A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients.

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

The effect of second-generation antidepressant treatment on the attention and mental processing speed of patients with major depressive disorder: A meta-analysis study with structural equation models.

Major depressive disorder (MDD) has been linked to attention and mental processing speed deficits that can be improved after pharmacological treatment. However, it is unclear whether a class of antidepressants is more effective than others to ameliorate these deficits in MDD. Additionally, the possible effects of clinical and demographic variables on improving MDD attention and processing speed deficits after antidepressant treatment are unknown. We aimed to study the possible neuropsychological effects of second-generation antidepressant classes on the attention and processing speed of MDD patients and the potential influences of clinical and demographic variables as moderators of these effects using a meta-analytic approach. Twenty-five papers were included in our study. A structural equation model meta-analysis was performed. The improvement of attention and processing speed after pharmacological treatment is clinically relevant but incomplete. Selective serotonin reuptake inhibitors (SSRIs) and dual inhibitors are the drugs causing the greatest improvement in the processing speed of MDD patients. Antidepressant class is an important variable linked to processing speed improvement after MDD treatment. However, the degree of improvement in both cognitive functions is strongly influenced by some clinical and demographic variables of depressed patients, such are age and education of the MDD patients, the duration of the antidepressant treatment, and the depression status of the patients.

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection. Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality. Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed. Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group. Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.

Análisis de la calidad de la anticoagulación con antagonistas de la vitamina K en tres escenarios clínicos en México / Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico

Resumen Introducción: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. Objetivo: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. Métodos: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. Resultados: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. Conclusiones: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Abstract Introduction: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. Objective: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. Methods: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. Results: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. Conclusions: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

Validation of the Role of Thrombin Generation Potential by a Fully Automated System in the Identification of Breast Cancer Patients at High Risk of Disease Recurrence.

Background The measurement of thrombin generation (TG) potential by the calibrated automated thrombogram (CAT) assay provides a strong contribution in identifying patients at high risk of early disease recurrence (E-DR). However, CAT assay still needs standardization and clinical validation. Objective In this study, we aimed to validate the role of TG for E-DR prediction by means of the fully automated ST Genesia system. Methods A prospective cohort of 522 patients from the HYPERCAN study with newly diagnosed resected high-risk breast cancer was included. Fifty-two healthy women acted as controls. Plasma samples were tested for protein C, free-protein S, and TG by ST Genesia by using the STG-ThromboScreen reagent with and without thrombomodulin (TM). Results In the absence of TM, patients showed significantly higher peak and ETP compared with controls. In the presence of TM, significantly lower inhibition of ETP and Peak were observed in patients compared with controls. E-DR occurred in 28 patients; these patients had significantly higher peak and endogenous thrombin potential (ETP) in the absence of TM compared with disease-free patients. Multivariable analysis identified mastectomy, luminal B HER2-neg, triple negative subtypes, and ETP as independent risk factors for E-DR. These variables were combined to generate a risk assessment score, able to stratify patients in three-risk categories. The E-DR rates were 0, 4.7, and 13.5% in the low-, intermediate-, and high-risk categories (hazard ratio = 8.7; p < 0.05, low vs. high risk). Conclusion Our data validate the ETP parameter with a fully automated standardized system and confirm its significant contribution in identifying high-risk early breast cancer at risk for E-DR during chemotherapy.

THE EFFECT OF SECOND-GENERATION ANTIDEPRESSANT TREATMENT ON THE EXECUTIVE FUNCTIONS OF PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A META-ANALYSIS STUDY WITH STRUCTURAL EQUATION MODELS.

Major depressive disorder (MDD) has been linked to executive functions (EF) deficits that can be improved after pharmacological treatment, but it is unclear whether there is a class of antidepressants that is more effective than others to ameliorate these deficits in MDD. Additionally, the possible effects of clinical and demographic variables on the improvement of MDD EF deficits after pharmacological treatment are currently unknown. Our aim was to study the possible neuropsychological effects of second-generation antidepressant classes on the EF of MDD patients and the potential influence of clinical and demographic variables as moderators of these effects through a meta-analytic approach. Twenty-one papers were included in our study. A structural equation model meta-analysis was performed. The improvement of EF after pharmacological treatment is clinically relevant, but it is incomplete. This effect is influenced by age and years of education of the patients. Selective serotonin reuptake inhibitors (SSRIs) and dual inhibitors are the drugs causing the greatest improvement in EF of MDD patients. Antidepressant class is an important variable linked to EF improvement after MDD treatment, but the degree of improvement in these cognitive functions is strongly influenced by some clinical and demographic variables of patients with depression.

