LA ANGIOGÉNESIS ES UN PROCESO CLAVE POR EL CUAL SE FORMAN NUEVOS VASOS SANGUÍNEOS CAPILARES, MANTENIENDO EL SUMINISTRO DE OXÍGENO Y OTROS NUTRIENTES AL CUERPO, PERMITIENDO SU CRECIMIENTO Y CURACIÓN DE HERIDAS, ENTRE OTROS. SIN EMBARGO, LA ANGIOGÉNESIS TAMBIÉN SE ASOCIA CON PROCESOS PATOLÓGICOS, TALES COMO EL CRECIMIENTO DE TUMORES. LAS CÉLULAS ENDOTELIALES VASCULARES PRODUCEN DIFERENTES ENZIMAS DE REMODELACIÓN DE LA MATRIZ, TALES COMO LAS METALOPROTEINASAS DE LA MATRIZ Y LA A-DESINTEGRINA Y LAS METALOPROTEINASAS, QUE TIENEN EFECTOS POSITIVOS Y NEGATIVOS SOBRE LA ANGIOGÉNESIS, REGULANDO EL ENTORNO CELULAR Y LA SEÑALIZACIÓN. SIN EMBARGO, SE SABE POCO SOBRE LA REGULACIÓN DE LA ACTIVIDAD DE ESTAS PROTEASAS DURANTE EL DESARROLLO VASCULAR. LA PROTEÍNA RICA EN CISTEÍNA INDUCTORA DE REVERSIÓN CON MOTIVOS DE KAZAL (RECK) ES UN INHIBIDOR ANCLADO EN MEMBRANA DE DIFERENTES METALOPROTEINASAS DE MATRIZ Y UNA DESINTEGRINA Y METALOPROTEINASAS, SIENDO UN REGULADOR CRÍTICO DE LA REMODELACIÓN DE LA MATRIZ EXTRACELULAR Y LA VÍA DE SEÑALIZACIÓN, EN PARTICULAR NOTCH, QUE ES CRÍTICO PARA LA MADURACIÓN DE LOS VASOS EN CRECIMIENTO. RECK KNOCKOUT RATONES MUEREN EN EL ÚTERO MOSTRANDO DEFECTOS DE DESARROLLO VASCULAR Y HEMORRAGIAS MASIVAS. ESTOS DEFECTOS NO SE OBSERVARON EN RATONES KNOCKOUT PARA INHIBIDORES DE METALOPROTEINASAS DE MATRIZ SOLUBLE SECRETADAS QUE APUNTABAN A UN PAPEL EXCLUSIVO DE RECK EN EL DESARROLLO VASCULAR Y MADURACIÓN DESDE SU LOCALIZACIÓN EN LA MEMBRANA PLASMÁTICA. A PESAR DE LO ANTERIOR, EL PAPEL EXACTO DE RECK EN ESTE PROCESO NO HA SIDO ACLARADO. ESTA REVISIÓN SE CENTRA EN RESUMIR LA INFORMACIÓN DISPONIBLE SOBRE EL PAPEL DE RECK COMO MEMBRANA MEMBRANA MATRIZ DE LAS METALOPROTEINASAS Y UNA DESINTEGRINA Y METALOPROTEINASAS INHIBIDO

ADENOSINE IS AN ENDOGENOUS NUCLEOSIDE WITH PLEIOTROPIC EFFECTS IN DIFFERENT PHYSIOLOGICAL PROCESSES INCLUDING CIRCULATION, RENAL BLOOD FLOW, IMMUNE FUNCTION, OR GLUCOSE HOMEOSTASIS. CHANGES IN ADENOSINE MEMBRANE TRANSPORTERS, ADENOSINE RECEPTORS, AND CORRESPONDING INTRACELLULAR SIGNALLING NETWORK ASSOCIATE WITH DEVELOPMENT OF PATHOLOGIES OF PREGNANCY, INCLUDING PREECLAMPSIA. PREECLAMPSIA IS A CAUSE OF MATERNAL AND PERINATAL MORBIDITY AND MORTALITY AFFECTING 3-5% OF PREGNANCIES. SINCE THE PROPOSED MECHANISMS OF PREECLAMPSIA DEVELOPMENT INCLUDE ADENOSINE-DEPENDENT BIOLOGICAL EFFECTS, ADENOSINE MEMBRANE TRANSPORTERS AND RECEPTORS, AND THE ASSOCIATED SIGNALLING MECHANISMS MIGHT PLAY A ROLE IN THE PATHOPHYSIOLOGY OF PREECLAMPSIA. PREECLAMPSIA ASSOCIATES WITH INCREASED ADENOSINE CONCENTRATION IN THE MATERNAL BLOOD AND PLACENTAL TISSUE, LIKELY DUE TO LOCAL HYPOXIA AND ISCHEMIA (ALTHOUGH NOT DIRECTLY DEMONSTRATED), MICROTHROMBOSIS, INCREASED CATECHOLAMINE RELEASE, AND PLATELET ACTIVATION. IN ADDITION, ABNORMAL EXPRESSION AND FUNCTION OF EQUILIBRATIVE NUCLEOSIDE TRANSPORTERS IS DESCRIBED IN FOETOPLACENTAL TISSUES FROM PREECLAMPSIA; HOWEVER, THE ROLE OF ADENOSINE RECEPTORS IN THE AETIOLOGY OF THIS DISEASE IS NOT WELL UNDERSTOOD. ADENOSINE RECEPTORS ACTIVATION MAY BE RELATED TO ABNORMAL TROPHOBLAST INVASION, ANGIOGENESIS, AND ISCHEMIA/REPERFUSION MECHANISMS IN THE PLACENTA FROM PREECLAMPSIA.

