be the biggest cohort meta-analysis to the date comparing reconstructive failure (RF) rate in these two scenarios: PMRT to TE compared with PMRT to PI., Methods: A systematic search of the literature was performed on PUBMED/MEDLINE. The following key words were chosen: Breast Reconstruction AND Implant based AND Immediate. The time limit applied was from January 2008 to January 2019. We selected ten articles (n=1,130) to perform a meta-analysis due to the similarity of their approaches. Secondly, we did a simple literature review in order to identify some variables possibly working as predicting factors for RF., Results: Previous meta-analysis are analysed. Some variables possibly working as risk factors for RF are summarized. We performed a meta-analysis in two scenarios: a fixed-effect model and a random effect model. For the random effect model an OR of 1.85 was obtained (0.96, 3.57; P=0.067). A funnel plot is performed showing no publication bias exists., Conclusions: There is a tendency towards a higher RF rate when the TTE is irradiated compared with the irradiation of the PI. Further studies trying to elucidate the influence of the suggested risk factors for RF have to be performed to stablish a consensus about the indications and contraindications of this reconstructive modality., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.01.20). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

The infusion of the desertic plant Nolana ramosissima I.M. Johnst showed vascular smooth muscle relaxation in rat aorta and the presence of several phenolic compounds, which were detected by high resolution UHPLC-Orbitrap-HESI-MS. In addition, five flavonoids were rapidly isolated from a methanolic extract using high-performance counter-current chromatography (HPCCC). The N. ramosissima extract showed endothelium-independent relaxation effect in rat aorta. Sixty-one compounds were detected in the infusion, mainly glycosylated flavonoids, flavanones and several oxylipins, suggesting that a synergistic effect between the compounds in the extracts could be responsible for the relaxation activity. Vascular activity experiments were done in isolated organ bath. In rat aorta, a nitric oxide inhibitor did not prevent the relaxation effects of the extract; however, a selective guanylyl cyclase inhibitor partially blunted this effect. The compound 5 ,3'-dihydroxy-4'7-dimethoxyflavone presented higher relaxation effect than 100 μg/mL of N. ramosissima extract. The extract and the isolated metabolites from N. ramosissima can show relaxation effects on rat aorta by a mechanism that is independent of the endothelium.

Parastrephia quadrangularis (Pq), commonly called "Tola", is widely used in folk medicine in the Andes, including for altitude sickness. In this study, polyphenolic composition was determined, and hypotensive effects were measured; the ethnopharmacological use as hypotensive was related to the presence of phenolic compounds. For this purpose, male Sprague-Dawley rats (6 to 8 weeks of age, 160 to 190 g) were fed Pq extract (10 to 40 mg/kg) for 10 days through gavage. Blood pressures and heart rate were significantly ( p < 0.01) reduced in normotensive rats receiving Pq extract (40 mg/kg body weight). Pq extract induced a negative inotropic effect, and endothelium-dependent vasodilation mediated by nitric oxide (NO). Furthermore, preincubation with Pq extract significantly decreased the cytosolic calcium on vascular smooth muscle cells A7r5 in response to L-phenylephrine (PE). Seven metabolites were isolated from the Pq extract, but three flavonoids (10 -4 M) showed similar vasodilation to the extract in intact rat aorta as follows: 5,3',4'-trihydroxy-7-methoxyflavanone (2); 3,5,4'-trihydroxy-7,8,3'-trimethoxyflavone (6); and 5,4'-dihydroxy-3,7,8,3'-tetramethoxyflavone (7). The Pq extract and compounds 2 and 7 significantly ( p < 0.05) reduced the contraction to Bay K8644 (10 nM, an agonist of Ca V 1.2 channels). Administration of Pq decreased cardiac contractility and increased endothelium-dependent and -independent vasodilation.

