Freshwater jellyfish in northeastern Argentina: a risk to human health.

BACKGROUND: Although cnidarians are mostly marine organisms, the occurrence of freshwater jellyfish frequently arouses the interest of ecologists, due to their sudden and unusual appearances in natural and artificial water bodies around the world. METHODS: This study describes a series of cases compatible with cnidarian envenomation that occurred coincidentally in time and space with the presence of Craspedacusta sowerbii Lankester, 1880 jellyfish in the province of Misiones (El Saltito stream) in January 2022. A year later, its presence was confirmed in another watercourse of this province (Cazador stream). Based on these findings, its possible toxicological consequences in humans were evaluated by characterizing the jellyfish extract using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and enzymatic/toxic activities. RESULTS: We revealed the presence of proteolytic enzymes and cytolytic toxin(s), which-by means of activating the inflammatory cascade-could explain the stinging skin lesions observed in the suspected cases described. CONCLUSIONS: In addition to recording for the first time the occurrence of this cnidarian in northeastern Argentina, this work provides, for the first time, a toxinological explanation for the clinical observations after contact with the most widespread freshwater jellyfish species in the world, giving support to health professionals in the diagnosis and management of such accidents/envenomation.

Síndrome inflamatorio multisistémico asociado a COVID-19 en pediatría: serie de casos en servicios públicos de salud de Neuquén / Multisystem inflammatory syndrome associated with COVID-19 in children: case series in Neuquén public health services

INTRODUCCIÓN: Durante la pandemia por SARS-CoV-2 se reportaron casos de un síndrome de inflamación multisistémica similar a la enfermedad de Kawasaki con antecedente de infección reciente o contacto con casos de COVID-19, generando una relación temporal con dicha enfermedad (SIM-C). El objetivo de este trabajo fue caracterizar los aspectos clínicos y epidemiológicos de los casos de SIM-C en menores de 18 años. MÉTODOS: Se realizó un estudio transversal, observacional y descriptivo de casos de SIM-C en menores de 18 años asistidos entre marzo de 2020 y junio de 2022 en el sistema público de la provincia de Neuquén. RESULTADOS: Serie de casos: Se incluyó a 9 pacientes con SIM-C: 55,5% de sexo femenino, con una media de edad de 6,1 años. El 77,7% de los casos de COVID-19 fueron confirmados por nexo epidemiológico. Todos los pacientes presentaron fiebre previa a la internación, el 88,8% tuvo manifestaciones mucocutáneas y compromiso abdominal. Otras manifestaciones frecuentes fueron compromiso ocular y edema de manos. El 33,3% de los pacientes requirieron internación en unidades de cuidados intensivos pediátricos. Solo 1 necesitó asistencia respiratoria mecánica por 48 horas por shock. Todos los pacientes fueron tratados con inmunoglobulina intravenosa (IGIV) 2 g/kg, y 3 pacientes recibieron corticoterapia. No hubo fallecimientos ni complicaciones en el seguimiento. DISCUSIÓN: Aunque el pronóstico es favorable, se sugiere realizar estudios que monitoreen los efectos a largo plazo de SIM-C.

Clinical Efficacy of SARS-CoV-2 Vaccination in Hemodialysis Patients.

Introduction: The COVID-19 pandemic is a global public health problem. Patients with end-stage renal disease on hemodialysis are at a higher risk of infection and mortality than the general population. Worldwide, a vaccination campaign has been developed that has been shown to reduce severe infections and deaths in the general population. However, there are currently limited data on the clinical efficacy of vaccinations in the hemodialysis population. Methods: A national multicenter observational cohort was performed in Chile to evaluate the clinical efficacy of anti-SARS-CoV-2 vaccination in end-stage renal disease patients on chronic hemodialysis from February 2021 to August 2021. In addition, the BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines were evaluated. The efficacy of vaccination in preventing SARS-CoV-2 infection, hospitalizations, and deaths associated with COVID-19 was determined. Results: A total of 12,301 patients were evaluated; 10,615 (86.3%) received a complete vaccination (2 doses), 490 (4.0%) received incomplete vaccination, and 1196 (9.7%) were not vaccinated. During follow-up, 1362 (11.0%) patients developed COVID-19, and 150 died (case fatality rate: 11.0%). The efficacy of the complete vaccination in preventing infection was 18.1% (95% confidence interval [CI]:11.8-23.8%), and prevention of death was 66.0% (95% CI:60.6-70.7%). When comparing both vaccines, BNT162b2 and CoronaVac were effective in reducing infection and deaths associated with COVID-19. Nevertheless, the BNT162b2 vaccine had higher efficacy in preventing infection (42.6% vs. 15.0%) and deaths (90.4% vs. 64.8%) compared to CoronaVac. Conclusion: The results of our study suggest that vaccination against SARS-CoV-2 in patients on chronic hemodialysis was effective in preventing infection and death associated with COVID-19.

