Quercetin Modulates Nrf2 and NF-κB/TLR-4 Pathways to Protect against Isoniazid and Rifampicin Induced Hepatotoxicity in vivo

Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid and rifampicin induced liver injury. We randomly divided Wistar rats into seven groups (n=6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. NRF2 and NF-κB pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of ALT, AST, ALP and bilirubin compared to isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared to the anti-TB drug treated group. Quercetin attenuated anti-TB drug induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators HMGB-1 and IFN-γ, inhibiting activation of the NF-κB/TLR-4 axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Evaluation of estrogen and progesterone receptors and Her-2 expression with grading in the fine-needle aspirates of patients with breast carcinoma

Background: There has been a limited literature with regards to comparison between the pre-operative hormonal/Her-2 neu assessment by immunostaining on fine-needle aspiration (FNA) versus core needle biopsies (CNBs) and their correlation with grading of breast carcinoma. Materials and Methods: Two hundred fifty FNAs and 201 CNBs from 252 patients with breast carcinoma were subjected immunocytochemical/histochemical (ICC/IHC) staining along with the grading by the Robinson cytologic and modified Scarff-Bloom-Richardson scoring systems, respectively. Depending on the material adequacy, IHC was also performed on cell blocks. Sensitivity, specificity, and predictive values of ICC were calculated. The kappa statistics was performed to see the power of the study. Cytologic versus histologic gradings were compared and analysed by percentage analysis. Results: Sensitivity of ICC on FNAs for ER, PR, and Her-2neu was 49%, 28.8%, and 46%, respectively, while specificity was 84.5%, 90.6%, and 86.6%, respectively, with a fair agreement on kappa statistics. Her-2neu positivity on CNB versus FNA had a moderate agreement. Her-2neu staining of 3+ was seen in most of the Grade-2 tumours on FNA. Conclusions: Fairly reliable results on grading and hormonal/Her-2neu status are possible when ICC is performed on qualitatively superior FNA material. This is particularly useful in the management of patients in certain settings like inoperable cases

Recurrent malignant pheochromocytoma with lymph nodal metastasis in a child: A rare case

Malignant pheochromocytoma in children manifesting as local recurrence with multiple lymph nodal metastasis is a rare entity. We report a case of a 14-year-old child with recurrent sporadic malignant pheochromocytoma presenting 8 years after primary surgery with retroperitoneal lymphadenopathy. The child underwent excision of the tumor along with retroperitoneal lymphadenectomy. Histopathology confirmed pheochromocytoma with extensive lymph node metastasis. The patient has no signs of disease recurrence till date. This report supports the long-term follow-up and aggressive surgical approach to remove all foci of tumor in recurrent pheochromocytoma

Inguinal Hernia as an Initial Presentation of Pseudomyxoma Peritonei

Pseudomyxoma Peritonei (PMP) is characterized by presence of abundant extracellular mucin in the peritoneum. Preoperative diagnosis of pseudomyxoma peritonei is difficult due to its varied presentation. We report a case of pseudomyxoma peritonei in a 64-year-old male, who initially presented with right inguinal hernia and then with recurrence as left inguino-scrotal hernia. A debulking surgery including subtotal colectomy, cholecystectomy and splenectomy along with peritonectomy was performed. The left inguino-scrotal hernia was reduced and a left inguinal hernioplasty was performed. This case is reported to highlight that pseudomyxoma peritonei can present as inguinal hernia and therefore, a thorough examination of the hernial contents for mucin should be done

Disseminated kaposi's sarcoma in an HIV-positive patient: A rare entity in an Indian patient

AIDS-associated disseminated Kaposi sarcoma (KS) is a rare entity, especially in India due to the low prevalence of human herpes virus-8 infections in Indian population. Due to its rapid and progressive nature, early diagnosis and institution of highly active antiretroviral therapy is crucial in AIDS-associated KS, with a view to achieving favorable prognosis. We report a case of disseminated KS in an HIV-1 positive patient, who presented with two months history of multiple violaceous patches and plaques over the trunk, bilateral upper limbs, lower limbs, and hard palate. The patient died of recurrent massive pleural effusion before starting antiretroviral therapy. This case is being reported due to the paucity of KS in the Indian literature, especially the disseminated type and to highlight its rapidly progressive course which can be fatal