Background Gongronema latifolium Benth. (family Apocynaceae) leaves (GL) has interesting medicinal properties. The effects of extracts from G. latifolium on blood pressure (BP) and the possible mechanisms of action were also investigated. Methods The ultrahigh resolution liquid chromatography orbitrap MS analysis was used to identify the phytochemicals present. Normotensive Wistar rats were anesthetized with sodium pentobarbitone (40 mg/kg) intraperitoneally, and the jugular vein was cannulated for infusion of drugs while the carotid artery was cannulated for direct BP measurement. GL extract (5-20 mg) alone or with nifedipine (10 mg/kg), atropine (2 mg/kg), L-NAME (5 mg/kg), methyl blue (3 mg/kg) and propranolol (1 mg/kg) were administered intravenously to Wistar rats and direct BP measurements were carried out. Results Systolic and diastolic BP levels (128/90 mm Hg; MAP 103 ± 3 mm Hg) and heart rates were all significantly (p < 0.01) decreased after GL administration. Raised mean arterial pressure (MAP) and heart rate by atropine, L-NAME and methyl blue were significantly (p < 0.01) reduced after GL administration, while propranolol significantly (p < 0.01) inhibited hypotension caused by GL. Infusion of GL reduced MAP (95 ± 3 mm Hg) comparable with nifedipine (93 ± 2 mm Hg), a calcium channel blocker. The phytochemicals identified were 34 compounds, including oleanolic acid derivatives, flavonoids, antioxidant fatty acids, 2 coumarins and 2 iridoids. Conclusions These results suggest that G. latifolium has hypotensive properties mediated by the synergistic activity of the compounds, probably via the β-adrenergic blockade mechanism.

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl 2 (Kir), 10 μM glibenclamide (K ATP ), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly ( p < 0.05) reduced the ARI-induced relaxation. ARI significantly ( p < 0.05) reduced the contractile response to agonist of Ca V 1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.

Guinep is traditionally used in the management of cardiovascular ailments. This study aims to evaluate its medicinal constituents and effects in the management of myocardial injury in an experimental isoproterenol (ISO) rat model. Sprague-Dawley rats were randomly assigned to four groups: Group 1 was the control group; Group 2 received M. bijugatus extract (100 mg/Kg; MB) for six weeks; Group 3 was given ISO (85 mg/Kg) i.p. twice during a 24-hour period; and Group 4 was given ISO (85 mg/Kg) i.p. and MB extract (100 mg/Kg) for six weeks. The MB was administered orally by gavage, daily. The blood pressure of conscious animals was measured, while ECG was performed under anesthesia. Blood and serum were collected for biochemical and hematological analysis. The ISO group treated with MB showed a significant decrease ( p < 0.001) in (SBP), diastolic (DBP), mean arterial (MAP) and heart rate (HR) compared to the ISO only group. Conversely, MB treated rats that were not induced with ISO displayed a significant decreases ( p < 0.001) in SBP, DBP, MAP, and HR. ISO significantly elevated the ST segment ( p < 0.001) and shortened the QTc interval ( p < 0.05), which were recovered after treatment with 100 mg/Kg of MB. In addition, the results showed a significant decrease ( p < 0.001) in the heart to body weight ratio of the ISO group treated with MB compared to the ISO only group. Furthermore, the extract normalized the hematological values depressed by the ISO while significantly elevating the platelet count. UHPLC high-resolution orbitrap mass spectrometry analysis results revealed the presence of several antioxidants like vitamin C and related compounds, phenolic acids, flavonoid, fatty acids (oxylipins), and terpene derivatives. The results of this study indicated that Melicoccus bijugatus did display some cardio-protective effects in relation to myocardial injury.

Lymphedema is the result of an alteration of the lymphatic drainage, and its most common worldwide cause is filariasis. In our practice usually is associated to neoplasic, inflammatory and granulomatous processes, radiotherapy, hydroelectrolytic disbalances, and idiopathic. It can affect any part of the body, including the penis and scrotum. The genital lymphedema is a rare presentation, it corresponds to 0.6% of lymphedema. However, causes serious functional, social and emotional limitations for the patient. Too often have pain, recurrent infections, sexual dysfunction, cosmetic deformity, sometimes it limits mobility and ambulation. Although there are several treatment options, both medical and surgical, it has not been found ideal for this disease. We present a 43 years old patient with penoscrotal lymphedema due to hidradenitis suppurativa, it limits his normal activity. The patient was referred to our center after unsuccessful medical treatment (doxycycline and clindamycin cycles). Surgical treatment consisted of total excision of the skin and subcutaneous tissue to Buck's fascia. Split thickness skin grafts were used to cover the defect. The result was satisfactory both functionally and aesthetically., (Copyright: © 2019 Permanyer.)