Low levels of ADAMTS-13 with high anti-ADAMTS-13 antibodies during remission of immune-mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: A multi-institutional study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening immune-mediated thrombotic microangiopathy. Daily therapeutic plasma exchange (TPE) and the optimized use of rituximab have strikingly improved the outcome of this disease, however the rate of disease recurrence remains high. Specific predictors of relapse in patients in remission can be relevant for an optimal patient management. In this study, we aimed to identify predictive variables of disease relapse in a multicenter cohort of 74 out of 153 iTTP patients. They were tested at different time points during remission for the levels of ADAMTS-13 activity and autoantibody, and did not receive pre-emptive treatment for ADAMTS-13 activity deficiency during remission. The results showed that the association of ADAMTS13 activity ≤20% with a high anti-ADAMTS-13 titer at remission, and the time to response to first line treatment ≥13 days, were independent predictive factors of disease relapse. In addition, the use of rituximab in patients with exacerbation or refractoriness to TPE was significantly associated with reduced relapse rate. By Cox regression analysis, patients with ADAMTS-13 activity ≤20% plus anti-ADAMTS13 antibody titer ≥15 U/mL at remission had an increased risk of relapse (HR 1.98, CI 95% 1.087-3.614; P < .02). These findings may help to outline more personalized therapeutic strategies in order to provide faster and sustained responses to first-line iTTP treatment and prevent relapses in these patients.

The Effect of Second-Generation Antidepressant Treatment on the Memory of Patients With Major Depressive Disorder: A Meta-analysis Study With Structural Equation Models.

BACKGROUND: Major depressive disorder (MDD) has been linked to episodic memory deficits that may be improved after pharmacological treatment, but it is unclear whether there is a class of antidepressants that is more effective than others to ameliorate these deficits in MDD. In addition, the possible effects of clinical and sociodemographic variables on the improvement of MDD memory deficits after pharmacological treatment are currently unknown. Our aims are to study the possible neuropsychological effects of second-generation antidepressant classes on the episodic memory of MDD patients and to study the potential effects of clinical and demographic variables as moderators of the effects of antidepressants on the memory of depressed patients through a meta-analysis approach. PROCEDURES: Nine articles were included in our study. A structural equation model meta-analysis was performed. RESULTS: Our results suggest that selective serotonin reuptake inhibitors and serotonine-noradrenaline reuptake inhibitors would bring about a substantial improvement in the memory of depressed patients, whereas other antidepressant classes would cause rather modest effects. Our results also suggest that clinical and demographic variables play a very important role as mediators of memory improvement after MDD treatment. Thus, a relatively low level of symptom severity, a high degree of clinical improvement, a younger age, and more years of education were positively related to memory improvement after MDD treatment. CONCLUSIONS: Although antidepressant class is an important variable linked to memory improvement in MDD, overall, the degree of memory amelioration in depression is very closely related to clinical and demographic variables of patients with depression.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Endocrine disruptor effect of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on porcine ovarian cell steroidogenesis.

Previous studies with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) indicate that they act as endocrine disruptors, in addition to inducing alterations and damaging reproductive health; however, the biological mechanisms by which these disorders are produced are not yet understood. The aim of this study was to analyze the effect of PFOS and PFOA on in vitro steroidogenic secretion in porcine theca and granulosa cells, with or without gonadotropic stimulation. Granulosa and theca cells were isolated and cultured. Cell nature was performed by immunocytochemistry. PFOS and PFOA effect on steroid secretion was analyzed by chemiluminescence. In the present study, alterations in steroidogenic secretion were found when administering PFOS (0.12, 1.2, 12, 120 or 240µM) or PFOA (0.012, 0.12, 1.2, 12 or 24µM) to theca and granulosa cells. When theca and granulosa cells were stimulated with 500ng/mL LH or 500ng/mL FHS, respectively and immediately followed with 1.2µM of PFOS or PFOA, the perfluorinated compounds inhibited the secretion of steroid hormones in both stimulated cell types. The results indicate that PFOS and PFOA act on steroidogenic ovarian cells as endocrine disruptors, which could affect the dependent functions of sexual steroids.

