RESUMEN
BACKGROUND: Mitochondrial DNA (mtDNA) copy number is associated with tumor activity and carcinogenesis. This study was undertaken to investigate mtDNA copy number in papillary thyroid cancer (PTC) tissues and to evaluate the risk of PTC development. The clinicopathological features of patients and mtDNA copy number were correlated. The value of mtDNA copy number was evaluated as a biomarker for PTC. METHOD: DNA was extracted from 105 PTC tissues and 67 control thyroid tissues, and mtDNA copy number mtDNA oxidative damage were determined using qPCR techniques. RESULTS: Overall, the relative mtDNA copy number was significantly higher in PTC patients (p < 0.001). The risk of developing PTC increased significantly across the tertiles of mtDNA copy number (p trend < 0.001). The higher the mtDNA copy number tertile, the greater the risk of developing PTC. Patients with follicular variants had an odds ratio of 2.09 (95% CI: 1.78-2.44) compared to those with classical variants (p < 0.001). The level of mtDNA oxidative damage in PTC was significantly elevated compared to controls (p < 0.001). The ROC analysis of mtDNA copy number indicated an area under the curve (AUC) of 77.7% (95% CI: 0.71 to 0.85, p < 0.001) for the ability of mtDNA copy number z-scores in differentiate between PTC and controls. CONCLUSION: Our results indicated that the augmentation of mtDNA content plays a significant role during the initiation of thyroid cancer, and it might represent a potential biomarker for predicting the risk of PTC.
Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , ADN Mitocondrial/genética , Masculino , Femenino , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Factores de Riesgo , Biomarcadores de Tumor/genética , Pronóstico , Estudios de SeguimientoRESUMEN
OBJECTIVE: One in every three diagnosed malignancies is skin cancer, making it the most prevalent type of cancer in the world. As skin cancer is not commonly reported in Kuwait, this study was conducted to analyze the clinicopathological characteristics of nonmelanoma skin cancers (NMSC), primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), during the last 13 years in a tertiary dermatology center in Kuwait. MATERIALS AND METHODS: Data were searched for patients with NMSC, primarily BCC and SCC, from 2010 to 2022. A retrospective review was conducted and descriptive data analysis was performed. RESULTS: Of 7,645 cases, a total of 146 patients had NMSC. The patient's average age was 64.9 years. 123 cases (84.2%) had BCC, whereas 23 (15.8%) had SCC. Most of the tumors were seen on the face (35.6%), scalp (20.8%), and nose (17.8%), followed by the back (6.2%), trunk (5.5%), and ear (5.5%). Well-differentiated Cutaneous SCCs were detected in 82.6% of cases. Ulceration was observed in (21.9%) of tumors. The nodular BCC subtype was observed in 50.4% of patients. CONCLUSION: BCC is the most common type of NMSC detected in Kuwait, with the scalp and face being the most common sites of involvement. Any suspicious lesions should be biopsied to rule out skin malignancy.
RESUMEN
INTRODUCTION: This study investigates and compares the relative telomere length (RTL) outcome of high-risk (hr) human papillomavirus (HPV)-infected normal, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) cervical samples to HPV-free normal cervical samples. METHODS: This study used archived cervical samples and obtained cytology and histology data. HPV genotyping was conducted using Sanger sequencing and RTL was performed using real-time quantitative polymerase chain reaction. RESULTS: This study investigated 287 cervical samples, including 100 normal and hr-HPV-negative samples from the control group, 44 normal and hr-HPV-infected samples, and 143 SIL and hr-HPV-infected samples. The RTL in hr-HPV-infected samples, including the SIL and normal sample groups, were significantly longer than that in the control group. RTL in HSIL (5.13 ± 3.22) and LSIL (2.86 ± 2.81) were significantly different (P < 0.001). The RTL of cervical intraepithelial neoplasia (CIN1) lesion (3.53 ± 2.53) differed significantly (P < 0.001) when compared to CIN2 and CIN3 lesions combined. The risk of developing cervical cancer was associated with RTL and was decreased with RTL. CONCLUSION: This study revealed the strong potential of the RTL test in identifying women at risk of developing cervical cancer.