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis . The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10 -6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10 -4 M) significantly reduced the contractile response to KCl ( p < 0.001) more than PE ( p < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10 -4 M) drastically reduced the contraction to KCl (6·10 -2 M), but after that, PE (10 -6 M) caused contraction ( p < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10 -5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 × 10 -3 M; p < 0.01) and BaCl₂ (a non-selective inward rectifier potassium channel blocker; 5 × 10 -3 M; p < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10 -5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10 -3 M; p < 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca 2+ in a Ca 2+ free solution ( p < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10 -8 M; p < 0.01), likely decreasing the influx of extracellular Ca 2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies.

Background: Xenophyllum poposum is an endemic species of the Andes Cordillera, popularly known as Popusa. Popusa is widely used by mountain communities as a folk medicine to treat altitude sickness and hypertension., Purpose: The aim of this study is to evaluate the hypotensive effects and vascular reactivity of Popusa extracts and its pure isolated compounds., Methods: Hydroalcoholic extract of Xenophyllum poposum (HAE X. poposum; 40 mg/kg dose) were administered to rats by gavage and mean arterial pressures were recorded. Organ bath studies were conducted in endothelium-intact and denuded rings, and the vascular reactivity of the HAE X. poposum extract and its isolated compounds were compared and analysed. Cytosolic Ca 2+ was measured in vascular smooth muscle cell line A7r5 using Fura2-AM., Results: HAE X. poposum significantly reduced the mean arterial blood pressure and heart rate in normotensive rats chronically treated with the extract, as well as mice acutely treated with the extract. A negative chronotropic effect was observed in the isolated rat heart. HAE X. poposum induced endothelial vasodilation mediated by nitric oxide (NO), reduced the contractile response to PE, and decreased PE-induced intracellular Ca 2+ influx in vascular smooth muscle cells. Pure compounds isolated from HAE X. poposum such as 4‑hydroxy‑3-(3-methyl-2-butenyl) acetophenone, 5-acetyl-6‑hydroxy‑2-isopropenyl-2, and 3-dihydrobenzofurane (dihydroeuparin) also triggered endothelium-dependent vasodilation., Conclusion: HAE X. poposum decreases blood pressure, heart rate and vascular response. The vasodilation properties of HAE X. poposum extract and its isolated compounds may act through the endothelial nitric oxide synthase, as well as calcium channel blocker mechanisms. The results of the present study provide the first qualitative analysis that supports the use of X. poposum in traditional folk medicine for the treatment of altitude sickness and hypertension., (Copyright © 2018. Published by Elsevier GmbH.)

Quinone derivatives like 2-(4-hydroxyphenyl) amino-1,4-naphthoquinone (Q7) are used as antitumor agents usually associated with adverse effects on the cardiovascular system. The objective of this study was to evaluate the cardioprotective effect of ascorbate on Q7-induced cardiovascular response in Wistar rats. In this study, blood pressure, vascular reactivity, and intracellular calcium fluxes were evaluated in cardiomyocytes and the rat aorta. We also measured oxidative stress through lipid peroxidation (TBARS), superoxide dismutase- (SOD-) like activity, and H 2 O 2 generation. Oral treatment of rats with ascorbate (500 mg/kg) for 20 days significantly ( p < 0.05) reduced the Q7-induced increase (10 mg/kg) in blood pressure and heart rate. The preincubation with ascorbate (2 mM) significantly ( p < 0.05) attenuated the irregular beating of the atrium induced by Q7 (10 -5  M). In addition, ascorbate induced endothelial vasodilation in the presence of Q7 in the intact aortic rings of a rat and reduced the cytosolic calcium levels in vascular smooth muscle cells. Ascorbate also reduced the Q7-induced oxidative stress in vivo . Ascorbate also attenuated Q7-induced SOD-like activity and increased TBARS levels. These results suggest a cardioprotective effect in vivo of ascorbate in animals treated orally with a naphthoquinone derivative by a mechanism involving oxidative stress.