Rethinking the term "glyphosate effect" through the evaluation of different glyphosate-based herbicide effects over aquatic microbial communities.

Glyphosate-based herbicides (GBH) -the most widely used herbicides in agriculture worldwide-are frequently generalized by the name of "glyphosate". However, GBH encompass a variety of glyphosate salts as active ingredient and different adjuvants, which differ between products. These herbicides reach water bodies and produce diverse impacts over aquatic communities. Yet, the risk assessment assays required for the approval focus mostly on active ingredients. Herein, we compared the effect of five different GBH as well as of monoisopropylamine salt of glyphosate (GIPA) on aquatic microbial communities from natural shallow lakes that were mixed and allowed to evolve in an outdoor pond. We performed an 8-day long assay under indoor control conditions to evaluate the effects of exposure on the structure of nano-plus microphytoplankton (net phytoplankton, with sizes between 2 and 20 µm and >20 µm, respectively) and picoplankton (size ranging between 0.2 and 2 µm) communities through microscopy and flow cytometry, respectively. Significantly different effects were evident on the structure of microbial communities dependent on the GBH, even with herbicides sharing similar active ingredients. Each GBH evoked increases of different magnitude in bacterioplankton abundance. Furthermore, GIPA and a formulation decreased the abundance of a phycocyanin-rich (PC-rich) picocyanobacteria (Pcy) cytometric population and GIPA further altered Pcy composition. Also, two GBH increased net phytoplankton total abundance and, unlike the tested GBH, no apparent effect of GIPA was detected on this community structure. These results demonstrate that GBH effects on aquatic microbial communities should not be summarized as "glyphosate" effects considering that the formulations have effects beyond those exerted by the active ingredients alone. This work intends to alert on the lack of real knowledge regarding the consequences of the variety of GBH on natural aquatic ecosystems. Indeed, the wide use of the term "glyphosate effect" should be thoroughly rethought.

An invasive mussel is in trouble: How do glyphosate, 2,4-D and its mixture affect Limnoperna fortunei's survival?

Contamination and biological invasions are important factors that alter the functioning of freshwater systems. We carried out two experiments involving daily measurements of dissolved oxygen (DO) and Limnoperna fortunei mortality: 1) the impact of DO on mussel survival mediated by glyphosate, 2,4-D and their mixture was analysed in a 22-day indoor experiment (IE) under controlled conditions using microcosms with L. fortunei, with and without air supply; and 2) the effect of each herbicide and their mixture on mussel accumulated mortality was compared in a 18-day outdoor experiment (OE) using mesocosms without air supply, with and without L. fortunei. Results showed that glyphosate, alone or mixed affected L. fortunei survival both directly and indirectly. In IE we observed direct toxicity of glyphosate in treatments with air supply, with accumulated mortality of 20.0% for glyphosate and 10.0% for the mixture. In OE, L. fortunei deepened the changes in the patterns of DO fluctuations driven by the herbicides, which led to hypoxia in the system. The accumulated mortality was 46.7, 8.6 and 48.2% for glyphosate, 2,4-D and the mixture, respectively. This study contributes to the understanding of the mechanisms that control the invasion of L. fortunei in freshwater systems influenced by agrochemicals.

64Cu PET Imaging of the CXCR4 Chemokine Receptor Using a Cross-Bridged Cyclam Bis-Tetraazamacrocyclic Antagonist.

