C-reactive protein as an effector molecule in Covid-19 pathogenesis.

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.

In situ immunopathological events in human cervical intraepithelial neoplasia and cervical cancer: Review.

Neoplasia of the cervix represents one of the most common cancers in women. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. The in-situ expression of several cytokines by uterine epithelial cells and by infiltrating leukocytes occurs during the cervical intraepithelial neoplasia and cervical cancer. Some of these cytokines can prevent and others can induce the progression of the neoplasm. The infiltrating leukocytes also produce cytokines and growth factors relate to angiogenesis, chemotaxis, and apoptosis capable of modulating the dysplasia progression. In this review we analyzed several interleukins with an inductive effect or blocking effect on the neoplastic progression. We also analyze the genetic polymorphism of some cytokines and their relationship with the risk of developing cervical neoplasia. In addition, we describe the leukocyte cells that infiltrate the cervical uterine tissue during the neoplasia and their effects on neoplasia progression.

The SARS-CoV-2 Pandemic in Latin America: the Need for Multidisciplinary Approaches.

Purpose of Review: Acute respiratory infections of viral etiology (ARIVE) constitute one of the most frequent infectious processes among humans. They cause significant morbidity and mortality every year in all age groups and regions of the world. Their etiology is diverse, and seasonal viruses began their journey, at some point, with an episode of expansion before their annual circulation as seasonal agents. The coronavirus disease 2019 (COVID-19) pandemic is a challenge for Latin America. Understanding dynamics is essential for decision making, to reduce the health, economic, and social impacts of the pandemic. Recent Findings: Currently, governments in Latin America have taken measures to mitigate the spread of COVID-19 primarily based on World Health Organization recommendations. However, the potential impact of the virus in Latin America is still unknown. Given the urgency, governments need more accurate estimates of what could happen in Latin America in order to make informed decisions, At the September 20, 2020, cumulative cases 2295 of COVID-19 per 1 million population has been registered in Latin America and the Caribbean. Brazil, Peru, and Chile are the most countries affected by this pandemic, registering a total of cumulative cases per million inhabitants of 21,148, 22,941, and 23,262 respectively. Peru has shown the highest death numbers with 949 per million inhabitants. Summary: The Latin American health authorities should make the most beneficial decisions based in scientific facts for the health and life of citizens, both understood in the broadest and most inclusive sense.Once the epidemic is over, Latin America should begin a profound health reform, at a single and universal health system, integrated and coordinated, where the leading role of the Ministry of Health is resumed, to have a national network of modern, integrated, and excellent quality laboratories for the benefit of the entire society.

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela.

Cervical lesions have been associated with infection by high-risk human papilloma virus (high-risk HPV). In 409 women aged >15 years high-risk HPV lesions were identified. In a cohort of this population persistent infection was compared with cytological, colposcopic, and histological lesions. Cervical scrapes were taken and DNA was isolated. HPV was detected by PCR in the E6/E7 region. Genotyping was performed by PCR nested multiple E6/E7. HPV was detected in a 37.40% (153/409), high-risk HPV in 86% (153/178), HPV18 46.64% (83/178), HPV16 34.28% (61/178). Among these 53.93% (96/178) were multiple infections, and HPV18/16 (30/96) was the most frequent 31.25%. The cytology showed changes in 15% of positive patients. A 49.67% in women positive for HPV infection showed abnormalities in the colposcopic study, a relationship that turned out to be statistically significant ( p < 0.0019 test χ(2)). Among all 85% of the women were younger than 45 years of age. Fifty-seven patients were evaluated 15 months after the base study, with initial prevalence of morbidity 49.12% (28/57) and at the end 10.53% (6/57), showing in 89.29% (25/28) negative for HR-HPV infection, 10.34% (3/28) showed persistence of infection, 17.54% (10/57) presented cytological alterations, with 80% of positivity for HPV, and a regression of 100% (10/10) of the previously identified lesions. With colposcopy, 50% (14/28) presented alterations related to HPV, of these 85.71% (12/14) showed regression of such an alteration. The cumulative incidence for HPV was 10.34% (3/29). The incidence rate was 4.23% (3/71), which is equal to 4.23 new cases of HPV infection per 100 people, per year of follow-up. In conclusion, the present work shows a high frequency of infection by high-risk HPV, with predominance of HPV18 and 16 and in general for multiple infections. Colposcopy was better predictor than the Pap smear for infection. The follow-up study revealed a low percentage of persistent infection, and a high frequency of negativity for viral infection, high regression of cytological and colposcopic lesions, a low cumulative and incidence rate similar to that reported by other Latin American countries and higher than the European countries.