RESUMEN
The majority of cervical cancer cases are due to human papillomavirus (HPV) infection. However, certain cases of cervical cancer are not caused by HPV. Recent studies have shown a link between altered mitochondrial DNA (mtDNA) copy number, an indicative measure of mitochondrial dysfunction, and cervical cancer in women who test positive for HPV. However, the role of the mtDNA copy number in HPV-negative cervical cancer has remained elusive. In the present study, the mtDNA copy number was determined using quantitative PCR as the ratio between mtDNA and nuclear DNA in 287 ThinPrep cervical samples, including 143 cases with cervical abnormalities and 144 control subjects with high-risk (hr)-HPV positive or HPV-negative status. In an overall analysis of cases categorized based on the cytology diagnosis into squamous cervical carcinoma/high-grade squamous intraepithelial lesions (SCC/HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal controls, the mtDNA copy number was significantly higher in all cases compared to the controls and a higher mtDNA copy number was observed in SCC/HSIL compared to LSIL cases. In the stratification analyses based on hr-HPV positive and HPV-negative status, an increased mtDNA copy number was observed in the cases compared with the controls regardless of their HPV status (P<0.05). When cases with cervical abnormalities were categorized based on histological diagnosis into cervical intraepithelial neoplasia (CIN)2/CIN3 and CIN1, an overall analysis indicated an increased mtDNA copy number in CIN2/CIN3 compared to CIN1 (P=0.01). Stratification analyses of these cases based on HPV status revealed a higher mtDNA copy number in CIN2/CIN3 compared to CIN1 regardless of HPV infection (P<0.05). These results showed that an elevated mtDNA copy number in subjects with cervical abnormalities was not influenced by the HPV status and suggested the possibility of its role in the progression of cervical cancer. The increased mtDNA copy number may be an adaptive response mechanism to compensate for mtDNA oxidative stress and energy deficiency, possibly induced by HPV infection and other environmental exposures.
RESUMEN
OBJECTIVE: This study was undertaken to evaluate the performance of FAM19A4 and hsa-mir-124-2 hypermethylation as a triage tool for women who are at risk of developing cervical cancer or high-grade cervical cancer precursor lesions by taking into consideration the cytology report, histology diagnosis, and human papillomavirus (HPV) status. METHODS: A total of 330 cervical ThinPrep samples were retrospectively collected and used for DNA isolation. HPV DNA was detected by real-time polymerase chain reaction (PCR), and HPV genotypes were identified by Sanger-based sequencing. DNA extracts were bisulphite-treated, and hypermethylation of FAM19A4 and hsa-mir-124-2 genes was detected by a quantitative methylation-specific PCR (qMSP) test using the QIAsure Methylation assay. RESULTS: Hypermethylated genes were detected in 27 (9.6%) cervical samples, mostly found in women diagnosed with high-grade squamous intraepithelial legions (77.8%) or cervical intraepithelial neoplasia grade 3 (CIN3) (72.7%). The sensitivity and the specificity of the qMSP test for predicting CIN3 lesions among women with high-risk HPV was 75% and 91%, respectively. DISCUSSION/CONCLUSION: There was a significant correlation between high-grade cervical cancer precursor lesions and detection of hypermethylated genes in samples positive for high-risk HPV. Our results suggest that the QIAsure Methylation test can be used as a triage tool to identify women at risk for cervical cancer progression.
Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Estudios Retrospectivos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Displasia del Cuello del Útero/patología , Metilación de ADN/genética , Reacción en Cadena de la Polimerasa , Papillomaviridae/genética , Detección Precoz del CáncerRESUMEN
AIM: This study was aimed at determining the distribution of type-specific human papillomavirus (HPV) in men with cutaneous warts and correlating this with the clinical and morphological presentation of warts. METHODS: Cutaneous wart samples were obtained from 167 adult men presenting to a dermatology clinic. The tissues were fixed and screened for HPV DNA using real-time PCR. The HPV genotype was determined by PCR-based sequencing. RESULTS: Nine different HPV genotypes were detected, comprising 6 from the α genus (HPV2, 6, 27b, 57b, 57c, and 94), 2 from the γ genus (HPV4 and 65), and HPV1a from the mu genus. Single HPV infection was encountered in 93.4% of the patients, whereas multiple infections were encountered in only 6.6%. The prevalence of HPV27b was highest among four body sites, followed by HPV57c, 1a, and 2. HPV1a was the most common genotype encountered in multiple infections, followed by HPV27b. Patient age, the number of warts, the duration of the presence of warts, and contact with people who have warts were not predictors of wart location. However, a high number of patients with palmar or common body warts had wart sizes of <1 cm. CONCLUSIONS: This study shows that genus α HPV types are detected in about 82% of patients with cutaneous warts.