Intima media thickness in children undergoing dialysis.

BACKGROUND: Uremic vasculopathy, including vascular calcification, increases the risk for cardiovascular disease and mortality in chronic kidney disease (CKD) patients. We have investigated the prevalence and factors associated with vasculopathy in children undergoing peritoneal dialysis (PD) or hemodialysis (HD) in a single center. METHODS: Common carotid intima media thickness (cIMT) and its relation with demographics, biochemical parameters and medication was analyzed in 60 patients (mean age 12.9 ± 3.4 years; 27 girls) treated with PD (n = 31) or HD (n = 29) for 34 ± 34 months. Patients were divided into two groups: normal cIMT and increased cIMT. RESULTS: Mean levels of calcium, phosphate and calcium/phosphate product were in the normal range, the but parathyroid hormone level, 729 ± 670 pg/mL, was higher than the National Kidney Foundation Kidney Disease Outcome Quality Iniative (K/DOQI) recommendations. Twenty-nine patients had increased cIMT, which was associated with time on dialysis of >2 years, hypercalcemia, higher daily dose of calcitriol and HD (vs. PD). In the multivariate analysis, accounting for time on dialysis, HD persisted as a risk for increased cIMT. CONCLUSIONS: The prevalence of increased cIMT in children on dialysis is similar to that reported in adults with CKD and increased with time on dialysis. HD was associated with increased cIMT, independently of time on dialysis; however, the results should be interpreted with caution due to the possible impact of confounding factors. These results underline the need to monitor and, if possible, prevent and treat increased cIMT in children on dialysis.

[Design of a HACCP plan for the industrial process of frozen sardines]. / Diseño de un plan HACCP en el procesamiento industrial de sardinas congeladas.

The Hazard Analysis and Critical Control Point (HACCP) is a system to identify, assess and control the hazards related with production, processing, distribution and consumption in order to get safe food. The aim of this study was to design a HACCP plan for implementing in processing line of frozen whole sardine (Sardinella aurita). The methodology was based in the evaluation of the accomplishment of the pre-requisite programs (GMP/SSOP in a previous study), the application of the principles of the HACCP and the sequence of stages settles down by the COVENIN Venezuelan standard No 3802. Time-temperature was recorded in each processing step. Histamine was determined by VERATOX NEOGEN. Results showed that some sardine batches arrived to the plant with high time-temperature records, finding up to 5 ppm of histamine due to the abuse of temperature during transportation. A HACCP plan is proposed with the scope, the selection of the team, the description of the product and the intended use, the flow diagram of the process, hazard analysis and identification of CCP, monitoring system, corrective actions and records. The potential hazards were identified as pathogen growth, presence of histamine and physical objects in the sardines. The control measures of PCC are referred as control of time-temperature during transportation and processing, monitoring of ice supplies and sanitary conditions in the process.

Diseño de un plan HACCP en el procesamiento industrial de sardinas congeladas / Design of a HACCP Plan for the industrial process of frozen sardines

El Análisis de Peligros y Puntos de Control Críticos (HACCP) es un sistema para identificar, evaluar y controlar los peligros relacionados con producción, procesamiento, distribución y consumo a fin de obtener alimentos inocuos. El objetivo de esta investigación fue diseñar un plan HACCP para implementarlo en la línea de sardina (Sardinella aurita) entera congelada. La metodología se basó en la evaluación del cumplimiento de los programas pre-requisitos (POES/BPF en estudio previo), aplicación de los principios del HACCP y la secuencia de etapas establecidas por la norma venezolana COVENIN N° 3802. Se efectuaron registros de tiempo y temperatura en cada etapa del proceso. Se determinó histamina mediante VERATOX® NEOGEN. Los resultados mostraron que algunos lotes de sardinas llegaron a la planta con altos registros de tiempo-temperatura, encontrándose hasta 5 ppm de histamina debido a abuso de temperatura durante el transporte. Se propone un plan HACCP con el alcance, selección del equipo, descripción del producto y su uso previsto, diagrama de flujo del proceso, análisis de peligros, identificación de PCC y límites críticos, sistema de vigilancia, acciones correctivas, verificación y registros. Los peligros potenciales hallados fueron el crecimiento de patógenos, presencia de histamina y objetos físicos en las sardinas. Las medidas de control de los PCC se refieren al control de tiempo-temperatura durante el transporte y procesamiento, vigilancia del suministro de hielo y de las condiciones de saneamiento en el proceso.