Expression of the chemokine receptor chemokine C-X-C motif receptor 4 (CXCR4) plays an important role in cancer metastasis, in autoimmune diseases, and during stem cell-based repair processes after stroke and myocardial infarction. Previously reported PET imaging agents targeting CXCR4 suffer from either high nonspecific uptake or bind only to the human form of the receptor. The objective of this study was to develop a high-stability 64Cu-labeled small-molecule PET agent for imaging both human and murine CXCR4 chemokine receptors. Methods: Synthesis, radiochemistry, stability and radioligand binding assays were performed for the novel tracer 64Cu-CuCB-bicyclam. In vivo dynamic PET studies were performed on mice bearing U87 (CXCR4 low-expressing) and U87.CXCR4 (human-CXCR4 high-expressing) tumors. Biodistribution and receptor blocking studies were performed on CD1-IGS immunocompetent mice. CXCR4 expression on tumor and liver disaggregates was confirmed using a combination of immunohistochemistry, quantitative polymerase chain reaction, and Western blot. Results:64Cu-CuCB-bicyclam has a high affinity for both the human and the murine variants of the CXCR4 receptor (half-maximal inhibitory concentration, 8 nM [human]/2 nM [murine]) and can be obtained from the parent chelator that has low affinity. In vitro and in vivo studies demonstrate specific uptake in CXCR4-expressing cells that can be blocked by more than 90% using a higher-affinity antagonist, with limited uptake in non-CXCR4-expressing organs and high in vivo stability. The tracer was also able to selectively displace the CXCR4 antagonists AMD3100 and AMD3465 from the liver. Conclusion: The tetraazamacrocyclic small molecule 64Cu-CuCB-bicyclam has been shown to be an imaging agent for the CXCR4 receptor that is likely to be applicable across a range of species. It has high affinity and stability and is suitable for preclinical research in immunocompetent murine models.

Synthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression.

BACKGROUND: The histological evaluation of estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer lesions from biopsy tissue can stratify patients to receive endocrine therapy. Furthermore, PR expression can predict response to selective estrogen receptor modulators (SERMs). Current immunohistochemical approaches to PR detection are limited by sampling error associated with biopsy and lack of standardised protocols; positron emission tomography (PET) using receptor targeted radiopharmaceuticals to provide quantitative, whole-body imaging may overcome these limitations. PR expression has been successfully imaged with PET in the clinical setting, however investigation into new radioligands with improved pharmacokinetics and metabolic stability is desirable. RESULTS: We report the synthesis of a focused library of non-steroidal PR ligands evaluated for use as PET radioligands. A lead candidate ([18F]2) with low nanomolar activity was selected and radiolabelled with a radiochemical yield of 2.29 ± 2.31% (decay-corrected), radiochemical purity (RCP) > 95% and a molar activity of 2.5 ± 1.6 GBq/µmol. Cell uptake studies showed a significant and specific accumulation of [18F]2 in T47D (PR++) breast cancer cell compared to MDA-MB-231 (PR-) control; however, in vivo evaluation was confounded by rapid defluorination of the radioligand. In vitro metabolite analysis of 2 in MLM confirmed defluorination and oxidative metabolism of the thiocarbamate to oxocarbamate moiety by mass spectrometry. CONCLUSIONS: A route to access [18F]2 was developed to allow in vitro and in vivo evaluation, albeit with low radiochemical yield and modest molar activity. [18F]2 demonstrated selective uptake in PR++ T47D cells which could be blocked in a dose dependent manner with progesterone. However, [18F]2 showed poor in vivo metabolic stability with rapid defluorination within the time frame of the imaging protocol.