GESTATIONAL DIABETES MELLITUS (GDM) IS A DETRIMENTAL CONDITION FOR HUMAN PREGNANCY ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION AND ENDOTHELIAL INFLAMMATION IN THE FETOPLACENTAL VASCULATURE AND LEADS TO INCREASED CARDIO-METABOLIC RISK IN THE OFFSPRING. IN THE FETOPLACENTAL VASCULATURE, GDM IS ASSOCIATED WITH ALTERED ADENOSINE METABOLISM. ADENOSINE IS AN IMPORTANT VASOACTIVE MOLECULE AND IS AN INTERMEDIARY AND FINAL PRODUCT OF TRANSMETHYLATION REACTIONS IN THE CELL. ADENOSINE KINASE IS THE MAJOR REGULATOR OF ADENOSINE LEVELS. DISRUPTION OF THIS ENZYME IS ASSOCIATED WITH ALTERATIONS IN METHYLATION-DEPENDENT GENE EXPRESSION REGULATION MECHANISMS, WHICH ARE ASSOCIATED WITH THE FETAL PROGRAMMING PHENOMENON. HERE WE PROPOSE THAT CELLULAR AND MOLECULAR ALTERATIONS ASSOCIATED WITH GDM CAN DYSREGULATE ADENOSINE KINASE LEADING TO FETAL PROGRAMMING IN THE FETOPLACENTAL VASCULATURE. THIS CAN CONTRIBUTE TO THE CARDIO-METABOLIC LONG-TERM CONSEQUENCES OBSERVED IN OFFSPRING AFTER EXPOSURE TO GDM.

INSULIN RESISTANCE IS CHARACTERISTIC OF PREGNANCIES WHERE THE MOTHER SHOWS METABOLIC ALTERATIONS, SUCH AS PREECLAMPSIA (PE) AND GESTATIONAL DIABETES MELLITUS (GDM), OR ABNORMAL MATERNAL CONDITIONS SUCH AS PREGESTATIONAL MATERNAL OBESITY (PGMO). INSULIN SIGNALLING INCLUDES ACTIVATION OF INSULIN RECEPTOR SUBSTRATES 1 AND 2 (IRS1/2) AS WELL AS SRC HOMOLOGY 2 DOMAIN-CONTAINING TRANSFORMING PROTEIN 1, LEADING TO ACTIVATION OF 44 AND 42 KDA MITOGEN-ACTIVATED PROTEIN KINASES AND PROTEIN KINASE B/AKT (AKT) SIGNALLING CASCADES IN THE HUMAN FOETOPLACENTAL VASCULATURE. PE, GDM, AND PGMO ARE ABNORMAL CONDITIONS COURSING WITH REDUCED INSULIN SIGNALLING, BUT THE POSSIBILITY OF THE INVOLVEMENT OF SIMILAR CELL SIGNALLING MECHANISMS IS NOT ADDRESSED. THIS REVIEW AIMED TO DETERMINE WHETHER REDUCED INSULIN SIGNALLING IN PE, GDM, AND PGMO SHARES A COMMON MECHANISM IN THE HUMAN FOETOPLACENTAL VASCULATURE. INSULIN RESISTANCE IN THESE PATHOLOGICAL CONDITIONS RESULTS FROM REDUCED AKT ACTIVATION MAINLY DUE TO INHIBITION OF IRS1/2, LIKELY DUE TO THE INCREASED ACTIVITY OF THE MAMMALIAN TARGET OF RAPAMYCIN (MTOR) RESULTING FROM LOWER ACTIVITY OF ADENOSINE MONOPHOSPHATE KINASE. THUS, A DEFECTIVE SIGNALLING VIA AKT/MTOR IN RESPONSE TO INSULIN IS A CENTRAL AND COMMON MECHANISM OF INSULIN RESISTANCE IN THESE DISEASES OF PREGNANCY. IN THIS REVIEW, WE SUMMARISE THE CELL SIGNALLING MECHANISMS BEHIND THE INSULIN RESISTANCE STATE IN PE, GDM, AND PGMO FOCUSED IN THE AKT/MTOR SIGNALLING PATHWAY IN THE HUMAN FOETOPLACENTAL ENDOTHELIUM.