In situ increased chemokine expression in human cervical intraepithelial neoplasia.

Chemokines play a role in tumor-inflammation and angiogenesis that could be involved in tumor progression. Monocyte chemoattractant protein-1 (MCP-1), Interleukin-8 (IL-8) and macrophage inflammatory proteins (MIP) have been identified in tumor tissues of patients with different neoplasms. Therefore, the aim of the current study was to investigate the expressions of MCP-1, IL-8 and MIP-1α, mononuclear leukocyte infiltration and leukocyte/chemokine expressions in cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and controls. MCP-1, IL-8 and MIP-1α expressions and leukocyte infiltration were determined by indirect immunofluorescence in cervix biopsies from CIN patients (n=65) and 7 normal controls. Increased expressions of MCP-1 and IL-8 in CIN were observed. Increment of lymphocyte infiltration and coexpression of CD3/MCP-1 and CD3/IL-8 were found in CIN. CD3/MCP-1 cell percentage was found decreased and CD3/IL-8 percentage increased according to the CIN evolution. MIP-1α remained similar to control values. The increased expression of MCP-1 and IL-8 in cervical neoplasia may lead to tumor progression.

Determinación del virus papiloma humano y virus herpes simple y su posible relación con la presencia y tipo de lesiones preinvasivas del cuello uterino / Determination of Human Papiloma and Herpes Simplex Viruses and Their Possible Relation to the Presence and Type of Preinvasive Lesions on the Uterine Cervix

El Cáncer (Ca) de Cuello Uterino (Cu) persiste como un problema de salud pública a nivel mundial. Entre los agentes infecciosos más estudiados que se han relacionado con los procesos neoplásicos, están los virus, y entre ellos el herpes y el papiloma. Esta investigación se realizó para determinar el Virus Papiloma Humano (VPH) y el Virus Herpes Simple (VHS) y su posible relación con la presencia y tipo de lesiones preinvasivas de Cu. Se seleccionaron 65 muestras de tejido de Cu con lesiones de pacientes de sexo femenino y 10 controles aparentemente sanas, para la detección del VPH y VSH. Se utilizó el método de PCR e Hibridación para la genotipificación del VPH. Se observó un 15,38% de positividad para VPH y un 20% para VSH, un caso de coinfección en una paciente con lesión intraepitelial de alto grado (LIEag), demostrándose una diferencia significativa entre las pacientes VPH positivo con LIEag respecto a aquellas con lesiones intraepiteliales de bajo grado (LIEbg). La mayoría de los casos positivos para VHS se detectaron en pacientes con LIEbg. Se demostró una correlación significativa entre el tipo de lesión y la presencia de genotipos de alto y bajo riesgo del VPH.

Cervical cancer persists as a public health problem worldwide. Among the most studied infectious agents that have been associated with neoplasic processes are viruses, including herpes and papilloma. This research was carried out in order to determine the possible relation between infection with herpes simplex virus (HSV) and human papilloma virus (HPV) and the presence and type of pre-invasive cervical lesions. Sixty-five samples of cervical tissue with lesions and ten apparently healthy controls were selected from female patients for the detection of HSV and HPV. PCR and hybridization (HC2) methods were implemented for genotyping HPV. For HPV, 15.38% were positive while for HSV, 20.0%. There was one case of co-infection in a patient with a high grade intraepithelial lesion (HSIL), showing a significant difference between HPV-positive patients with HSIL compared to women with LSIL, low grade intraepithelial lesions. Most of the HSV positive cases were detected in patients with LSIL. A significant correlation was proved between the type of lesion and the presence of high and low risk HPV genotypes.

Amplification of human papillomavirus early genes for detection of nine genotypes in Venezuelan women / Amplificación de genes tempranos del virus del papiloma humano para la detección de nueve genotipos en mujeres venezolanas

Genotyping of human papillomavirus (HPV) by molecular methods may enhance assessment information for screening and following of cervical infection. In this study, cervical samples were obtained from 250 women, along with colposcopic and cytological evaluations. A Nested-PCR-Multiplex assay was used for HPV detection and genotyping for HPV E6/E7 early regions. Infection with HPV was detected in 26.0% of the samples, with 98.46% positive for at least one genotype. High-risk HPVs were identified in 98.44%. HPV18 infection was detected in 76.92% of samples and HPV16 in 36.92%, whether as individual or as multiple infections. These infections were seen more frequently in women under 35 years of age (64.7%). The Pap-smear examination showed that 16.92% (11/65) of the samples had cervical changes suggesting HPV infection, whereas the colposcopic evaluation was suggestive of HPV infection in 47.69% (31/65) of DNA-HPV positive samples. There was a high frequency of high-risk HPV genotypes, particularly HPV18, alone or in multiple-type infections. Colposcopy findings showed to have a high predictive value for the diagnosis of HPV infection. The results reflect that over 50% of HPV-positive patients had a normal colposcopy and/or cytology, highlighting the importance of including HPV testing along with genotype identification in routine gynecological evaluations.