FACTOR DE CRECIMIENTO ENDOTELIAL TIPO A EN PACIENTES ADULTOS CON DERMATITIS ATÓPICA

Estudiamos la influencia del factor de crecimiento endotelial tipo A en pacientes con dermatitis atópica, que es una enfermedad inflamatoria, crónica, recidivante de la piel, que altera la calidad de vida. Se ha visto que el VEGF A podría estar relacionado con la fisiopatología de esta enfermedad. Otro de los objetivos fue determinar el nivel plasmático de Ig E en pacientes enfermos y sanos. Es un estudio clínico, observacional, transversal y analítico en el cual se determinó el valor de VEGF A en suero en 10 paciente con diagnóstico de DA y 10 paciente correspondiente al grupo control. Otras variables estudiadas fueron sexo, edad, antecedentes patológicos alérgicos, antecedentes familiares alérgicos, inicio de la enfermedad, sintomatología mucocutánea, síntomas sistémicos acompañante, valores de Ig E sérica total, pruebas de Prick test, pruebas de hipersensibilidad retardada Parches Cutáneos. Se analizó el VEGF-A sérico mediante inmunoensayo enzimático siguiendo las instrucciones del fabricante (Human VEGF-A Platinum) ELISA. Como conclusión en este trabajo se pudo observar que no hubo relación con el aumento de VEGF A sérico en pacientes con DA, probablemente porque se produzca en región local de la lesión inflamatoria. Se requiere un mayor estudio para su análisis.

We studied the influence of endothelial growth factor type A on patients with atopic dermatitis, which is an inflammatory, chronic, recurrent disease of the skin, which alters the quality of life. It has been shown that VEGF A may be related to the pathophysiology of this disease. Another objective was to determine the plasma level of IgE in sick and healthy patients. It is a clinical, observational, transversal and analytical study in which the value of VEGF A in serum was determined in 10 patients with diagnosis of AD and 10 patients corresponding to the control group. Other variables were sex, age, allergic pathological history, allergic family history, onset of disease, mucocutaneous symptomatology, accompanying systemic symptom, total serum IgE values, Prick test, delayed hypersensitivity tests Skin Patches. Serum VEGF- A was analyzed by enzyme immunoassay following the manufacturer's instructions (Human VEGF-A Platinum) ELISA. As conclusion, in this work it was observed that there was no relationship with the increase of serum VEGF A in patients with AD probably because it occurs in the local region of the inflammatory lesion. Further study is required for analysis.

Structure of the monofunctional heme catalase DR1998 from Deinococcus radiodurans.

UNLABELLED: Deinococcus radiodurans is an aerobic organism with the ability to survive under conditions of high radiation doses or desiccation. As part of its protection system against oxidative stress, this bacterium encodes three monofunctional catalases. The DR1998 catalase belongs to clade 1, and is present at high levels under normal growth conditions. The crystals of DR1998 diffracted very weakly, and the merged diffraction data showed an R sym of 0.308. Its crystal structure was determined and refined to 2.6 Å. The four molecules present in the asymmetric unit form, by crystallographic symmetry, two homotetramers with 222 point-group symmetry. The overall structure of DR1998 is similar to that of other monofunctional catalases, showing higher structural homology with the catalase structures of clade 1. Each monomer shows the typical catalase fold, and contains one heme b in the active site. The heme is coordinated by the proximal ligand Tyr369, and on the heme distal side the essential His81 and Asn159 are hydrogen-bonded to a water molecule. A 25-Å-long channel is the main channel connecting the active site to the external surface. This channel starts with a hydrophobic region from the catalytic heme site, which is followed by a hydrophilic region that begins on Asp139 and expands up to the protein surface. Apart from this channel, an alternative channel, also near the heme active site, is presented and discussed. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank in Europe under accession code 4CAB.

Purification, crystallization and phase determination of the DR1998 haem b catalase from Deinococcus radiodurans.

The protective mechanisms of Deinococcus radiodurans against primary reactive oxygen species involve nonenzymatic scavengers and a powerful enzymatic antioxidant system including catalases, peroxidases and superoxide dismutases that prevents oxidative damage. Catalase is an enzyme that is responsible for the conversion of H2O2 to O2 and H2O, protecting the organism from the oxidative effect of H2O2. This study reports the purification and crystallization of the DR1998 catalase from D. radiodurans. The crystals diffracted to 2.6 Å resolution and belonged to space group C2221, with unit-cell parameters a = 97.33, b = 311.88, c = 145.63 Å, suggesting that they contain four molecules per asymmetric unit. The initial phases were determined by molecular replacement and the obtained solution shows the typical catalase quaternary structure. A preliminary model of the protein structure has been built and refinement is currently in progress.