OBESITY AND TYPE 2 DIABETES MELLITUS (T2DM) ARE DISEASES ASSOCIATED WITH HYPERTENSION AND METABOLIC ALTERATIONS. A SIGNIFICANT GROUP OF PATIENTS PRESENT BOTH OBESITY AND T2DM, A CONDITION DEFINED AS DIABESITY. ONE OF THE METABOLIC FEATURES IN THESE CONDITIONS IS THE CLINICAL PRESENTATION OF INSULIN RESISTANCE. SEVERAL TISSUES, INCLUDING THE LIVER, SKELETAL MUSCLE, AND VASCULATURE, AND PATIENTS WITH T2DM, GESTATIONAL DIABETES, AND OBESITY SHOW INSULIN RESISTANCE. THE VASCULAR EFFECT OF INSULIN, INCLUDING VASODILATION, IS MAINLY MEDIATED BY THE GENERATION OF NITRIC OXIDE. SEVERAL MECHANISMS ARE PROPOSED TO ELUCIDATE THE ORIGIN OF INSULIN RESISTANCE; NEVERTHELESS, A COMMON FINDING IS THE ENDOTHELIAL DYSFUNCTION IN THESE DISEASES. ENDOTHELIAL CELLS FROM SUBJECTS WITH OBESITY SHOW REDUCED NITRIC OXIDE SYNTHESIS, AN EFFECT THAT IS UNALTERED BY INSULIN. INDIVIDUALS WITH T2DM SHOW A MISBALANCE BETWEEN THE SYNTHESIS, RELEASE, AND BIOLOGICAL ACTIONS OF VASODILATORS AND VASOCONSTRICTORS SUCH AS NITRIC OXIDE AND ENDOTHELIN-1. HOWEVER, WHETHER THESE MECHANISMS ARE INVOLVED IN THE VASCULAR ALTERATIONS SEEN IN PATIENTS WITH DIABESITY IS UNCLEAR. IN THIS REVIEW, WE DISCUSSED THE MODIFICATIONS ON INSULIN SIGNALLING, INSULIN RESISTANCE IN OBESITY AND T2DM, AND THE REPORTED CHANGES IN SIGNALLING PATHWAYS IN DIABESITY.