Asunto(s)
Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Verrugas/epidemiología , Verrugas/virología , Adolescente , Adulto , Factores de Edad , Anciano , Estudios Transversales , ADN Viral , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: This study was undertaken to determine the distribution of type-specific human papillomavirus (HPV) in external anogenital warts, and the correlation with clinical presentation of warts and demographic data of patients. METHODS: Genital warts specimens were obtained from 129 men and 27 women attending a dermatology clinic, who had been advised surgical excision. The tissues were fixed and screened for HPV DNA by using real-time PCR. HPV genotype was determined by PCR-based sequencing. RESULTS: Sixteen different HPV genotypes were detected, comprising 4 oncogenic HPV genotypes (16, 18, 33, 38), 2 low-risk HPV types (LR) (6, 81), HPV 9, and other types associated with common warts (1a, 2, 4, 7, 27b, 27, 57b, 57c, 65). Oncogenic HPV types were found in 34.62% of patients, LR HPV types in 14.4%, HPV 9 in 0.64%, and common warts type in 50.6%. The prevalence of HPV infection with a single type was 88.4, 9.0% for two types, and 2.6% for three types. Multiple logistic regression model showed that age, gender, nationality, number of warts, size of each wart, and positive history of wart in sexual partner, were not predictors of HPV type. However, patients with anogenital warts of one to six months duration were three times more likely to have oncogenic HPV infection compared to those with less than one month. CONCLUSIONS: This study shows that oncogenic HPV types are detected in around 35% of patients with genital warts, and are prevalent in warts of one to six months duration.
Asunto(s)
Condiloma Acuminado/diagnóstico , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Adolescente , Adulto , Condiloma Acuminado/virología , Estudios Transversales , ADN Viral/genética , ADN Viral/metabolismo , Femenino , Genotipo , Humanos , Kuwait/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to examine gynaecological infectious agents observed in conventional and modified Papanicolaou cervical smears (CS) at a tertiary care hospital in Kuwait. METHODS: This retrospective study analysed 121,443 satisfactory CS samples collected between 1997-2014 at the Mubarak Al-Kabeer Hospital, Kuwait. Conventional CS samples were obtained between 1997-2005, while modified CS were obtained between 2006-2014 following the introduction of ThinPrep® testing (Hologic Corp., Bedford, Massachusetts, USA). All samples were initially screened by cytoscreeners before being analysed by cytopathologists to determine the presence of specific infectious agents. RESULTS: Overall, 8,836 (7.28%) of the cervical samples had infectious agents; of these, 62.48% were conventional and 37.52% were modified CS samples. The most frequently observed infectious agents were Candida species (76.05%), Trichomonas vaginalis (9.72%), human papillomavirus (HPV; 9.3%), Actinomyces-like organisms (3.23%), Chlamydia trachomatis (1.27%) and the herpes simplex virus (HSV; 0.43%). There were significantly more cases of Candida species, HPV-associated changes, C. trachomatis, T. vaginalis and Actinomyces-like organisms detected in conventional compared to modified CS samples (P <0.050 each). However, there was no statistically significant difference in the frequency of HSV-associated changes (P = 0.938). The presence of two infectious agents in the same sample was identified in 0.87% of samples. CONCLUSION: Among CS samples collected during an 18-year period, Candida species were most frequently detected, followed by T. vaginalis and HPV. The identification of potential infectious agents is a valuable additional benefit of Papanicolaou smear testing.