Lymphedema is the result of an alteration of the lymphatic drainage, and its most common worldwide cause is filariasis. In our practice usually is associated to neoplasic, inflammatory and granulomatous processes, radiotherapy, hydroelectrolytic disbalances, and idiopathic. It can affect any part of the body, including the penis and scrotum. The genital lymphedema is a rare presentation, it corresponds to 0.6% of lymphedema. However, causes serious functional, social and emotional limitations for the patient. Too often have pain, recurrent infections, sexual dysfunction, cosmetic deformity, sometimes it limits mobility and ambulation. Although there are several treatment options, both medical and surgical, it has not been found ideal for this disease. We present a 43 years old patient with penoscrotal lymphedema due to hidradenitis suppurativa, it limits his normal activity. The patient was referred to our center after unsuccessful medical treatment (doxycycline and clindamycin cycles). Surgical treatment consisted of total excision of the skin and subcutaneous tissue to Buck's fascia. Split thickness skin grafts were used to cover the defect. The result was satisfactory both functionally and aesthetically., (Copyright: © 2018 Permanyer.)

Ethnopharmacological Relevance: The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats., Material and Methods: Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-h period. Blood pressure readings were taken before and after the administering of ISO using the tail cuff method. ECG was performed on anaesthetized rats. Cardiac contractility was measured in isolated right atrial muscles. Assessment of myocardial infarct (MI) size, heart/body weight ratio, biochemical, hematological and histo-morphological parameters were conducted at the end of seven days. An aqueous extract from leaves of A. altilis was analyzed for organic compounds using UHPLC mass spectrometry., Results: ISO induced myocardial damage through an elevation of the heart rate (HR), infarct size and ECG distortions. Treatment with AA significantly (p˂0.05) reduced heart/body weight ratio (49%), MI (96%), HR (27%), sympathovagal imbalance (36%) and serum cardiac biomarkers (AST, LDH, HDL, triglycerides and CCK) caused by ISO. AA decreased the beat frequency of isolated right atrium (11%) cause by ISO, an action similar to propranolol (beta-adrenergic antagonist; 20%), but showed no significant changes in the QTc intervals of the ECG (suggesting no cardio-toxic drug-herb interactions), Thirty nine compounds were detected using high resolution LC-MS analysis (HPLC-Orbitrap-APCI-MS) in the extract. Pure compounds, as gallic acid and rutin, presented a higher negative chronotropic effect, similar to propranolol., Conclusion: Oral administration of aqueous extract of Artocarpus artilis has cardio-protective functions in myocardial injury, in part, by decreasing the HR, reduced contractility and infarct size. These findings may explain the cardio-protective use of A. altilis in traditional medicine., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Tech-Check-Tech (TCT) allows a pharmacy technician to perform the final check of medications prepared by another technician. The effect of a TCT program on the time required to process medications in a hospital pharmacy has not been previously reported. Objective: To evaluate the effect of implementing a TCT program on the time required to prepare, check, and deliver medications to automated medication supply systems (AMSS) located throughout an academic medical center. Methods: The primary outcome was the difference in mean total time required to process AMSS medications between pre- and post-implementation periods. Forty-five days pre-TCT implementation was compared to 45 days post implementation. To assess the effect of the TCT program on pharmacist-time allocation, median times required to verify stat and routine medication orders in the computerized physician order entry (CPOE) system were analyzed. Results: Mean total time spent processing AMSS medications was 24.16 ± 2.98 hours and 16.79 ± 2.65 hours for the pre- and post-TCT implementation periods, respectively (difference of 7.37 hours; 95% CI, 6.19-8.55 hours; p < 0.0001). Median verification times for stat medication orders were 5 (interquartile range [IQR], 2-12) minutes before and 4 (IQR, 2-9) minutes after TCT implementation ( p < 0.0001). For routine orders, median verification times were 12 (IQR, 4-30) minutes before and 7 (IQR, 3-18) minutes after implementation ( p < 0.0001). Conclusions: The total time required to process AMSS medications was significantly reduced after a TCT program was implemented in an academic medical center. Pharmacist medication order verification times were also significantly reduced.