Características clínicas y epidemiológicas de la epidemia de dengue en el municipio de Santiago de Cuba / Clinical and epidemiological characteristics of dengue epidemic in Santiago de Cuba municipality

Se realizó un estudio descriptivo y transversal de 13 147 pacientes del municipio Santiago de Cuba, a fin de caracterizar desde el punto de vista clinicoepidemiológico la epidemia de dengue que afectó a dicho municipio desde 2006 hasta 2007, para lo cual se constituyó un equipo multidisciplinario formado por epidemiólogos, clínicos, pediatras y ginecoobstetras. Se caracterizaron los casos según variables de interés clinicoepidemiológico. Predominaron el sexo femenino (50,6 %) en los mayores de 15 años (92,3 %), la forma clínica de dengue clásico (98,6 %) y julio-agosto-septiembre como los meses de mayor notificación de casos. Se conoció la morbimortalidad en una población susceptible a un nuevo serotipo no identificado anteriormente y se demostró que la infección secundaria en menores no fue suficiente para producir las formas hemorrágicas de esta enfermedad; por tanto, se recomendó mantener estrecha vigilancia sobre los viajeros procedentes de áreas endémicas y con altos índices vectoriales.

A descriptive and cross-sectional study of 13 147 patients from Santiago de Cuba municipality was carried out, in order to characterize the dengue epidemic from the clinical and epidemiological point of view, which affected this municipality from 2006 to 2007, for this purpose a multidisciplinary team was formed by epidemiologists, clinical doctors, pediatricians and gyneco-obstetricians. Cases were characterized according to variables of clinical and epidemiological interest. Female sex (50.6%) in those under 15 years (92.3%), the clinical classical form of dengue (98.6%) and July-August-September as the months of higher notification of cases. Morbimortality was known in a population susceptible to a previously non identified new serotype and it was shown that the secondary infection in the younger population was not enough to produce the hemorrhagic forms of this disease; therefore, it was recommended to maintain close control on the travellers coming from endemic areas and with high vectorial indexes.

Brotes de transmisión de dengue en asentamientos poblacionales de Santiago de Cuba / Outbreaks of dengue transmission in population settlements from Santiago de Cuba

Se realizó un estudio no explicativo, descriptivo y transversal para caracterizar los brotes de dengue en asentamientos poblacionales del municipio de Santiago de Cuba durante el 2010. El universo estuvo constituido por 2 084 personas y 1 410 viviendas y locales. La información se obtuvo de la base de confirmados y de focos de Aedes aegypti, de las historias epidemiológicas y de los informes de la Unidad Municipal de Higiene y Epidemiología. En la serie, 4 localidades se encontraban entre 7½ y 39 km de la ciudad, 5 presentaban patrones de urbanización inadecuados (80,2 %), la tasa de incidencia fue de 42,2 por 1000 habitantes, con primacía en el sexo femenino y predominaron las edades de 18- 49 años (69,8 %). Fueron identificados riesgos ambientales y 126 focos de Aedes aegypti, con mayores índices en Begoña y Sigua; también se detectaron 156 depósitos positivos en tanques bajos y artificiales (56,4 y 26,3 %, respectivamente).

A non-explanatory, descriptive and cross-sectional study to characterize the dengue outbreaks in population settlements of Santiago de Cuba municipality was carried out during the 2010. The universe was formed by 2 084 persons and 1 410 houses and locals. The information was obtained from the register of confirmed cases and of Aedes aegypti foci, of the epidemiological records and of reports from the Municipal Hygiene and Epidemiology Unit. In the series, 4 towns were between 7½ and 39 km from the city, 5 had inadequate urbanization patterns (80.2 %), the incidence rate was 42.2 per 1000 inhabitants, with primacy in the female sex and ages from18 to 49 years (69.8 %) prevailed. Environmental risks and 126 foci of Aedes aegypti were identified, with higher figures in Begoña and Sigua; 156 positive deposits were also detected in low and artificial deposits (56.4 and 26.3%, respectively).