THE RELEASE OF PROTONS (H+) OCCURS VIA THE NA+/H+ EXCHANGER ISOFORM 1 (NHE1) LEADING TO A STABLE INTRACELLULAR PH (PHI) IN MDCK CELLS. CHRONIC INTAKE OF ARSENIC TRIOXIDE (ATO), IN THE DRINKING WATER, ASSOCIATED WITH HIGHER MORBIDITY AND MORTALITY IN NEOPLASTIC TISSUES. ATO INCREASED NHE1 EXPRESSION AND ACTIVITY, RESULTING IN INTRACELLULAR ALKALIZATION AND HIGHER MDCK CELLS PROLIFERATION. SINCE THE PRO-PROLIFERATIVE TRANSCRIPTION FACTOR ACTIVATOR PROTEIN 1 (AP-1) GETS ACTIVATED BY AL ALKALINE INTRACELLULAR PH, A PHENOMENON PARALLELED BY HIGHER NHES ACTIVITY, WE ASKED WHETHER ATO-INCREASED MDCK CELLS PROLIFERATION INVOLVES AP-1-DEPENDENT NHE1 ACTIVATION. CELLS WERE EXPOSED (48 H) TO ATO (0.05 ?MOL/L), SR11302 (1 ?MOL/L, AP-1 INHIBITOR), HOE-694 (100 NMOL/L, NHE1 INHIBITOR) AND EIPA (50 ?MOL/L, NHE1/NHE3 INHIBITOR) IN THE PRESENCE OF S3226 (10 ?MOL/L, NHE3 INHIBITOR), CONCANAMYCIN A (0.1 ?MOL/L, V-ATPASES INHIBITOR), AND SCHERING (10 ?MOL/L, H+/K+-ATPASE INHIBITOR). [3H]THYMIDINE INCORPORATION, CELL COUNTING, WOUND HEALING ASSAY, AND AP-1 ACTIVITY WERE DETERMINED. THE PHI WAS MEASURED IN CELLS PRE-LOADED (10 MIN) WITH 2,7-BICARBOXYETHYL-5,6-CARBOXYFLUORESCEIN ACETOXYMETHYL ESTER (12 MMOL/L) AND EXPOSED TO NH4CL (20 MMOL/L). BASAL PHI AND RECOVERY RATE (DPHI/DT), INTRACELLULAR BUFFER CAPACITY (?I) AND H+ FLUX (JH+) WERE DETERMINED. NHE1 PROTEIN ABUNDANCE WAS MEASURED BY WESTERN BLOTTING AND IMMUNOFLUORESCENCE. ATO INCREASED THE CELL GROWTH (1.5 FOLD), BASAL PHI (0.4 PHI UNITS), DPHI/DT (1.8 FOLD), JH+ (1.4 FOLD), AP-1 ACTIVITY AND NHE1 PROTEIN ABUNDANCE (1.3 FOLD). ATO ALSO INCREASED (1.5 FOLD) THE NUCLEAR/PERINUCLEAR NHE1 IMMUNOSIGNAL. SR11302 AND HOE-694 BLOCKED ATO EFFECTS. THUS, ATO-INCREASED PROLIFERATION RESULTED FROM AP-1-DEPENDENT NHE1 ACTIVATION IN MDCK CELLS.

THE AIM OF THIS INVESTIGATION WAS TO DETERMINE THE CONTENTS OF POLYCYCLIC AROMATIC HYDROCARBONS (PAHS), POLYCHLORINATED BIPHENYLS (PCBS), MINERALS, TRACE ELEMENTS AND BIOACTIVITY IN THE GASTROPOD RAPANA THOMASIANA, WHICH CAN BE USED AS AN ENVIRONMENTAL BIOINDICATOR ORGANISM. THE CHEMICAL DIFFERENCES BETWEEN RAPANA THOMASIANA FROM POLLUTED (RAPAPOL) AND NON-POLLUTED (RAPANPOL) SITES OF THE BLACK SEA COAST IN BULGARIAN WERE INVESTIGATED. CHROMATOGRAPHY AND HIGH-RESOLUTION INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY (HR-ICP-MS) WERE USED FOR EVALUATION OF PAHS, PCBS, MINERALS AND TRACE ELEMENTS. METHANOL EXTRACTS FROM RAPAPOL AND RAPANPOL (TO A LESSER DEGREE) CONTAINED RELATIVELY HIGH AMOUNTS OF FREE PHENOLICS (2.50 +/- 0.3 AND 1.57 +/- 0.18 MG GAE/G DW, RESPECTIVELY) AND EXHIBITED THE FOLLOWING RESPECTIVE LEVELS OF ANTIOXIDANT ACTIVITIES DETERMINED BY TWO RADICAL-SCAVENGING ASSAYS (MICROMTE/G DW): 1.8 +/- 0.2 AND 0.98 +/- 0.08 BY 1-DIPHENYL-2-PICRYLHYDRAZYL METHOD (DPPH); 1.74 +/- 0.17 AND 1.04 +/- 0.12 BY CUPRIC REDUCING ANTIOXIDANT CAPACITY (CUPRAC). THE TOTAL AMOUNTS OF ELEMENTS, PAHS AND PCBS WERE HIGHER IN RAPAPOL THAN IN RAPANPOL. THE OBTAINED INDICES OF RAPANA THOMASIANA CAN SERVE AS A BIOINDICATOR OF THE ENVIRONMENTAL ECOLOGICAL QUALITY.