La genotipificación de virus del papiloma humano (VPH) por métodos moleculares puede proveer información valiosa para el monitoreo y seguimiento de la infección cervical. Se estudiaron muestras cervicales obtenidas a partir de 250 mujeres, en quienes se realizó, simultáneamente, evaluación citológica y colposcópica. Un ensayo de PCR, en formato Nested-múltiple para las amplificación de la región temparana E6/E7, fue realizado para la detección y genotipificación viral. La infección por VPH se detectó en 26,0% de las muestras, de las cuales, un 98,46% fue positivo para al menos uno de los genotipos probados; los VPH de alto riesgo se identificaron en un 98,44%. Los genotipos más frecuentes fueron VPH18 con un 76,92%, y VPH16 con un 36,92%, ya sea como infecciones individuales o múltiples. En cuanto a la edad, estas infecciones fueron más frecuentes en mujeres menores de 35 años, con un 64,7%. Los resultados citológicos mostraron que 16,92% (11/65) de las muestras cervicales tenían cambios sugestivos de infección por VPH; mientras que la evaluación colposcópica fue sugestiva de la infección por VPH en 47,69% (31/65) de las muestras ADN-VPH positivas. Se determinó una elevada frecuencia de los genotipos de VPH de alto riesgo, particularmente VPH18, solo o en infecciones múltiples. Los hallazgos colposcópicos mostraron un elevado valor predictivo para el diagnóstico de la infección por VPH. Los resultados reflejan que más del 50% de las pacientes VPH positivas tenían colposcopía y/o citología normal, evidenciando la importancia de incluir las pruebas de detección e identificación de VPH en la evaluación ginecológica de rutina.

Amplification of human papillomavirus early genes for detection of nine genotypes in Venezuelan women.

Genotyping of human papillomavirus (HPV) by molecular methods may enhance assessment information for screening and following of cervical infection. In this study, cervical samples were obtained from 250 women, along with colposcopic and cytological evaluations. A Nested-PCR-Multiplex assay was used for HPV detection and genotyping for HPV E6/E7 early regions. Infection with HPV was detected in 26.0% of the samples, with 98.46% positive for at least one genotype. High-risk HPVs were identified in 98.44%. HPV18 infection was detected in 76.92% of samples and HPV16 in 36.92%, whether as individual or as multiple infections. These infections were seen more frequently in women under 35 years of age (64.7%). The Pap-smear examination showed that 16.92% (11/65) of the samples had cervical changes suggesting HPV infection, whereas the colposcopic evaluation was suggestive of HPV infection in 47.69% (31/65) of DNA-HPV positive samples. There was a high frequency of high-risk HPV genotypes, particularly HPV18, alone or in multiple-type infections. Colposcopy findings showed to have a high predictive value for the diagnosis of HPV infection. The results reflect that over 50% of HPV-positive patients had a normal colposcopy and/or cytology, highlighting the importance of including HPV testing along with genotype identification in routine gynecological evaluations.

Comparative analysis of three methods for HPV DNA detection in cervical samples / Análisis comparativo de tres métodos para la detección del ADN de VPH en muestras de cuello uterino

High risk HPV infection is considered to play a central role in cervical carcinogenesis. HPV DNA testing has shown to be a very useful tool for screening and following cervical infections. The aim of this study was to compare three methods for HPV DNA detection, along with cytology and colposcopy analysis. Cervical samples were collected from 100 sexually active women in Mérida, western Venezuela. HPV infection was screened using Hybrid-Capture 2 (HC2), L1-Nested-PCR and E6/E7-PCR assays. 40% of the samples (40/100) were HPV positive by at least one of the DNA detection methods. HC2 detected HPV in 12% specimens. L1- and E6/E7-PCRs showed 50% sensitivity and 77% specificity.The agreement rate between HC2 and both PCR assays was 65%. Kappa value showed moderate concordance between HC2 and both PCR methods (κ=0.55; CI 95%). Also moderate concordance was seen when L1- and E6/E7-PCRs were compared (κ=0.48; CI 95%). There was a significant association between the Schiller test and E6/E7-PCR (p=0.006) for HPV infection. An acceptable agreement between all three assays for HPV detection was observed. Nevertheless, different PCR formats need to be further analyzed in order to make the right choice of method for HPV testing.