Relación del polimorfismo C-514T del gen de la lipasa hepática con indicadores nutricionales y lipoproteínas en una muestra poblacional peruana: una perspectiva nutrigenética / Relation of the hepatic lipase gene C-514T polymorphism with nutritional indicators and lipoproteins in a peruvian population sample: a nutrigenetic perspective

Introducción: Las enfermedades cardiovasculares son una de las principales causas de muerte en todo el mundo. El promotor del gen de la lipasa hepática presenta un polimorfismo funcional C-514T que se relaciona con la actividad de la enzima, la variación de los niveles de lipoproteínas y un posible riesgo para desarrollar enfermedades cardiovasculares. Objetivos: Establecer la relación del polimorfismo C-514T del promotor del gen de la lipasa hepática con indicadores nutricionales y los niveles de lipoproteínas plasmáticas en una muestra de peruanos saludables. Diseño: Estudio descriptivo, transversal, asociativo. Lugar: Centro de Investigación de Bioquímica y Nutrición Alberto Guzmán Barrón, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Participantes: Noventiuna personas sanas de ambos sexos, cuyas edades fluctuaban entre 18 y 58 años, voluntarios con consentimiento informado. Intervenciones: Extracción del ADN genómico a partir de muestras sanguíneas según metodología estándar. Toma de medidas antropométricas, estableciéndose los indicadores nutricionales, determinación del perfil lipídico por el método enzimático. Análisis del polimorfismo C-514T mediante la técnica de PCR/RFLP, con primers específicos y digestión con la enzima de restricción NlaIII, detectándose los fragmentos de RFLP por electroforesis en gel de poliacrilamida (PAGE) y tinción con nitrato de plata. Principales medidas de resultados: Frecuencias genotípicas y alélicas del gende la lipasa hepática y relación con parámetros lipídicos y nutricionales. Resultados: Se encontró las frecuencias genotípicas CC=0,143; CT=0,593 y TT = 0,264, siendola distribución consistente con el equilibrio de Hardy-Weinberg (X2 =3,8024, g.l.=1, p = 0,086). Las frecuencias alélicas fueron alelo C = 0,4395 y el alelo T = 0,5605. Los niveles de colesterol, HDLc, LDLc, TG y los promedios de pliegue subcutáneo, el IMC y el porcentaje de grasa en los genotipos CC, CT y TT.

Introduction: Cardiovascular diseases are major causes de death in the world. The hepatic lipase (HL) gene promoter region presents a C-514T functional polymorphism related to enzyme activity, variation of lipoproteins levels and possible cardiovascular disease risk. Objectives: To determine the association of HL gene promoter region polymorphism with both nutritional indicators and lipoproteins levels in a healthy Peruvian sample. Design: Descriptive, transversal, associative study. Setting: Alberto Guzman Barron Biochemistry and Nutrition Research Center, Faculty of Medicine, Universidad Nacional Mayor de San Marcos. Participants: Ninety healthy male and female volunteers aged 18 to 58 years. Interventions: Genomic DNA was obtained from serum samples according to standard methodology. Anthropometric measurements and lipid profile byenzymatic methods were performed. Polymorphism C-514T in the HL gene was determined by polymerase chain reaction (PCR). PCR products were digested with NlaIII and fragments separated by polyacrilamyde gel electrophoresis (PAGE) and stained with silver nitrate. Main outcome measures: HL gene genotypes and alleles frequencies and relation with both lipid and nutritional parameters. Results: We found genotype frequencies CC=0,143; CT=0,593 and TT = 0,264, consistent with Hardy-Weinberg equilibrium (X2 =3,8024, g.l. = 1, p = 0,086). Alleles frequencies were C allele = 0,4395 and T allele = 0,5605. HDLc, LDLc, TAG cholesterol levels and subcutaneous fold, BMI and fat percentage averages in CC, CT and TT genotypes did not show significant differences (p > 0,05). Nevertheless, when T allele was analyzed alone (genotypes CT and TT) according to age and sex there were significant differences (p < 0,05) in some parameters.