THE VOLATILE FRACTIONS OF CAPE GOOSEBERRY AND BLUEBERRY WERE DETERMINED BY HEADSPACE SOLID-PHASE MICROEXTRACTION COUPLED WITH COMPREHENSIVE TWO-DIMENSIONAL GAS CHROMATOGRAPHY WITH TIME-OF-FLIGHT MASS SPECTROMETRY (HS-SPME/GC×GC-TOFMS). THE HIGHEST AMOUNT OF ALCOHOL (51.8%), ESTER (32.8%) AND CARBOXYLIC ACID (6.9%) WAS IN BLUEBERRY IN COMPARISON WITH GOOSEBERRY AND OPPOSITELY KETONES (14.7%), ALDEHYDES (9.9%) AND TERPENES (8%) WERE FOUND IN GOOSEBERRY. THE BIOACTIVE COMPOUNDS AND ANTIOXIDANT CAPACITIES WERE HIGHER IN BLUEBERRIES THAN IN GOOSEBERRIES. THREE DIMENSIONAL FLUORESCENCE EMISSION SPECTROMETRY (3D-FL) WAS APPLIED TO DETERMINE AND TO COMPARE EXPERIMENTALLY FOUND BINDING PARAMETERS OF BERRIES EXTRACTS WITH HUMAN SERUM ALBUMIN (HSA). THE FLUORESCENCE QUENCHING OF HSA BY POLYPHENOLS FROM BERRIES WAS A RESULT OF THE FORMATION OF A POLYPHENOL?HSA COMPLEX. THE BINDING ABILITIES OF BERRIES WERE HIGHLY CORRELATED WITH THE BIOACTIVITY OF POLYPHENOLS AND VOLATILE SUBSTANCES. THE CLUSTER ANALYSIS (CA) AND LINEAR DISCRIMINANT ANALYSIS (LDA) WAS APPLIED TO DIFFERENTIATE THE BERRIES SAMPLES ACCORDING TO THEIR TYPE.

THE EXPOSOME IS THE CUMULATIVE MEASURE OF ENVIRONMENTAL INFLUENCES AND ASSOCIATED BIOLOGICAL RESPONSES THROUGHOUT THE LIFESPAN, INCLUDING THOSE FROM THE ENVIRONMENT, DIET, BEHAVIOUR, AND ENDOGENOUS PROCESSES. THE EXPOSOME CONCEPT AND THE 2030 AGENDA FOR THE SUSTAINABLE DEVELOPMENT GOALS (SDGS) FROM THE UNITED NATIONS ARE THE BASIS FOR UNDERSTANDING THE AETIOLOGY AND CONSEQUENCES OF NON-COMMUNICABLE DISEASES, INCLUDING GESTATIONAL DIABETES MELLITUS (GDM). PREGNANCY MAY BE DEVELOPED IN AN ENVIRONMENT WITH ADVERSE FACTORS PART OF THE IMMEDIATE INTERNAL MEDIUM FOR FETUS DEVELOPMENT AND THE EXTERNAL MEDIUM TO WHICH THE PREGNANT WOMAN IS EXPOSED. THE PLACENTA IS THE INTERFACE BETWEEN MATERNAL AND FETAL COMPARTMENTS AND ACTS AS A PROTECTIVE BARRIER OR EASING AGENT TO TRANSFER EXPOSOME FROM MOTHER TO FETUS. UNDER AND OVER-NUTRITION IN UTERO, EXPOSURE TO ADVERSE ENVIRONMENTAL POLLUTANTS SUCH AS HEAVY METALS, ENDOCRINE-DISRUPTING CHEMICALS, PESTICIDES, DRUGS, PHARMACEUTICALS, LIFESTYLE, AIR POLLUTANTS, AND TOBACCO SMOKE PLAYS A DETERMINANT ROLE IN THE DEVELOPMENT OF GDM. THIS PHENOMENON IS WORSENED BY METABOLIC STRESS POSTNATALLY, SUCH AS OBESITY WHICH INCREASES THE RISK OF GDM AND OTHER DISEASES. CLINICAL RISK FACTORS FOR GDM DEVELOPMENT INCLUDE ITS AETIOLOGY. IT IS PROPOSED THAT KNOWLEDGE-BASED INTERVENTIONS TO CHANGE THE POTENTIAL INTERDEPENDENT ECTO-EXPOSOME AND ENDO-EXPOSOME COULD AVOID THE OCCURRENCE AND CONSEQUENCES OF GDM.