Asunto(s)
Enfermedades Transmisibles/diagnóstico , Actinomicosis/diagnóstico , Actinomicosis/epidemiología , Adolescente , Adulto , Candidiasis/diagnóstico , Candidiasis/epidemiología , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Enfermedades Transmisibles/epidemiología , Femenino , Humanos , Kuwait/epidemiología , Persona de Mediana Edad , Prueba de Papanicolaou/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Prevalencia , Estudios Retrospectivos , Centros de Atención Terciaria/organización & administración , Centros de Atención Terciaria/estadística & datos numéricos , Vaginitis por Trichomonas/diagnóstico , Vaginitis por Trichomonas/epidemiologíaRESUMEN
OBJECTIVES: This study aimed to analyse trends in epithelial cell abnormalities (ECAs) in cervical cytology at a tertiary care hospital in Kuwait. METHODS: ECAs in 135,766 reports were compared over three seven-year periods between 1992 and 2012. Conventional Papanicolaou (Pap) smear tests were used in the first two periods and ThinPrep (Hologic Corp., Bedford, Massachusetts, USA) tests were used in the third. RESULTS: Significant increases in satisfactory smears, atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance/atypical glandular cells (AGUS/AGCs) were seen in the second and third periods (P <0.001). No significant increases were observed among low-grade squamous intraepithelial lesions (LSILs) or high-grade squamous intraepithelial lesions (HSILs) (P >0.05). An increase was noted in carcinomas between the first and second periods although a significant decline was seen in the third (P <0.014). CONCLUSION: Satisfactory smears, ASCUS and AGUS/AGC increased during the study period although no significant increases in LSILs, HSILs or carcinomas were observed.
RESUMEN
Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region.
Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/epidemiología , África del Norte/epidemiología , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama/virología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/virología , Femenino , Neoplasias de Cabeza y Cuello/prevención & control , Neoplasias de Cabeza y Cuello/virología , Humanos , Medio Oriente/epidemiología , Papillomaviridae/clasificación , Vacunas contra Papillomavirus/inmunología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virologíaRESUMEN
Sour cherry seed extract (SCE) was evaluated for its capacity to inhibit lipopolysaccharide-treated human peripheral blood T cells expressing tumor necrosis factor-alpha, and the chemokine interleukin-8. Both proteins are diagnostic biomarkers for inflammatory pathologies. Peripheral blood leukocytes from 11 rheumatoid arthritis (RA) patients and 8 healthy control subjects were co-cultured for 24h in lipopolysaccharide and the extract, then evaluated by flow cytometry for T cell activation and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1) expression. There was a dose-dependent decrease in expression of the immunophenotypes: CD3+TNF-α+, and CD3+IL8+ in cultures from RA patients to a greater extent than in cells from healthy participants. These results suggest that the extract may have a modulatory roll in RA and other inflammatory disorders via the induction of HO-1, thus abating oxidative stress and strengthening regulation of pro-inflammatory signaling pathways.
Asunto(s)
Artritis Reumatoide/inmunología , Hemo-Oxigenasa 1/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Extractos Vegetales/farmacología , Prunus , Linfocitos T/efectos de los fármacos , Adulto , Complejo CD3/inmunología , Células Cultivadas , Femenino , Humanos , Interleucina-8/inmunología , Leucocitos Mononucleares/inmunología , Lipopolisacáridos , Persona de Mediana Edad , Semillas , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVES: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. STUDY DESIGN: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. RESULTS: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. CONCLUSIONS: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , ADN Viral/análisis , Pruebas de ADN del Papillomavirus Humano , Inmunohistoquímica , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Proteínas de Unión a Fosfatidiletanolamina/análisis , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Estudios de Casos y Controles , Cuello del Útero/química , Cuello del Útero/patología , Cuello del Útero/virología , Distribución de Chi-Cuadrado , Sondas de ADN de HPV , Femenino , Pruebas de ADN del Papillomavirus Humano/métodos , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Prueba de Papanicolaou , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Valor Predictivo de las Pruebas , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Adulto Joven , Displasia del Cuello del Útero/química , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.
Asunto(s)
Proteínas de la Cápside/genética , Cuello del Útero/virología , Proteínas Oncogénicas Virales/genética , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/virología , Femenino , Variación Genética , Humanos , Kuwait , Datos de Secuencia Molecular , Mutación Missense , Papillomaviridae/aislamiento & purificación , Análisis de Secuencia de ADNRESUMEN
INTRODUCTION: Human papillomaviruses (HPV) are the most commonly known sexually transmitted agents. Almost all cases of cervical cancer are caused by persistent infection. This study was conducted to ascertain whether there is a difference in HPV load in cervical samples with normal and abnormal cervical cytology reports in Kuwait. METHODOLOGY: HPV-positive abnormal ThinPrep samples (n = 206) and normal ThinPrep samples (n = 120) were taken from women attending gynecology clinics. Real-time PCR was used to measure the viral load for all HPV genotypes. RESULTS: The median normalized viral load in samples with normal and abnormal cytology reports was 0.86 × 10-7 and 4.66 × 10-7, respectively (p = 0.001). Median normalized viral load of high-risk (HR), intermediate-risk (IR) and low-risk (LR) HPV was 4.04 × 10-7, 0.71 × 10-7 and 2.38 × 10-7, respectively, (p = 0.002). CONCLUSIONS: The findings suggest that, in the absence of a proper screening programme in Kuwait, quantification of HPV viral load could be considered as a surrogate virology test to identify women with abnormal cytology. Further population-based prospective studies are needed to include more women with high-grade and invasive carcinoma reports.