The Hazard Analysis and Critical Control Point (HACCP) is a system to identify, assess and control the hazards related with production, processing, distribution and consumption in order to get safe food. The aim of this study was to design a HACCP plan for implementing in processing line of frozen whole sardine (Sardinella aurita). The methodology was based in the evaluation of the accomplishment of the pre-requisite programs (GMP/SSOP in a previous study), the application of the principles of the HACCP and the sequence of stages settles down by the COVENIN Venezuelan standard N° 3802. Time-temperature was recorded in each processing step. Histamine was determined by VERATOX® NEOGEN. Results showed that some sardine batches arrived to the plant with high time-temperature records, finding up to 5 ppm of histamine due to the abuse of temperature during transportation. A HACCP plan is proposed with the scope, the selection of the team, the description of the product and the intended use, the flow diagram of the process, hazard analysis and identification of CCP, monitoring system, corrective actions and records. The potential hazards were identified as pathogen growth, presence of histamine and physical objects in the sardines. The control measures of PCC are referred as control of time-temperature during transportation and processing, monitoring of ice supplies and sanitary conditions in the process.

[Evaluation of prerequisites programs for a HACCP plan for frozen sardine plant]. / Evaluación de los programas pre-requisitos del plan HACCP en una planta de sardinas congeladas.

Good manufacturing practices (GMP) and sanitation standard operating procedures (SSOP) are prerequisites programs for the application of the Hazard Analysis and Critical Control Point (HACCP) system as a food safety approach during processing. The aim of this study was to evaluate GMP/SSOP prerequisites in processing line of frozen whole sardine (Sardinella aurita). The GMP compliance was verified according to a standard procedure of the Ministry for the Health of Venezuela, and the SSOP were assessed according to a checklist proposed by the FDA. GMP and SSOP were evaluated following a demerit-based approach. A percentage value was calculated and referred to as sanitary effectiveness. Results indicated that the plant had a good level of compliance with GMP from assessment of buildings and facilities, equipment and tools, hygienic requisites of the production, assurance of the hygiene quality, storage and transportation, and the percentage of sanitary effectiveness was 84%. The level of compliance for SSOP was 53,12% with demerits found in all assessed aspects consisting of inexistent guidelines, lack of control in the sanitary plan and lack of leadership in applying corrective actions. Thus, an improvement in the plant sanitation program was designed targeting SSOP.

Evaluación de los programas pre-requisitos del plan HACCP en una planta de sardinas congeladas

Las buenas prácticas de fabricación (BPF) y los procedimientos operativos estándares de saneamiento (POES) en planta son considerados los pre-requisitos esenciales para la implementación del sistema de análisis de peligros y puntos de control crítico (HACCP) como una herramienta para la inocuidad de alimentos durante su procesamiento. El objetivo de esta investigación fue la evaluación de las BPF/POES en una línea de sardina (Sardinella aurita) entera congelada. Se verificó el cumplimiento de las BPF mediante la planilla de evaluación del MSAS (Ministerio de Salud) de Venezuela y de los POES a través de un cuestionario propuesto por la FDA. Las BPF y los POES fueron evaluados en base a deméritos, se obtuvo un valor en porcentaje por cada pre-requisito y fue referido como efectividad higiénica. Los resultados obtenidos de la evaluación de las BPF indicaron que la planta cumple con la mayoría de las condiciones de edificaciones e instalaciones, equipos y utensilios, requisitos higiénicos de la producción, aseguramiento de la calidad higiénica, almacenamiento y transporte, obteniendo una efectividad higiénica satisfactoria de un 84%. El nivel de cumplimiento de los POES fue de un 53,12% con deméritos en todos los aspectos evaluados, debido a la inexistencia de un documento guía, carencia de controles en el plan de saneamiento y de liderazgo en ejecutar acciones correctivas. Por lo tanto, se diseñó un programa de control sanitario basado en los POES.