THE AIM OF THIS INVESTIGATION WAS TO INTRODUCE SEVERAL ANALYTICAL METHODS FOR DETERMINATION OF POLYCYCLIC AROMATIC HYDROCARBONS (PAHS), POLYCHLORINATED BIPHENYLS (PCBS), MINERALS, TRACE ELEMENTS, AND FATTY ACIDS IN RAPANA THOMASIANA AS A MARINE POLLUTION INDICATOR ORGANISM. THE CHEMICAL DIFFERENCES OF THE GASTROPOD RA. THOMASIANA FROM POLLUTED AND NONPOLLUTED SITES OF THE BLACK SEA ON THE BULGARIAN COAST WERE INVESTIGATED. CHROMATOGRAPHY AND HIGH-RESOLUTION INDUCTIVELY COUPLED PLASMA/MS ANALYSES WERE USED FOR EVALUATION OF PAHS, PCBS, FATTY ACIDS, MINERALS, AND TRACE ELEMENTS. THESE METHODS CAN BE APPLIED TO OTHER MARINE PRODUCTS.

THE OVERWHELMING RATES OF OBESITY WORLDWIDE ARE A MAJOR CONCERN DUE TO THE ELEVATED MEDICAL COSTS ASSOCIATED AND THE POOR QUALITY OF LIFE OF OBESE PATIENTS. IN THE RECENT YEARS, IT HAS BECOME EVIDENT THAT THE INTRAUTERINE MILIEU CAN HAVE A LONG-TERM IMPACT ON THE FOETUS HEALTH. THE PLACENTA IS A HIGHLY DYNAMIC ORGAN; WHOSE PRIMARY FUNCTION IS TO CARRY NUTRIENTS FROM THE MOTHER TO THE FOETUS AND TO REMOVE WASTE PRODUCTS FROM THE FOETUS. ANY ALTERATION IN MATERNAL CIRCULATING METABOLITES ELICITS A RESPONSE IN ORDER TO ENSURE THE DEVELOPING FOETUS AN ADEQUATE GROWTH ENVIRONMENT. THIS RESPONSE CAN BE TRANSLATED INTO EPIGENETIC MODIFICATIONS IN CODING GENES FOR METABOLIC-RELATED RECEPTORS LOCATED IN THE PLACENTA AND FOETAL TISSUES. THE MOST STUDIED RECEPTORS INVOLVED IN THE METABOLIC SENSING ARE THE LEPTIN AND THE INSULIN RECEPTORS. A MATERNAL METABOLIC DISEASE-LIKE STATE CAN ALTER THE EXPRESSION OF THESE RECEPTORS IN DIFFERENT ORGANS, INCLUDING PLACENTA. THERE IS EVIDENCE THAT THESE ALTERATIONS NOT ONLY AFFECT THE EXPRESSION LEVEL OF THESE RECEPTORS, BUT THERE ARE ALSO DIFFERENCES IN EPIGENETIC MARKS IN REGULATORY ELEMENTS OF THESE GENES THAT MAY BECOME PERMANENT DESPITE THE MOTHER S TREATMENT. THIS REVIEW PROVIDES EVIDENCE ABOUT POSSIBLE MECHANISMS INVOLVED IN THE FOETAL PROGRAMMING OF METABOLIC DISEASES ORIGINATED FROM THE PRE-NATAL ENVIRONMENT THAT COULD CONTRIBUTIVE TO INCREASING LEVELS OF OBESITY IN THE WORLD.

LAKE LAGUNA SANTA ELENA, A FRESHWATER BODY, LOCATED IN MID-SOUTH OF CHILE, IS AN ENVIRONMENTAL ASSET USED AS A WATER RESOURCE BY THE AGRICULTURAL AND TOURISTIC SECTOR AND IS THE HABITAT FOR A WIDE VARIETY OF ENDEMIC AVIFAUNA. THE OBJECTIVE OF THIS STUDY WAS TO ASSIGN A MONETARY VALUE TO THIS LACUSTRINE BODY, USING THE METHODOLOGY OF AMUVAM (MULTICRITERIA ANALYSIS OF ENVIRONMENTAL ACTIVE VALUES). THE INFORMATION WAS COLLECTED THROUGH THE APPLICATION OF SURVEYS TO A PANEL OF EXPERTS INVOLVED IN THE USE OF THE ENVIRONMENTAL RESOURCE. THE RESULT OBTAINED WITH THE AMUVAM METHOD CORRESPONDS TO THE US $ 17,780,686, A FIGURE THAT REPRESENTS AN ESTIMATED VALUE OF THE TEV (TOTAL ECONOMIC VALUE) OF THE ENVIRONMENTAL ASSET. THIS STUDY, A PIONEER IN THE REGION, WILL SUPPORT DECISION MAKING, ALLOWING AN ADEQUATE MANAGEMENT OF THIS CRITICAL WATER RESOURCE.