Ethnopharmacological Relevance: Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats., Material and Methods: Seven compounds were isolated from the HAE S. nutans, and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans-dependent vasodilation and phenylephrine-dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats., Results: Seven pure compounds were isolate from HAE S. nutans, but two pure compounds showed significant vasodilation in rat aorta: 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E) and 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane (compound G). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium-intact, but not in endothelium-denuded aortic rings., Conclusion: HAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Drug permeation through skin, or a synthetic membrane, from locally acting pharmaceutical products can be influenced by the permeation behaviour of pharmaceutical excipients., Objective: Terahertz time-domain technology is investigated as a non-invasive method for a direct and accurate measurement of excipients permeation through synthetic membranes or human skin., Methods: A series of in-vitro release and skin permeation experiments of liquid excipients (e.g. propylene glycol and polyethylene glycol 400) has been conducted with vertical diffusion cells. The permeation profiles of excipients through different synthetic membranes or skin were obtained using Terahertz pulses providing a direct measurement. Corresponding permeation flux and permeability coefficient values were calculated based on temporal changes of the terahertz pulses., Results: The influence of different experimental conditions, such as the polarity of the membrane and the viscosity of the permeant, was assessed in release experiments. Specific transmembrane flux values of those excipients were directly calculated with statistical differences between cases. Finally, an attempt to estimate the skin permeation of propylene glycol with this technique was also achieved. All these permeation results were likely comparable to those obtained by other authors with usual analytical techniques., Conclusion: Terahertz time-domain technology is shown to be a suitable technique for an accurate and non-destructive measurement of the permeation of liquid substances through different synthetic membranes or even human skin., (© 2016 Royal Pharmaceutical Society.)

Ethnopharmacological Relevance: Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America used in the management of acute mountain sickness in the Andean communities. Currently, the direct effects of hydroalcoholic extract from S. nutans on the cardiovascular system are unknown. The aim of this study was to determine the effects and mechanism of action of S. nutans on cardiovascular function in normotensive and Angiotensin II (1μg/mL) hypertension mice models., Material and Methods: Blood pressure and ECG measurements were simultaneously carried out on the mice and rats. The isolated right atrium, papillary muscle of the left ventricle and isolated heart of rat were used to study the cardiac functions and mechanisms., Results: S. nutans (40mg/Kg) induced a 30% and 12% significant (p<0.05) reduction of the mean arterial pressure (MAP) in normotensive and hypertensive mice respectively. This decrease was as a result of decrease in heart rate (HR) in normotensive (25%) and hypertensive model (31%). It also decreased the sinus rhythm in isolated right atrium of rat. Compared with Losartan, a known anti-hypertensive, S. nutans caused a dose-dependent negative inotropic effect (dP/dtmax) on Langendorff isolated heart system. While Losartan, decreased the MAP by 30% but had no effect on heart rate. The calcium blocker nifedipine had similar effects as S. nutans, decreasing the beat frequency of isolated right atrium and contractility of papillary muscle of the left ventricle of rat., Conclusion: The results suggest an important clinical function in hypertension therapy, as S. nutans could decrease the blood pressure in hypertensive mice by decreasing the HR and contractility, leading to a reduction in myocardial oxygen demand., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This is the first study where graphene is used as a MALDI adjuvant in combination with the traditional matrix α-cyano-4-hydroxycinnamic acid (CHCA) to improve the signal intensity of peptide samples. Use of this amended matrix not only leads to increased signals but also to a higher number of peaks detected in complex samples. Additionally, the use of graphene has a stabilizing effect that can also be exploited to improve the detection of easily cleavable molecules. Graphical Abstract ᅟ.

The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7 , a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl 2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl 2 (10 -3  M), an inward rectifying K + channels blocker, and blocked the vasodilation to KCl (10 -2  M) in aortic rings precontracted with BaCl 2 . This was recovered with sodium nitroprusside (10 -8  M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K + channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.