La infección con VPH de alto riesgo es el principal factor etiológico asociado al desarrollo de carcinogénesis cervical y las pruebas de detección de ADN-VPH han mostrado ser una herramienta esencial para la pesquisa y seguimiento de estas infecciones. El objetivo del estudio ha sido comparar tres métodos para la detección del ADN viral, en combinación con los análisis colposcópico y citológico. Se obtuvieron muestras cervicales de 100 mujeres sexualmente activas, en Mérida, Venezuela. La detección de infecciones por VPH se realizó por Captura Híbrida 2 (CH2) y los ensayos de PCR “L1-Nested-PCR” y “E6/E7-PCR”. 40% de las muestras (40/100) fueron positivas para VPH por al menos uno de los métodos aplicados. 12% de las muestras analizadas fueron positivas para VPH por CH2. Las dos PCR utilizadas mostraron un 50% de sensibilidad y 77% de especificidad. La coincidencia observada entre CH2 y las dos PCR fue del 65%. La determinación del valor Kappa mostró una concordancia moderada entre CH2 y ambos métodos de PCR (κ=0,55; CI 95%). También existió concordancia moderada al comparar las PCR de las regiones L1 y E6/E7 de VPH (κ=0,48; CI 95%). Hubo una asociación significativa entre el resultado del test de Schiller y la PCR E6/E7 (p=0,006) para la infección por VPH. Se determinó una concordancia aceptable entre los tres métodos aplicados para la detección de VPH; sin embargo, las PCR deben ser analizadas en trabajos futuros con el fin de establecer las pruebas más adecuadas para la detección viral.

Comparative analysis of three methods for HPV DNA detection in cervical samples.

High risk HPV infection is considered to play a central role in cervical carcinogenesis. HPV DNA testing has shown to be a very useful tool for screening and following cervical infections. The aim of this study was to compare three methods for HPV DNA detection, along with cytology and colposcopy analysis. Cervical samples were collected from 100 sexually active women in Mérida, western Venezuela. HPV infection was screened using Hybrid-Capture 2 (HC2), L1-Nested-PCR and E6/E7-PCR assays. 40% of the samples (40/100) were HPV positive by at least one of the DNA detection methods. HC2 detected HPV in 12% specimens. L1- and E6/E7-PCRs showed 50% sensitivity and 77% specificity.The agreement rate between HC2 and both PCR assays was 65%. Kappa value showed moderate concordance between HC2 and both PCR methods (kappa=0.55; CI 95%). Also moderate concordance was seen when L1- and E6/E7-PCRs were compared (kappa=0.48; CI 95%). There was a significant association between the Schiller test and E6/E7-PCR (p=0.006) for HPV infection. An acceptable agreement between all three assays for HPV detection was observed. Nevertheless, different PCR formats need to be further analyzed in order to make the right choice of method for HPV testing.

Detección molecular mediante RT-PCR de calicivirus y enterovirus en niños menores de 6 años con síndrome diarreico / Calicivirus and enterovirus molecular detection through RT-PCR in children under 5 years old with diarrheal syndrome

Mundialmente, la diarrea es una de las causas más importantes de morbi-mortalidad en la población. En Venezuela, se reportan anualmente cerca de 480.000 consultas y 706 fallecimientos a causa de diarreas, de las cuales el 32% se registran en el Zulia. Entre los virus con capacidad patogénica involucrados en cuadros diarreicos se encuentran los calicivirus y enterovirus. Con el objetivo de evaluar la prevalencia de estos agentes virales en el municipio Maracaibo, se colectaron 150 muestras de heces diarreicas de niños menores de 6 años, en las que se analizó la presencia de calicivirus y enterovirus mediante RT-PCR. Se observó una mayor prevalencia de infección por enterovirus (31,3%), lo que indica la existencia de posibles problemas de higiene y/o contaminación del agua. Además, se evidenció disminución de la infección por enterovirus con el aumento de la edad, posiblemente por la adquisición de anticuerpos por exposiciones previas al virus. La prevalencia de calicivirus en la población fue baja (3,0%), considerándolos así casos aislados. La ausencia de este virus durante el primer año de vida se ve favorecida por la protección inmunitaria que confiere la alimentación con leche materna. El presente estudio indica que los enterovirus son agentes etiológicos importantes de diarreas en la población infantil estudiada.