DIABESITY IS AN ABNORMAL METABOLIC CONDITION SHOWN BY PATIENTS WITH OBESITY THAT DEVELOP TYPE 2 DIABETES MELLITUS. PATIENTS WITH DIABESITY PRESENT WITH INSULIN RESISTANCE, REDUCED VASCULAR RESPONSE TO INSULIN, AND VASCULAR ENDOTHELIAL DYSFUNCTION. ALONG WITH THE SEVERAL WELL-DESCRIBED MECHANISMS OF INSULIN RESISTANCE, A STATE OF ENDOPLASMIC RETICULUM (ER) STRESS, WHERE THE PRIMARY HUMAN TARGETS ARE THE ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE FOETOPLACENTAL VASCULATURE, IS APPARENT. ER STRESS CHARACTERISES BY THE ACTIVATION OF THE UNFOLDED PROTEIN RESPONSE VIA THREE CANONICAL ER STRESS SENSORS, I.E., THE PROTEIN KINASE RNA-LIKE ENDOPLASMIC RETICULUM KINASE (PERK), INOSITOL-REQUIRING ENZYME 1? (IRE1?), AND ACTIVATING TRANSCRIPTION FACTOR 6. SLIGHTLY DIFFERENT CELL SIGNALLING MECHANISMS PREFERENTIALLY ENABLE IN DIABESITY IN THE ER STRESS-ASSOCIATED INSULIN RESISTANCE FOR ADIPOSE TISSUE (IRE1?/X-BOX BINDING PROTEIN 1 MRNA SPLICING/C-JUN N-TERMINAL KINASE 1 ACTIVATION), SKELETAL MUSCLE (TRIBBLES-LIKE PROTEIN 3 (TRB3)/PROINFLAMMATORY CYTOKINES ACTIVATION), AND LIVER (PERK/ACTIVATING TRANSCRIPTION FACTOR 4/TRB3 ACTIVATION). THERE IS NO INFORMATION IN HUMAN SUBJECTS WITH DIABESITY IN THE FOETOPLACENTAL VASCULATURE. HOWEVER, THE AVAILABLE LITERATURE SHOWS THAT PREGNANT WOMEN WITH PRE-PREGNANCY OBESITY OR OVERWEIGHT THAT DEVELOP GESTATIONAL DIABETES MELLITUS (GDM) AND THEIR NEWBORN SHOW INSULIN RESISTANCE. ER STRESS IS RECENTLY REPORTED TO BE TRIGGERED IN ENDOTHELIAL CELLS FROM THE HUMAN UMBILICAL VEIN FROM MOTHERS WITH PRE-PREGNANCY OBESITY. HOWEVER, WHETHER A DIFFERENT METABOLIC ALTERATION TO OBESITY IN PREGNANCY OR GDM IS PRESENT IN WOMEN WITH PRE-PREGNANCY OBESITY THAT DEVELOP GDM, IS UNKNOWN. IN THIS REVIEW, WE SUMMARISED THE FINDINGS ON DIABESITY-ASSOCIATED MECHANISMS OF INSULIN RESISTANCE WITH EMPHASIS IN THE PRIMARY TARGETS ADIPOSE, SKELETAL MUSCLE, LIVER, AND FOETOPLACENTAL TISSUES. WE ALSO GIVE EVIDENCE ON THE POSSIBILITY OF A NEW GDM-ASSOCIATED METABOLIC CO

THE ENTEROTOXIGENIC ESCHERICHIA COLI STRAINS LEAD TO DIARRHOEA IN HUMANS DUE TO HEAT-LABILE AND HEAT-STABLE (STA) ENTEROTOXINS. STA INCREASES CL-RELEASE IN INTESTINAL CELLS, INCLUDING THE HUMAN COLONIC CARCINOMA T84 CELL LINE, INVOLVING INCREASED CGMP AND MEMBRANE ALKALIZATION DUE TO REDUCED NA+/H+ EXCHANGERS (NHES) ACTIVITY. SINCE NHES MODULATE INTRACELLULAR PH (PHI), AND NHE1, NHE2, AND NHE4 ARE EXPRESSED IN T84 CELLS, WE