Evaluation of prerequisites programs for a HACCP plan for frozen sardine plant. Good manufacturing practices (GMP) and sanitation standard operating procedures (SSOP) are prerequisites programs for the application of the Hazard Analysis and Critical Control Point (HACCP) system as a food safety approach during processing. The aim of this study was to evaluate GMP/SSOP prerequisites in processing line of frozen whole sardine (Sardinella aurita). The GMP compliance was verified according to a standard procedure of the Ministry for the Health of Venezuela, and the SSOP were assessed according to a checklist proposed by the FDA. GMP and SSOP were evaluated following a demerit-based approach. A percentage value was calculated and referred to as sanitary effectiveness. Results indicated that the plant had a good level of compliance with GMP from assessment of buildings and facilities, equipment and tools, hygienic requisites of the production, assurance of the hygiene quality, storage and transportation, and the percentage of sanitary effectiveness was 84%. The level of compliance for SSOP was 53,12 % with demerits found in all assessed aspects consisting of inexistent guidelines, lack of control in the sanitary plan and lack of leadership in applying corrective actions. Thus, an improvement in the plant sanitation program was designed targeting SSOP.

Sympathetic pharmacological denervation in ageing rats: effects on ovulatory response and follicular population.

The present study analyses the participation of ovarian innervation during reproductive senescence. We use the model of acute peripheral pharmacological sympathetic denervation with guanethidine in young (3 months old), middle-aged (12 months old) or old (18 months old) rats with spontaneous or induced ovulation. Ovarian levels of norepinephrine (NE) were measured by HPLC and the oestrous cycle, the number of ovulating animals and the percentage of atretic follicles were also assessed. Aged animals showed a progressive reduction in ovulatory capacity and an increase in ovarian NE content. Acute denervation increased the percentage of healthy follicles in 12- and 18-month-old rats compared with control adult animals. Combined treatment of denervation plus stimulation with gonadotrophins doubled the number of ova shed in young adult rats and restablished a partial ovulation in 12-month-old rats. The results suggest that ovarian noradrenergic innervation plays a modulator role in ovarian physiology during the ageing ovary process. The action of ovarian noradrenergic innervation seems to be associated with folliculogenesis and the ovarian response to gonadotrophins.

Effects of injecting thymulin into the anterior or medial hypothalamus or the pituitary on induced ovulation in prepubertal mice.

UNLABELLED: In prepubertal mice, subcutaneous thymulin injection before equine chorionic gonadotrophin (eCG) treatment simulates ovulation; seemingly, the thymulin could be acting at the hypothalamus-pituitary axis level. OBJECTIVE: This study was designed to analyze the effects of injecting thymulin into the hypothalamus or pituitary on induced ovulation of prepubertal mice. METHOD: Female mice, 19 days old, were anesthetized with ether and injected with saline solution or thymulin into the anterior or medial hypothalamus or the pituitary and treated with eCG when 20 days old. The ova shed were counted and serum concentrations of 17beta-estradiol were measured. In the ovaries, the morphometrical analysis was performed and the atresia evaluated. RESULTS: Ether anesthesia treatment blocked eCG-induced ovulation in almost all animals. Mice anesthetized and treated with eCG and gonadotrophin-releasing hormone (GnRH) or human chorionic gonadotrophin (hCG) ovulated a full quota of ova. Injecting saline solution into the anterior or medial hypothalamus or the pituitary did not reduce the blocking effects of ether anesthesia on induced ovulation, but the incidence of atretic follicles was higher. Injecting thymulin directly into the anterior hypothalamus did not restore ovulation, nor diminish the number of atretic follicles. In contrast, injecting thymulin into the medial hypothalamus restored the ovulation ratio and decreased the percentage of atretic follicles. Similar results were obtained by injecting thymulin into the pituitary, though thymulin treatment in the pituitary resulted in a higher number of ova shed and lower follicular atresia. CONCLUSION: The present results suggest that thymulin acts at the medial hypothalamus level, facilitating the release of GnRH and at the pituitary level regulating gonadotrophin release.

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle.

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.