Worldwide, diarrhea is one of the most important morbility-mortality causes in the general population. In Venezuela, there are annual reports of around 480,000 consultations and 706 deaths due to diarrhea, 32% of which are registered in Zulia State. Calicivirus and enterovirus are among the viruses with pathogenic capacity involved in diarrheal episodes. With the purpose of evaluating the prevalence of these viruses at the Maracaibo Municipality, we collected 150 diarrheal feces samples from children under 5 years old, and calicivirus and enterovirus presence was determined through RT-PCR. There was a greater prevalence of enterovirus infections (31.3%), which indicates the probable existence of hygiene problems and/or water contamination. There was also evidence of a decrease of enterovirus contamination with age, possible due to the development of antibodies during previous exposure to the virus. Calicivirus prevalence in this population was low (2.9%), and they were considered as isolated cases. Absence of this virus during the first year of life is favored by the immunological protection conferred by maternal breast-feeding. The present study indicates that enteroviruses are important diarrheal etiologic agents in the child population studied.

Increased vascular endothelial growth factor expression, CD3-positive cell infiltration, and oxidative stress in premalignant lesions of the cervix.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in cervical intraepithelial neoplasia (CIN) progression. The occurrence of leukocytes has been documented in CIN; however, their role in VEGF production remains unknown. Oxidative stress has been involved in the progression of malignant neoplasias, but to the authors' knowledge tissue oxidative stress in CIN has not been documented. The objective of the current study was to investigate the expression of VEGF, leukocyte infiltration, leukocyte VEGF expression, and nitrogen/oxygen metabolism in cervical tissues from patients with CIN. METHODS: Indirect immunofluorescence was used to study the expression of VEGF and leukocyte infiltration in cervical samples from 55 patients with CIN and 7 normal controls. Superoxide anion (O(2) (-)) expression was determined by a cytochemical method, and tissue and serum nitric oxide by the Griess reaction. Human papillomavirus (HPV) DNA and HPV types were identified by the hybrid capture 2 HPV DNA test. RESULTS: Increased expression of VEGF was observed related to the progression of CIN. A significant increment of CD3 lymphocytes was found in CIN type 3 (CIN 3) and coexpression of CD3/VEGF and monocyte-macrophage/VEGF in CIN 2 and 3. Increased O(2) (-)-positive cells were found in CIN 2 and 3; however, tissue nitrate-nitrite content remained similar to controls. The incidence of HPV infection was 16% in patients with CIN. No significant differences were observed in the values of HPV-positive or HPV-negative patients. CONCLUSIONS: Different factors leading to cervical neoplasia progression may be involved in the evolution of CIN, and the presence of these factors is most likely not related to the HPV infection status.

Increased number of IL-2, IL-2 receptor and IL-10 positive cells in premalignant lesions of the cervix

Previous studies have shown the involvement of the immune response in the progression of human uterine cervix cancer. The aim of this study was to determine the expression of Interleukin-2 (IL-2), IL-2 receptor (IL-2R) and Interleukin 10 (IL-10) in different grades of cervical intraepithelial neoplasias of the exocervix (CIN 1, 2 and 3), and its relationship with the serum cytokine profiles and human papilomavirus (HPV) infection status. Indirect immunofluorescence was used to study the expression of IL-2, IL-2R and IL-10 in human cervical samples from 50 patients and 9 normal controls. Serum IL-2, IL-2R and IL-10 were measured by ELISA and HPV DNA and HPV types were identified by PCR. Increased number of IL-2, IL-2R and IL-10 positive cells were observed in the cervix from patients with CIN, associated with the grades of dysplasia. A significant correlation was observed between IL-2 and IL-2R (p>0.0001), IL-2 and IL-10 (p > 0,0001), as well as IL-10 and IL-2R (p> 0.0001). Twenty percent of patients were HPV positive and 84 % of those patients were tissue cytokine positive. These results suggest that IL-2, IL-2R and IL-10 tissue expression may play a role in the development of cervical intraepithelial dysplasias.

En previos estudios se ha determinado que la respuesta inmunitaria esta involucrada en la progresión del cáncer del cuello uterino humano. El propósito de este estudio fue determinar la expresión de Interleucina-2 (IL-2), del receptor de IL-2 (IL-2R) e Interleucina 10 (IL-10) en diferentes grados de la neoplasia intraepithelial cervical del exocervix (NIC 1, 2 y 3) y su relación con los niveles séricos de estas citocinas y el estado de infección con el virus del papiloma humano (VPH). Se usó la inmunofluorescencia indirecta para determinar la expresión de IL-2, IL-2R e IL-10 en muestras de tejido cervical procedentes de 50 pacientes y 9 controles. Las concentraciónes de IL-2, IL-2R e IL-10 sérica fueron determinadas mediante ELISA y el ADN del VPH y los tipos de virus mediante PCR. Se encontró aumento del número de células positivas para IL-2, IL-2R e IL-10 en el cervix de pacientes con NIC, asociado al grado de la lesión. Se encontró alta significacia cuando se correlacionó la expresión de IL-2 con IL-2R (p>0.0001), IL-2 con IL-10 (p>0.0001) y la IL-10 con IL-2R (p>0.0001). El 20% de los pacientes fueron VPH positivos y de estos pacientes el 84% tuvieron expresión de citocinas a nivel tisular. Estos resultados sugieren que la expresión tisular de la IL-2, IL-2R y la IL-10 pueden estar involucradas en la progresión de la displasia intraepitelial cervical.