CHARACTERIZED THE STA ROLE AS MODULATOR OF THESE EXCHANGERS. PHI WAS ASSAYED BY THE NH4CL PULSE TECHNIQUE AND MEASURED BY FLUORESCENCE MICROSCOPY IN BCECF-PRELOADED CELLS. PHI RECOVERY RATE (DPHI/DT) WAS DETERMINED IN THE ABSENCE OR PRESENCE OF 0.25 ?MOL/L STA (30 MINUTES), 25 ?MOL/L HOE-694 (CONCENTRATION INHIBITING NHE1 AND NHE2), 500 ?MOL/L SODIUM NITROPRUSSIDE (SNP, SPONTANEOUS NITRIC OXIDE DONOR), 100 ?MOL/L DIBUTYRYL CYCLIC GMP (DB-CGMP), 100 NMOL/L H89 (PROTEIN KINASE A INHIBITOR), OR 10 ?MOL/L FORSKOLIN (ADENYLYL CYCLASE ACTIVATOR). CGMP AND CAMP WERE MEASURED IN CELL EXTRACTS BY RADIOIMMUNOASSAY, AND BUFFERING CAPACITY (ßI) AND H+ EFFLUX (JH+) WAS DETERMINED. NHE4 PROTEIN ABUNDANCE WAS DETERMINED BY WESTERN BLOTTING. STA AND HOE-694 CAUSED COMPARABLE REDUCTION IN DPHI/DT AND JH+ (~63%), WITHOUT ALTERING BASAL PHI (RANGE 7.144-7.172). STA DID NOT ALTER ßI VALUE IN A RANGE OF 1.6 PHI UNITS. THE DPHI/DT AND JH+ WAS ALMOST ABOLISHED (~94% INHIBITION) BY STA + HOE-694. STA EFFECT WAS UNALTERED BY DB-CGMP OR SNP. HOWEVER, STA AND FORSKOLIN INCREASED CAMP LEVEL. STA-DECREASED DPHI/DT AND JH+ WAS MIMICKED BY FORSKOLIN, AND STA + HOE-694 EFFECT WAS ABOLISHED BY H89. THUS, INCUBATION OF T84 CELLS WITH STA RESULTS IN REDUCED NHE4 ACTIVITY LEADING TO A LOWER CAPACITY OF PHI RECOVERY REQUIRING CAMP, BUT NOT CGMP. STA EFFECT RESULTS IN A CAUSAL PHENOMENON (STA/INCREASED CAMP/INCREASED PKA ACTIVITY/REDUCED NHE4 ACTIVITY) ENDING WITH INTRACELLULAR ACIDIFICATION THAT COULD HAVE CONSEQUENCES IN THE GASTROINTESTINAL CELLS FUNCTION PROMOTING HUMAN DIARRHOEA

KIWI FRUITS ?HAYWARD? WERE SUBMITTED TO ETHYLENE TREATMENT DURING 24 H, FOLLOWING BY STORAGE AT 20C FOR 10 DAYS. SIGNIFICANT DIFFERENCES WERE FOUND IN POLYPHENOLS AND IN THE ANTIOXIDANT CAPACITIES IN CONVENTIONAL, LOW CHEMICAL AND ORGANIC KIWI FRUITS. ETHYLENE TREATMENT INCREASED THE BIOACTIVITY OF ORGANIC, LOW CHEMICAL AND CONVENTIONAL KIWI FRUIT. THE ANTIOXIDANT VALUES FOR ORGANIC FRUITS WERE SIGNIFICANTLY HIGHER THAN FOR CONVENTIONAL AND NONTREATED SAMPLES. ALL INVESTIGATED KIWI FRUITS SHOWED A HIGH LEVEL OF CORRELATION BETWEEN THE CONTENTS OF PHENOLIC COMPOUNDS, THEIR ANTIOXIDANT AND BINDING VALUES. THE STATISTICAL EVALUATION OF BIOACTIVITY DEMONSTRATED THAT CULTIVATION SYSTEM AND ETHYLENE TREATMENT FOLLOWING BY STORAGE HAVE THE POTENTIAL TO ENHANCE THE ACCUMULATION OF HEALTH-BENEFICIAL FOOD COMPOUNDS IN KIWI FRUIT AND CHANGES OF THE BINDING PROPERTIES.