Evaluation of Dynamic Thiol-Disulfide Balance in Preinvasive Lesions of the Cervix

Author(s):  
Burak Sezgin ◽  
Fatih Pirinççi ◽  
Aysun Camuzcuoğlu ◽  
Eda Adeviye Şahin ◽  
Özcan Erel ◽  
...  

Abstract Purpose: This study aimed to determine the potential clinical use of dynamic thiol disulfide balance in cases with preinvasive lesions of the cervix.Methods: One hundred and sixteen patients with high-grade squamous intraepithelial lesion, one hundred patients with low-grade squamous intraepithelial lesion and one hundred and ten healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, oxidative stress index of the retrieved cases were further analysed.Results: Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p:0.004 and p:0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p:0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p:0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p:0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r:0.420, p<0.001).Conclusion: The analysis of dynamic thiol disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus -related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer.

2014 ◽  
Vol 134 (3) ◽  
pp. 534-539 ◽  
Author(s):  
Adela Carrillo-García ◽  
Sergio Ponce-de-León-Rosales ◽  
David Cantú-de-León ◽  
Verónica Fragoso-Ontiveros ◽  
Imelda Martínez-Ramírez ◽  
...  

2014 ◽  
Vol 66 (1) ◽  
pp. 429-436
Author(s):  
Biserka Vukomanovic-Djurdjevic ◽  
Gordana Basta-Jovanovic ◽  
N. Baletic ◽  
Milica Berisavac ◽  
D. Nenadic ◽  
...  

Genomic integration of high-risk human papilloma virus in the nucleus of cervical epithelial mucosal cells leads to epithelial dysplasia. The aim of this study was to determine the relevance of correlation between epithelial survivin expression and the degree of human papilloma virus (HPV)-induced cervical epithelial dysplasia, and to establish the significance of morphometric analysis of the nuclear area in the assessment of the degree of cervical dysplasia. This retrospective study included 99 women with primary, previously untreated lesions, and colposcopic findings indicating dysplasia, in whom a cytological test by Papanicolaou method was interpreted according to the Bethesda criteria as lowgrade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and atypical squamous cells of undetermined significance (ASCUS). We performed human papilloma virus (HPV) typing by PCR for evidence of viruse types 16, 18, 31, 33. After biopsy of the cervical mucosa, we performed hematoxylin-eosin (H-E) and Periodic Acid Schiff (PAS) staining, and immunohistochemical and morphometric analysis of tissue samples. The control group consisted of 12 women without dysplasia and without a verified infection of cervical high-risk HPV. A high statistical correlation between the degree of dysplasia and expression of survivin was found in patients with different types of cervical dysplasia (p = 0.003). We observed a high statistical difference between the area of nuclei at different degrees of cervical dysplasias (p = 0.000). The high-grade cervical dysplasia had a more than 2-fold higher level of ranking in comparison to low-grade dysplasia, and a more than 10-fold higher ranking than the control group without cervical dysplasia.


Author(s):  
Ojoye N. Briggs ◽  
Kemzi N. Elechi-amadi ◽  
Justice C. Ohaka ◽  
Edna O. Nwachuku ◽  
Bartimaeus S. Ebirien-agana

Aim: This study evaluated the effects of metformin in combination with a herbal capsule (glucoblock) on insulin resistance and oxidative stress index in type 2 diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis on the herbal capsule was done using classical methods. Results: The results revealed the presence of alkaloids (100.31μg/mg), flavonoids (131.45μg/mg), cardiac glycosides (55.93μg/mg) and saponins (61.47μg/mg) in the herbal drug glucoblock. The results showed significantly lower FPG levels in the treatment groups when compared to the diabetic control. Group 3 administered metformin had significantly higher FPG levels compared to the negative control. Group 4 administered the herbal drug glucoblock and group 5 administered a combination of metformin and glucoblock, showed no significant differences in FPG levels when compared to the negative control. The diabetic control had significantly higher FPI levels compared to the negative control and treatment groups. The treatment groups showed no significant differences in FPI levels when compared to the negative control. HOMA-IR was significantly higher in the diabetic control compared to the negative control and treatment groups. Also, HOMA-IR values in the treatment groups showed no significant difference compared to the negative control except for group 3 (metformin), that was significantly higher than the negative control. SOD was significantly lower in the diabetic control, compared to the negative control and treatment groups. There were no significant differences in SOD levels in the treatment groups compared to the negative control. TOS levels in the negative control group and treatment groups were significantly lower, compared to the diabetic control. TAS was significantly lower in the diabetic control and treatment groups compared to the negative control. OSI in the diabetic control was significantly higher, compared to the negative control and treatment groups. Also, the treatment groups had significantly higher OSI compared to the negative control. Conclusion: High fat diet and streptozotocin induction produced significant insulin resistance and oxidative stress in the diabetic rats. Glucoblock was more effective in reducing insulin resistance compared to metformin. The combination showed synergistic drug-herb reaction as glucoblock potentiated the actions of metformin. Both showed antioxidant potential but were not effective in lowering oxidative stress to normal levels. There is need to incorporate antioxidant therapy in the treatment protocol for diabetes mellitus.


2021 ◽  
Vol 12 ◽  
Author(s):  
Takeo Shibata ◽  
Sumit Shah ◽  
Teresa Evans ◽  
Hannah Coleman ◽  
Benjamin J. Lieblong ◽  
...  

Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) β deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR β bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.


2019 ◽  
Vol 152 (3) ◽  
pp. 359-364
Author(s):  
Edward B Stelow ◽  
Erik A Dill ◽  
Jonathan J Davick ◽  
Michael B McCabe ◽  
Vanessa M Shami

ABSTRACT Objectives Although the role of human papillomavirus (HPV) in the development of some carcinomas (eg, anogenital and oropharyngeal squamous cell carcinomas) is nondebatable, there is still significant controversy regarding the relationship of HPV and esophageal squamous cell carcinomas (SCCs). Methods All cases were sampled at or near the gastroesophageal junctions in patients with reflux and/or known Barrett esophagus and appear to have been initially sampled “incidentally.” Patients were all men, aged 56 to 80 years. None had a known history of other HPV-related disease. Results We present four cases of high-grade squamous intraepithelial lesion of the gastroesophageal junction secondary to high-risk HPV that have identical histologic features to similar lesions of the anogenital tract. Conclusions Whether such lesions are at risk for developing into invasive SCC remains unclear.


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