Relación entre el herpes simple tipo 2 y las lesiones preinvasivas de cuello uterino / Relationship between type 2 herpes simples and uterine cervix pre-invasive lesions

Objetivos: Determinar la presencia y relación del virus herpes simple tipo 2 (VHS-2) en mujeres con diferentes gradosde lesiones preinvasivas de cuello uterino. Materiales y métodos: Se estudiaron 176 mujeres con lesiones pre invasivas de cuello uterino y 40 mujeres como grupo control con cuello uterino sano, que asistieron a la consulta ginecológica en diferentes centros de salud, durante los años 2002-2005 en Maracaibo-Venezuela. A las pacientes se les tomó un hisopado del exocervix y una biopsia dirigida del sitio de la lesión por colposcopía. La determinación deVHS-2 se realizó a través de inmunofluorescencia directa. Resultados: La presencia de infección por VHS-2 fue 44/176 (25). El mayor número de VHS-2 se obtuvo en las pacientes con grado de lesión tipo NIC II (66,7). El mayor porcentaje de infección por VHS-2 se determinó en las pacientes que iniciaron sus relaciones sexuales entre los 15 y20 años (34,5), las relaciones sexuales diarias (50), así como relaciones de tipo orogenital fueron consideradas las conductas de mayor riesgo para adquirir la infección. Conclusiones: No se evidenció una relación directa entre VHS-2y la presencia de cáncer. Los factores de riesgo asociados con la infección son similares a otras ITS, y están ligados con la conducta sexual y hábitos propios del individuo.

Objectives: To determine the presence and relationship of type 2 herpes simplex virus (HSV-2) in women with different degrees of pre-invasive cervical lesions. Materials and methods: 176 women with pre-invasive cervical lesions and 40 healthy controls were studied. These women were regular clients of gynecology outpatient clinics in different health centers during the 2002-2005 period in Maracaibo, Venezuela. Subjects underwent an exo-cervical smear and a colposcopy-oriented biopsy of the lesion site. HSV-2 determination was performed using direct immunofluorescence. Results: HSV-2 infection was detected in 44/176 women (25%). The highest figures for HSV-2 were obtained in women with ICN II lesions (66,7%). The highest frequencies of HSV-2 infections were found in women starting sexual life between 15 and 20 years of age (34,5%). Daily intercourse (50%), as well as oral sex, was considered as the most risky behavior for acquiring the infection. Conclusions: No direct relationship between HSV-2 and cancer was evidenced. Risk factors associated with this infection are similar to those for other sexually transmitted diseases, and they are linked with sexual behavior and individual habits.

Virus del herpes simple tipo 2: influencia en el origen de las lesiones premalignas y malignas del cuello uterino / Herpes simplex virus type 2: influence in the origin of premalignant and malignat lesions of uterine cervix

Determinar si la interacción del virus del herpes simple tipo 2 con diferentes factores epidemiológicos, tiene influencia en las lesiones premalignas y malignas del cuello uterino. Ambulatorios de Los Olivos, Crujicito, Salud Maracaibo, La Victoria y la consulta de Patología de Cuello Uterino del Hospital "Manuel Noriega Trigo", (Seguro Social), Maracaibo. Cincuenta y tres pacientes con neoplasia intraepitelial cervical y 10 controles fueron analizados. Se tomó un hisopado cervical para la determinación del virus del herpes simple tipo 2 mediante la técnica de la inmunofluorescencia indirecta y para el virus del papiloma humano por la técnica de la reacción en cadena de polimerasa. La presencia del virus del herpes simple 2-fue del 27,65 por ciento (n=18) de las pacientes. Las pacientes con lesiones premalignas del cerviz (n= 48) y las pacientes del grupo control (n= 10) presentaron un 27,1 por ciento y 30 por ciento de positividad al virus del herpes simple-2, respectivamente. No se encontró ninguna asociación entre el virus del herpes simple -2 y la neoplasia intraepitelial cervical. El virus del herpes simple-2 no está asociado a las lesiones premalignas del cuello uterino

Comportamiento del oxido nítrico sérico en pacientes con hepatitis viral aguda A y B, y crónica C: oxido nitrico como medidor inmunológico / Seric nitric oxide pattern in patients whit viral acute A and B, and chronic C hepatitis: nitric oxide as an immunology response

