A new oxime synthesized from Senecio nutans SCh. Bip (chachacoma) reduces calcium influx in the vascular contractile response in rat aorta.

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 (EC50) 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 Ca2+ induced by KCl. 2,3-Dihydrobenzofurane derived from S. nutans (Sn-I) reduces the contractile response probably by blocking Ca2+ entry through voltage-gated Ca2+ channels (VGCC) in vascular smooth cells. This effect also causes relaxation in rat aorta mediated by reduction of intracellular Ca2+ concentration, rather than an increase of NO generation in endothelial vascular cells.

Chemical Characterization of Phoenix dactylifera L. Seeds and their Beneficial Effects on the Vascular Response in Hypertensive Rats.

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-Nω-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.

Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens.

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 Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ 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 Ca2+ uniporter (MCU) enhance Ca2+-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 Ca2+ 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-α1C (CaV1.2), Na+-K+-2Cl- symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ 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 Ca2+ signaling mean both sexes ought to be included in experimental design.

Superficial lateral arm flap for post-burn antecubital contractures.

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.

Celulitis necrosante estéril en las extremidades de migrantes marinos tras travesías prolongadas / Sterile necrotizing cellulitis in boat immigrants’ limbs after long journeys across the ocean

Fundamento Las Islas Canarias reciben migrantes de origen subsahariano que llegan a la costa tras largas travesías marinas en condiciones adversas. El «pie de patera» es una entidad previamente descrita consistente en un cuadro clínico desarrollado a partir de heridas en los pies que se infectan por estar en contacto con aguas fecales estancadas en el fondo de estas embarcaciones. Describimos un nuevo cuadro clínico, hasta ahora no publicado, consistente en un edema masivo de las extremidades que asocia necrosis de la piel y del tejido celular subcutáneo, respeta el músculo y su etiología no es de origen infeccioso. Material y métodos Diseñamos un estudio descriptivo observacional entre los meses de septiembre del año 2020 y enero del año 2022, ambos incluidos, en el ámbito del hospital de tercer nivel situado en Gran Canaria. Se incluyeron un total de 86 pacientes en una base de datos donde se analizaron 39 variables cualitativas y cuantitativas. Resultados Un total de 16 pacientes desarrollaron el cuadro consistente en una celulitis necrosante estéril. Su fisiopatogenia difiere de la del pie de patera, ya que en todos los casos los cultivos resultan estériles. Conclusiones Como mecanismo responsable, postulamos una teoría inflamatoria derivada del efecto osmótico de la ingesta de agua de mar y/o la reposición agresiva de fluidos a su llegada a los centros hospitalarios donde ingresan con deshidrataciones hipernatrémicas graves. El tratamiento quirúrgico precoz consiste en evacuar el edema mediante incisiones tipo escarotomías, el cual alivia la sintomatología y previene la progresión del cuadro (AU)

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 (AU)

Sterile necrotizing cellulitis in boat immigrants' limbs after long journeys across the ocean. / Celulitis necrosante estéril en las extremidades de migrantes marinos tras travesías prolongadas.

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 foot¼ 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 («patera¼) 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.

Chemical Fingerprinting, Aorta Endothelium Relaxation Effect, and Enzymatic Inhibition of Canelo (Drimys winteri J. R. Forst. & G. Forst, (D.C) A. Gray, Family Winteraceae) Fruits.

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 (IC50 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 (IC50: 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.

Identification of phytochemicals and assessment of hypoglycemic and haematological potentials of Terminalia catappa Linn leaf extract in alloxan-induced diabetic Wistar rats.

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.

UHPLC-MS Phenolic Fingerprinting, Aorta Endothelium Relaxation Effect, Antioxidant, and Enzyme Inhibition Activities of Azara dentata Ruiz & Pav Berries.

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 IC50: 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC50: 6.73 + 0.07 µg extract/mL, amylase IC50: 5.6 ± 0.0 µg extract/mL, lipase IC50: 30.8 ± 0.0 µg extract/mL, and tyrosinase IC50: 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.

A hydroalcoholic extract of Senecio nutans SCh. Bip (Asteraceae); its effects on cardiac function and chemical characterization.

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 [Ca2+]i transient amplitude and sarcomere shorting by 40 and 49% (p < 0.001), respectively. The amplitude of the caffeine evoked [Ca2+]i transient was reduced by 24% (p < 0.001), indicating reduced sarcoplasmic reticulum (SR) Ca2+ content. Sodium-calcium exchanger (NCX) activity increased by 17% (p < 0.05), while sarcoendoplasmic reticulum Ca2+-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 Ca2+ content. These results highlight the plant's potential as a source of novel cardio-active phytopharmaceuticals or nutraceuticals.

Enfermedad de Kimura en paciente no asiática / Kimura’s disease in a non-asian patient

La enfermedad de Kimura es un trastorno inflamatorio benigno poco frecuente, de etiología desconocida y que afecta principalmente a sujetos de origen asiático. Clínicamente se manifiesta como masas subcutáneas, indoloras, sobre todo en la zona de cabeza y el cuello. Suele acompañarse de linfadenopatías, y aumento de los niveles de eosinófilos e IgE en sangre periférica. Se presenta un caso de enfermedad de Kimura, diagnosticado en una mujer caucásica tras la exéresis-biopsia de una masa mandibular de gran tamaño. Describir esta patología ayudará a incluir la misma en el diagnóstico diferencial de masas, sobre todo a nivel cervico-facial, favoreciendo así su adecuado manejo diagnóstico-terapéutico. (AU)

Kimura’s disease is a rare benign inflammatory disorder of unknown etiology that mainly affects individuals of Asian origin. Clinically it manifests as subcutaneous, painless masses, especially in the head and neck area. It is usually accompanied by lymphadenopathies and an increase in eosinophil and IgE levels in peripheral blood. A case of Kimura’s disease is presented, diagnosed in a Caucasian woman after the excision-biopsy of a large mandibular mass. Describing this pathology will help to include it in the differential diagnosis of masses, especially at the cervico-facial area, thus favoring its adequate diagnostic-therapeutic management. (AU)

Phenolic Fingerprinting and Bioactivity Profiling of Extracts and Isolated Compounds from Gypothamnium pinifolium Phil.

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 (IC50: 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) IC50: 23.44 ± 0.03 µg/mL) and tyrosinase (IC50: 9.25 ± 0.15 µg/mL) enzymes of the n-hexane extract, and main compounds (IC50: 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.

Rural-urban gradients and all-cause, cardiovascular and cancer mortality in Spain using individual data.

•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.

Lepidium meyenii Walp (red maca) Supplementation Prevents Acrylamide-Induced Oxidative Stress and Liver Toxicity in Rats: Phytochemical Composition by UHPLC-ESI-MS/MS.

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.

Oxidant-induced disruption of vascular K+ channel function: Implications for diabetic vasculopathy.

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.

Novel Oxime Synthesized from a Natural Product of Senecio nutans SCh. Bip. (Asteraceae) Enhances Vascular Relaxation in Rats by an Endothelium-Independent Mechanism.

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.

Artocarpus Altilis (Breadfruit) could Reverse Myocardial Infarction Through the Normalization of the Oxygen Haemoglobin Dissociation Curve.

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.

Oncological outcomes of lipofilling in breast reconstruction: a matched cohort study with 250 patients.

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.

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