Arsenic trioxide (As2O3) is used clinically in the management of acute promyelocytic leukemia, and the use of electrocardiogram (ECG) in this management is important as arsenic use may cause distortion of the electrical properties with its attendant sequel. We studied the effect of As2O3 on vasomotion in rat aortic rings using isometric tension recordings and ECG in anesthetized rats. The results showed that As2O3 (10(-5) M) significantly (p < 0.01) reduced the frequency of acetylcholine (10(-5) M ACh)- and KCl (10 mM)-induced vasomotion, and it also increased the relaxation time (R t) of vasomotion. This effect was restored by 10(-8) M sodium nitroprusside (nitric oxide donor). ACh-induced NO release in the aorta was blunted in the presence of As2O3. The corrected QT interval (QTc) of the ECG, and time dilation (T d) of the pulse wave in the tail artery of the anesthetized rat were significantly (p < 0.05) increased in the arsenic-treated group (50 ppb As) versus control. In conclusion, data suggest that arsenic-induced reduction in vasomotion frequency of the isolated aortic rings is associated with a decreased bioavailability of NO, an increase in QTc and a decrease in the frequency of the pulse wave generated by the cardiac cycle in anesthetized rats.

Vasomotion is defined as the rhythmic contractions in blood vessels, consisting of two components: vasoconstriction and oscillations of the plasma membrane potential. To determine whether vasomotion is associated with changes in K(+) uptake, we measured the effect of phenylephrine (PE) and acetylcholine (ACh) on the K(+) uptake and vascular reactivity in rat aortic rings. We found that the incubation of aortic rings with 10(-7) M PE (210 ± 28 mg maximum amplitude), and 10(-6) M ACh (177 ± 6 mg maximum amplitude) produced the highest rhythmic contractions. Both 10(-7) M PE and 10(-6) M ACh significantly increased K(+) uptake in endothelium-intact aorta versus control (121 % PE, 117 % ACh). Removal of the endothelium blunted rhythmic contractions and decreased K(+) uptake in presence of vasoactive substances (88 % PE, 81 % ACh). The inhibition of nitric oxide synthase with 10(-4) M L-NNA significantly reduced the rhythmic contractions, and it was reversed in the presence of 10(-8) M sodium nitroprusside (SNP; a nitric oxide donor). Also, we found that 10(-4) M L-NNA significantly decreased the effect of 10(-7) M PE on K(+) uptake in aortic rings (104 % PE + L-NNA vs. control). The incubation of endothelium-denuded rings with 10(-8) M SNP significantly increased the K(+) uptake (116 % SNP vs. control), similar to those observed in the presence of 10(-6) M ACh. The inhibition of protein kinase G with KT-5823 blocked SNP-mediated increase in K(+) uptake. In conclusion, these data suggest that a certain range of K(+) uptake is necessary to induce the rhythmic contractions in response to vasoactive substances.

Populations chronically exposed to arsenic in drinking water often have increased prevalence of diabetes mellitus. The purpose of this study was to compare the glucose homeostasis of male and female rats exposed to low levels of heavy metals in drinking water. Treated groups were Sprague-Dawley male and female rats exposed to drinking water from Antofagasta city, with total arsenic of 30 ppb and lead of 53 ppb for 3 months; control groups were exposed to purified water by reverse osmosis. The two treated groups in both males and females showed arsenic and lead in the hair of rats. The δ-aminolevulinic acid dehydratase was used as a sensitive biomarker of arsenic toxicity and lead. The activity of δ-aminolevulinic acid dehydratase was reduced only in treated male rats, compared to the control group. Treated males showed a significantly sustained increase in blood glucose and plasma insulin levels during oral glucose tolerance test compared to control group. The oral glucose tolerance test and the homeostasis model assessment of insulin resistance demonstrated that male rats were insulin resistant, and females remained sensitive to insulin after treatment. The total cholesterol and LDL cholesterol increased in treated male rats vs. the control, and triglyceride increased in treated female rats vs. the control. The activity of intestinal Na+/glucose cotransporter in male rats increased compared to female rats, suggesting a significant increase in intestinal glucose absorption. The findings indicate that exposure to low levels of arsenic and lead in drinking water could cause gender differences in insulin resistance.

A new integrated 3-zone simulated moving bed (SMB) concept with internal racemization reaction was suggested recently for the production of single enantiomers from racemic mixtures [1,2]. The process utilizes an internal gradient to trigger the racemization within a single zone. It can deliver the pure enantiomer and outperforms conventional technologies. In this contribution, the concept is validated experimentally for the separation of a model system compound. The results demonstrate that the new concept is capable of producing a single enantiomer with purity, yield and conversion of 100%., (Copyright © 2011 Elsevier B.V. All rights reserved.)