Diversas investigaciones han señalado al oxido nítrico (NO) como un agente que definitivamente esta implicado en la injuria celular, cronicidad, cirrosis y carcinoma hepático. El objetivo de este estudio fue determinar los concentraciones de nitritos (NO-2) séricos, como índice de generación de oxido nítrico y su comportamiento en pacientes con hepatitis viral aguda A y B, y crónica C. Se incluyeron un total de 80 pacientes, 20 con el diagnostico de hepatitis viral aguda a virus A, 20 con el diagnostico de hepatitis viral aguda a virus B, 20 con el diagnostico de hepatitis viral crónica a virus C y 20 individuos sanos identificados como controles. A todos se les practicó perfil serológico para hepatitis viral y concentraciones séricos de nitritos. La determinación de nitritos séricos en los pacientes y controles demostró diferencia estadísticamente significativa P<.0001 al comparar las hepatitis agudas A y B con los controles; de igual forma hubo diferencia significante al compararlo con hepatitis C en fase crónica. Las concentraciones de nitritos, en los pacientes con hepatitis C crónica, no demostró diferencia significativa al compararlo con los controles (8,65±5.11 Vs. 7.81±3.80nm/ml). Dada la importancia que representa esta molécula en los procesos señalados es necesario futuras investigaciones para aclarar su papel a este respecto, sin embargo, se puede sugerir que el oxido nítrico tiene un papel importante en la defensa antiviral, hecho que se apoya en la concentración sérica significativamente alta que se encontró en el proceso agudo de la enfermedad

[Gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukins 2, 4 and 6 (IL-2, IL-4, IL-6) in cervical-uterine cells of intraepithelial neoplasia: a preliminary report]. / Expresión de interferon gamma (IFN-gamma), factor de necrosis tumoral alfa (TNF-alpha) e interleucinas 2, 4 y 6 ( IL-2, IL-4, IL-6) en células de neoplasias intraepiteliales de cuello uterino: reporte preliminar.

The purpose of this work was to determine the expression of type Th1 cytokines: IL-2 and IFNgamma, and Th2: IL-4 and IL-6, as well as TNF-alpha in patients with precancerous lesions of the uterine cervix and their relationship with the human papiloma virus (HPV). 30 patients with precancerous lesions (NIC 1: 70%, NIC 2: 16.7% and NIC 3: 1.3%) and 9 normal controls were studied. A clinical history, gynecological evaluation, cytology and an uterine biopsy were carried out in each patient and control. PCR was used for the diagnosis of HPV. IFN-gamma expression (positive cells/field) was increased in patients with NIC (5.06 +/- 4.7 vs 0 in the control group; p < 0.05). TNFa was a little higher in pathologycal tissues than in the controls (5.23 +/- 3.63 vs 1.55 +/- 2.65; p < 0.05). IL-2 was higher in pathologycal cases than in the controls (8.73 +/- 5.23 vs 0.33 +/- 1, p < 0.05). IL-4 were expressed in both, patients and controls (6.53 +/- 5.23 vs 5.77 +/- 7.32). IL-6 was also higher in patients (4.63 +/- 3.34 vs 0.77 +/- 2.33; p < 0.05). When the HPV status was considered, only IFN-gamma (p < 0.05) and IL-2 (p < 0.05) were significantly higher in HPV positive patients (n = 4) compared to controls. When HPV+ patients were compared with HPV- patients, only IFNgamma was significant (11.5 +/- 5 vs 4.07 +/- 3.8; p < 0.05). In conclusion, Type Th1 immune response prevails in patients with precancerous lesions, whether they are HPV positive or not.

Expresión de interferón gamma (IFN-g), factor de necrosis tumoral alfa (TNF-a) e interleucinas 2, 4 y 6 (IL-2, IL-4, IL-6) en células de neoplasias intraepiteliales de cuello uterino: reporte preliminar / Gamma interferon (IFN-g), tumor necrosis factor alpha (TNF-a) and interleukins 2, 4 and 6 (IL-2, IL-4, IL-6) in cervical-uterine cells of intraepithelial neoplasia: a preliminary report