Asunto(s)
Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Carga Viral , Adulto , Anciano , Femenino , Humanos , Kuwait , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases. Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 µg/ml SCE. Cultures were evaluated by two-color flow cytometry for percent representation of CD3+ IL8+ and CD3+TNF-α cells which express interleukin-8 (IL-8), and tumor necrosis factor-α, (TNF-α+) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE). SCE dosage ranges of 0.5-100 µg/ml in cell cultures significantly suppressed LPS-increased CD3+TNF-α+ and CD3+IL8+ representation from all participants (p < 0.05), with greater pharmacological effect noted in suppression of CD3+TNF-α+ noted in cells from T2DM patients versus healthy control subjects. These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0.05). Since TNF-α and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Hemo-Oxigenasa 1/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Extractos Vegetales/farmacología , Prunus/química , Semillas/química , Complejo CD3/metabolismo , Células Cultivadas , Diabetes Mellitus Tipo 2/inmunología , Femenino , Humanos , Interleucina-8/metabolismo , Leucocitos Mononucleares/inmunología , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. SUBJECTS AND METHODS: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤10(3) copies/µl, intermediate when the viral load = 10(3)-10(4) copies/µl, and high when the viral load >10(4) copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. RESULTS: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. CONCLUSION: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/genética , ADN Viral/sangre , ADN Viral/orina , Sangre Fetal/virología , Orina/virología , Adolescente , Adulto , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Kuwait/epidemiología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Embarazo , Prevalencia , Carga ViralRESUMEN
This study investigates the distribution of human papillomavirus (HPV) in women with abnormal cervical cytology in Kuwait. Two hundred and ninety-eight (298) abnormal ThinPreps were taken from women seeking routine gynecological care and screened for HPV DNA by real-time PCR. HPV genotyping was determined by PCR-based sequencing. HPV DNA was detected in 152 women (51%), and 29 different HPV genotypes were detected, comprising 16 high-risk (HR) (16, 18, 31, 33, 35, 39, 45, 51, 53, 56, 58, 59, 66, 68, 73, 97), nine low-risk (LR) (6, 11, 54, 61, 74, 81, 90, 102, 106), and four intermediate-risk (IR) (62, 67, 84, 87). HPV16 had the highest prevalence (24.3%), followed by HPV11 (13.8%), HPV66 (11.2%), HPV33 (9.9%), HPV53 (9.2%), HPV81 (9.2%), HPV56 (7.9%) and HPV18 (6.6%). HPV prevalence was 86, 67, and 89% in women with invasive cervical carcinoma (ICC), high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (LSIL), respectively. As for age distribution, 69% of all HPVs were found in women aged 20-29 years, and the HPV incidence rate deceased with increasing age. The proportion of single infections decreased as the severity of the cytological diagnosis increased, while the proportion of multiple infections increased. This study is the first of its type in Kuwait and one of few in the Middle East. The findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. They support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests.
Asunto(s)
Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Femenino , Pruebas de ADN del Papillomavirus Humano , Humanos , Kuwait/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Frotis VaginalRESUMEN
This study was undertaken to determine the prevalence and type specific distribution of human papillomavirus (HPV) in women with normal cervical cytology in Kuwait. The study is the first of its type in Kuwait and one of few in the Middle East. The age specific distribution of HPV types was determined in 3,011 ThinPrep samples taken from women seeking routine gynaecological care. ThinPrep samples were screened for HPV DNA by real-time PCR. The type specific distribution of the viruses was determined by PCR-based sequencing. The results showed that HPV DNA was detected in 71 women (2.4%), and 21 different HPV genotypes were detected, comprising eight high-risk (HR) (16, 31, 33, 53, 56, 58, 66, and 73), seven low-risk (LR) (6, 11, 54, 61, 70, 81, and 90), four intermediate-risk (IR) (67, 82, 83, and 84) and HPV 102 and HPV 106. LR HPV types were found in 71.8% of infected samples, HR types in 32.3%, and IR types in 7%. With regard to age, 40.8% of all HPVs were found in women 30-39 years of age, 29.6% in women 40-49 years of age, 19.7% in women over 50 years and 9.9% in women less than 34 years old. The study shows that the prevalence of HPV infection in Kuwait is among the lowest in the world and suggests that HPV vaccine could prevent the development of HPV associated cervical cancer in 1.39% of young females living in Kuwait. However, more extensive population-based studies should be undertaken before implementing HPV vaccination.