Polimorfismo val108/158Met en el gen dopaminérgico catecol o-metil transferasa (COMT) en una población mixta peruana y su importancia para los estudios neuropsiquiátricos / Val108/158Met polymorphism in the catechol-o-methyl transferase (COMT) dopaminergic gene in mestizo Peruvian population and its importance in neuropsychiatric studies

Introducción: El gen dopaminérgico catecol-o-metil transferasa (COMT), tiene un polimorfismo funcional Val108/158Met que da lugar a variantes de la enzima que cataliza la o-metilación de las catecolaminas activas, participando en el metabolismo de las drogas y neurotransmisores, como la L-dopa, norepinefrina, epinefrina y dopamina y, por consiguiente, puede asociarse a condiciones neuropsiquiátricas. Objetivos: Determinar las frecuencias genotípicas y alélicas del polimorfismo Val108/158Met del gen COMT en sujetos saludables de una población mixta peruana y establecer las implicancias para el estudio genético de enfermedades y otras condiciones neuropsiquiátricas. Diseño: Estudio descriptivo, observacional, transversal. Lugar: Centro de Investigación de Bioquímica y Nutrición æAlberto Guzmán BarrónÆ. Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Participantes: Ciento seis personas, hombres y mujeres, clínicamente saludables, sin enfermedades neurológicas ni mentales u otra patología similar, voluntarios con consentimiento informado, sin relación de parentesco, todos residentes en Lima, cuyas edades fluctuaban entre los 18 y 50 años. Intervenciones: Extracción del ADN genómico a partir de células de epitelio bucal, según metodología estándar. Amplificación mediante la PCR con primers específicos y digestión con la enzima de restricción NlaIII. Detección de fragmentos de restricción de longitud polimórfica (RFLP) por electroforesis en gel de poliacrilamida al 6 por ciento, teñido con nitrato de plata. Principales medidas de resultados: Frecuencias genotípicas y alélicas del gen COMT en población mixta peruana. Resultados: Se encontró las frecuencias genotípicas Met/Met=0,0661, Val/Met=0,5094 y Val/Val=0,4245, siendo la distribución consistente con el equilibrio de Hardy-Weinberg (X2 =3,0317, g.l.=1, p mayor que 0,05). Las frecuencias alélicas encontradas fueron alelo Val=0,68 y el alelo Met=0,32. Conclusiones: El genotipo heterocigoto...

Introduction: Dopaminergic catechol-o-methyl transferase (COMT) gene has a functional polymorphism Val108/158Met that originates enzyme variants that catalyze o-methylation of active catecholamines and participates in drugs and neurotransmitters metabolism including L-dopa, norepinephrine, epinephrine and dopamine and thus may be associated to neuropsychiatric conditions. Objectives: To determine COMT gene genotypes and alleles frequencies in mestizo Peruvian population healthy subjects and its importance in neuropsychiatric genetic studies. Design: Descriptive, observational, transversal study. Setting: Alberto Guzman Barron Biochemistry and Nutrition Research Center, Faculty of Medicine, Universidad Nacional Mayor de San Marcos. Participants: One hundred and six healthy subjects, male and female volunteers with informed consent, without family relationship or mental and neurological disorders as determined by clinical assessment, all Lima residents, aged between 18 and 50 years. Interventions: Genomic DNA was extracted from buccal epithelium cells to 106 individuals seemingly healthy, previous informed consent, using standard methodology. We typed using polymerase chain reaction (PCR) of the relevant region followed by digestion with N1aIII enzyme and polyacrilamyde gel electrophoresis and silver nitrate stain. Main outcomes measures: COMT gene genotypes and alleles frequencies in mixed Peruvian population. Results: We found frequencies Met/Met genotype=0,0661, Val/Met genotype=0,5094, and Val/Val genotype=0,4245, distribution consistent with Hardy Weinberg expectations (X2 = 3,0317, g.l.=1, p major 0,05). Alleles frequencies were Val allele=0,679 and Met allele=0,321. Conclusions: Val/Met heterozygote and Val allele were significantly more common in the mixed Peruvian population. In gene-gene interaction and gene environment Val108/158Met polymorphism must be considered in neuropsychiatric genetic studies in both mixed and native populations.