El presente estudio fue realizado para determinar la expresión de citocinas tipo Th1: IL-2 y IFN-g, y Th2: IL-4 e IL-6, así como del TNF-a en pacientes con lesiones premalignas del cuello uterino (CU) y su relación con la infección por el Virus del Papiloma Humano (VPH). Se estudiaron 30 pacientes con lesiones pre-malignas del CU; NIC 1: 70 por ciento, NCI 2: 16,7 por ciento y NIC 3: 13,3 por ciento) y 9 controles con CU sanos. A cada paciente se le realizó una historia clínica, evaluación ginecológica que incluyó la toma de la citología cervico-vaginal (CCV) y biopsia de CU para estudio histológico e inmunológico. Se empleó la reacción en cadena de polimerasa (PCR) para el estudio del VPH. La expresión del IFN-g se encontró aumentada en pacientes con respecto al grupo control (5,06 ± 4,7 vs 0 media ± DS; p < 0,05). El TNF-a se expresó discretamente elevado en los diferentes tipos de lesiones con respecto al grupo control (5,23 ± 3,63 vs 1,55 ± 2,65; p < 0,05). La IL-2 se encontró más elevada en los casos patológicos que en los controles (8,73 ± 5,23 vs 0,33 ± 1, p < 0,05). La IL-4 se expresó de manera no significativa en tejidos patológicos al compararlo con los controles (6,53 ± 5,23 vs 5,77 ± 7,32). La expresión de la IL-6 fue más elevada en las pacientes que en los controles (4,63 ± 3,34 vs 0,77 ± 2,33; p < 0,05). Al comparar pacientes VPH positivos con los controles, solo el IFN-g (p < 0,05) y la IL-2 (p < 0,05) fueron significantes. Sólo el IFN-g fue significativo al comparar pacientes con o sin VPH (11,5 ± 5 vs 4,07 ± 3,8 p < 0,007). La respuesta inmunitaria tipo Th1 predomina en las lesiones premalignas, esté presente o no el VPH

[Laboratory diagnosis of patients with exanthematic or febrile syndromes occurring in the Zulia State, Venezuela, during 1998]. / Diagnóstico etiológico de pacientes con exantemas o cuadros febriles atendidos en 1998. Estado Zulia, Venezuela.

BACKGROUND: Exanthematic diseases are a group of syndromes mainly caused by acute viral infections. AIM: To obtain information about the viruses that cause exanthematic diseases in our region. PATIENTS AND METHODS: During 1998, 267 serum samples from patients with an acute rash or patients presenting a febrile syndrome accompanied by enlarged lymph nodes, headache and other symptoms, were collected. Specific antibody of the IgM class (anti-IgM) against Rubella, Measles, Dengue types 1-4 and Cytomegalovirus (CMV) were measured by immunoenzymatic assay (EIA). Epstein-Barr virus (EBV) antibodies were measured by immunofluorescence. RESULTS: An etiologic agent was detected in 208 cases (77.9%). Cases due to Dengue (40.6%) and Rubella (21%) viruses predominated, but the frequency of other agents was also high in specific age groups. The agreement between the clinical suspicion and the laboratory findings varied broadly, from a 100% for suspected Dengue to just a 14.8% for cases of suspected CMV infection. CONCLUSIONS: Dengue was the most common viral exanthematic disease in the Zulia State during 1998.

Concentrations of cytokines, soluble interleukin-2 receptor, and soluble CD30 in sera of patients with hepatitis B virus infection during acute and convalescent phases.

The immunoregulatory roles of interleukin-2 (IL-2), IL-4, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), the soluble form of the IL-2 receptor (sIL-2R), and the soluble form of CD30 (sCD30) were evaluated in patients with hepatitis B virus (HBV) infection. Two groups of subjects were studied: 15 healthy individuals without hepatitis antecedents and 15 patients with HBV infection. Blood samples were taken during the acute and convalescent phases. The analysis of the samples was done by the enzyme-linked immunosorbent assay technique. IFN-gamma and TNF-alpha levels decreased in the convalescent phase. IL-10, IL-2, and sIL-2R levels increased in the acute and convalescent phases, while sCD30 levels increased during the acute phase. The IL-4 concentrations decreased in both phases. During the acute phase, IFN-gamma and TNF-alpha induced increases in IL-2, sIL-2R, IL-10, and sCD30 levels in serum, which allowed the development of immunity characterized by the nonreactivity of the HBV surface antigen, the onset of antibodies to the HBV surface antigen (anti-HBs), and normal alanine aminotransferase levels during the convalescent phase. Increased IL-2 levels during the acute phase would stimulate the activities of NK cells and CD8(+) lymphocytes, which are responsible for viral clearing. The raised sIL-2R levels reveal activation of T lymphocytes and control of the IL-2-dependent immune response. The sCD30 increment during the acute phase reflects the greater activation of the Th2 cellular phenotype. Its decrease in the convalescent phase points out the decrease in the level of HBV replication. The increase in IL-10 levels could result in a decrease in IL-4 levels and modulate IFN-gamma and TNF-alpha levels during both phases of disease, allowing the maintenance of anti-HBs concentrations.