Asunto(s)
Cuello del Útero/virología , Papillomaviridae/fisiología , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Cuello del Útero/patología , Femenino , Genotipo , Humanos , Kuwait/epidemiología , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Prevalencia , Factores de Riesgo , Frotis Vaginal , Adulto JovenRESUMEN
OBJECTIVE: To study the different gynecologic infections seen in cervical smears in Kuwait. STUDY DESIGN: Over a 6-year period (2002-2007), a total of 42,294 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional and ThinPrep (Cytyc Corp. Boxborough, Massachusetts) smears were first screened by cytotechnicians and finally reported by cytopathologists, Smears showing inflammation were analyzed with reference to Kuwaiti women. RESULTS: Of the 41,748 (98.7%) patients with satisfactory smears, inflammatory changes were observed in 17, 593 (42.1%). Specific infection was identified in 2,679 (15.2%) cases, of which 60.8% were Kuwaitis. The infections seen were Candida sp (73.8%), Trichomonsa vaginalis (11.9%), human papillomavirus (HPV99) (8.2%), Actinomyces-like organisms (3.4%), Chlamydia trachomatis (2.2%) and herpes simplex virus (0.5%). No significant difference was found in the proportion of infectious agents among Kuwaiti and non-Kuwaiti women except marginally higher T vaginalis (10.9% vs 13.4%, p = 0.05) among non-Kuwaitis. Candida sp was the most detectable infectious agent in both Kuwaiti (74.6%) and non-Kuwaiti women (72.4%). Chi2 for trend revealed an increasing proportion of smears from Kuwaiti women found with specific infections (p = 0.049) as compared to those of non-Kuwaitis over the years. CONCLUSION: The prevalence of infections identified on cervical smears was found to be almost similar in Kuwaiti and non-Kuwaiti women except for T vaginalis, which was higher among non-Kuwaitis as compared to Kuwaitis (10.9% vs. 13.4%, p = 0.051). The Candida sp was the most detectable infectious agent, 74.6% in Kuwaiti and 72.4% in non-Kuwaiti women, followed by T vaginalis, the second and HPV being the third.
Asunto(s)
Enfermedades de los Genitales Femeninos/epidemiología , Infecciones/epidemiología , Frotis Vaginal , Actinomicosis/epidemiología , Femenino , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/microbiología , Enfermedades de los Genitales Femeninos/parasitología , Enfermedades de los Genitales Femeninos/virología , Humanos , Kuwait/epidemiología , Micosis/epidemiología , Enfermedades Parasitarias/epidemiología , Vaginitis/epidemiología , Vaginitis/microbiología , Vaginitis/parasitología , Vaginitis/virología , Virosis/epidemiologíaRESUMEN
This study investigates the potential value of the nuclear matrix protein NMP179 as a marker of abnormal squamous cells in ThinPrep slides. Forty-six cervical scrapes were collected as cell suspensions and ThinPrep slides were prepared. They were double-immunostained for NMP179 and Cytokeratin 18 (CK18), an endocervical cell marker. The method of analysis adopted for the study was designed to distinguish the abnormal squamous cells from benign epithelial cell so that the percentages of abnormal squamous cells that expressed the marker could accurately be determined. Initially, an attempt was made to identify benign and abnormal cells in the ThinPrep slides on the basis of their morphology and immunostaining patterns. Discrimination between the various types of epithelial cells was incomplete using this approach and a more precise method of discrimination between the different epithelial cell types was carried out using a combination of double immunostaining (NMP179 and CK18) and morphometry using nuclear area and nuclear cytoplasmic ratios. Once the different epithelial cell types had been identified, the specificity and sensitivity of NMP179 were determined. The optimal sensitivity (89.9%) was achieved at the N/C ratio 0.36; however, the specificity of NMP179 was very low for all N/C ratios and ranged from 38.8% to 42.2%.