Rutin inhibits carfilzomib-induced oxidative stress and inflammation via the NOS-mediated NF-κB signaling pathway.

BACKGROUND: Carfilzomib (CFZ), a proteasome inhibitor approved by the FDA to treat multiple myeloma, may cause nephrotoxicity. HYPOTHESIS: Rutin is a bioflavonoid with antioxidant properties. We aimed to examine whether rutin protects the kidney from CFZ-induced nephrotoxicity. STUDY DESIGN: This study aimed to demonstrate the effect of rutin on CFZ-induced renal injury via the inhibition of oxidative stress and inflammation. METHODS: Wistar albino rats were divided into six groups (n = 6): Group 1 (normal control; NC) was administered normal saline for 3 weeks; Group 2 (CFZ/toxic group) received CFZ [4 mg/kg, intraperitoneal (i.p.) injection] twice weekly for 3 weeks; Group 3 (standard treatment group) was administered CFZ (4 mg/kg, i.p.) and olmesartan (2 mg/kg, p.o.) for 3 weeks; Group 4 was administered CFZ (4 mg/kg, i.p.) and rutin (10 mg/kg, p.o.) for 3 weeks; Group 5 was administered CFZ (4 mg/kg, i.p.) and rutin (20 mg/kg, p.o.) for 3 weeks; and Group 6 was administered CFZ (4 mg/kg, i.p.) and rutin (40 mg/kg, p.o.) for 3 weeks. We carried out haematological and biochemical analyses, determined oxidative stress, caspase-3 activity, and protein levels, and performed a histopathological evaluation to confirm CFZ-induced nephrotoxicity and its prevention by rutin administration. RESULTS: Exposure to only CFZ significantly (p < 0.05) increased white blood cell (WBC) count, Hb%, and HTC% concentration; however, these features were significantly decreased (p < 0.05) when olmesartan and rutin were administered. CFZ administration significantly decreased (p < 0.0001) the level of antioxidant enzymes; whereas, administration of olmesartan and rutin significantly reversed (p < 0.05) their levels toward the normal range. The levels of caspase-3 enzyme significantly increased (p < 0.001) in the CFZ group and were reduced toward the normal values by olmesartan and rutin administration. Furthermore, the results of NOS-2, NF-κB, IkBa, and IL-17 protein estimation and the histopathological evaluation strengthened our findings that rutin exhibits a protective effect against CFZ-induced nephrotoxicity. CONCLUSION: These findings clearly demonstrate that rutin ameliorates CFZ-induced oxidative stress and inflammation in nephrotoxicity via the NOS-mediated NF-κB signaling pathway.

An Unusual Case of Inflammatory Myofibroblastic Tumor of the Appendix Masquerading as Acute Appendicitis.

Inflammatory myofibroblastic tumor (IMT) is reported virtually in every anatomic location of the body, but most cases are commonly identified in the mesentery and omentum. The etiology of this tumor is unclear with many suggestions of viral, inflammatory, or oncogenic mutational factors that establish it as a clonal neoplasm. Clinical and laboratory workup, including roentgenography, is not usually helpful to reach a pre- or intraoperative diagnosis. Histopathology and immunohistochemistry of the resected specimen provides a definitive answer by the exclusion of a close clinical differential diagnosis of gastrointestinal stromal tumor and many lookalikes. Complete surgical excision with clear margins is the mainstay of treatment. Rare cases have been seen involving the appendix. To the best of our knowledge, only 11 confirmed cases of purely appendiceal IMT have been published in the literature to date.

The tyrosine kinase inhibitor tyrphostin AG126 reduces activation of inflammatory cells and increases Foxp3+ regulatory T cells during pathogenesis of rheumatoid arthritis.

Protein tyrosine kinases are key mediators of the signal transduction cascades that control expression of many genes involved in the induction of inflammation caused by arthritis. Here we investigate the effect of the tyrosine kinase inhibitor tyrphostin AG126 on a mouse model of adjuvant-induced arthritis (AIA). We report that when given at 5mg/kg i.p. every 48h from days 0-21, AG126 exerts potent anti-arthritic effects. Further, we investigated the role of AG126 on the key mediators of arthritic inflammation, namely, edema, arthritic score, presence of immunophenotypes including Foxp3+, CD4+Foxp3+, and CD25+Foxp3+ T regulatory (Treg) cells, as well as pro- and anti-inflammatory mediators. AG126 treatment significantly attenuated the severity of AIA and caused a substantial reduction in the percentage of CD2+, CD3+, CD4+, CD8+, CD23+, CD80+, CD86+ CD122+, CD195+, TCRß+, and GITR+ cells in whole blood. Moreover, administration of AG126 under arthritis-inducing conditions resulted in suppression of IL-17A+, IFN-γ+, CD4+ and CD25+ populations while causing an increase in the Foxp3+, CD4+Foxp3+, and CD25+Foxp3+ Treg populations in the spleen. In addition, RT-PCR analysis revealed increased expression of CD4, CD8, IL-17A, IFN-γ, TNF-α, and NF-κB p65 mRNAs and decreased IL-4 mRNA in the arthritic control (AC) mice, while treatment of animals with AG126 reversed these effects. Western blot analysis confirmed the decreased expression of IL-17, GITR, NF-κB p65 proteins and increased Foxp3 and IL-4 proteins following AG126 treatment of knee tissue. Thus, our findings provide new evidence that inhibition of protein tyrosine kinase activity decreases the progression of arthritis.

Primary well differentiated breast liposarcoma with divergent cartilagenous differentiation: a case report.

Primary liposarcomas of the female and male breasts are very rare. Heterologous differentiation in adipocytic tumors is also an exceedingly rare phenomenon, which is occasionally reported in the literature. We describe the case of a 22 year-old female who presented with a relatively large left breast mass which was clinically diagnosed as a case of giant fibroadenoma, but histologically showed a well differentiated liposarcoma with evidence of extensive chondroid differentiation. The mammographic and radiological features are presented and correlated with the histopathological appearances together with literature review and comparison with similar reported cases.

Tuberculosis of the tongue clinically masquerading as a neoplasm: a case report and literature review.

Tuberculosis of the tongue is a very rare event even in areas and countries in which tuberculosis is endemic. The disease can present itself in a variety of clinical appearances, most of which may mimic malignant lingual neoplasms clinically. In this case, we present a patient who initially complained of an ulcerated lingual swelling, which was suspected to be a squamous cell carcinoma on clinical examination. In addition, the diagnosis was missed on the first and initial biopsy as it was not representative of the lesion. The diagnosis of lingual tuberculosis was made by histopathology on a second biopsy. In this article, we described the clinicopathological features of tuberculous glossitis with a comparison between our case and other similar reported cases in addition to a literature review.

Pseudo-obstruction of the Gastric Outlet Caused by Combined Hyperganglionosis and Ganglioneuromatosis in an adult: Case Report and Literature Review.

Gastrointestinal ganglioneuromatosis is a rare and benign proliferation of both ganglion and Schwann cells, which may present in a variety of clinicopathological characteristics including polypoid, localized and diffuse forms. It is characterized by the presence of a large number of dysplastic ganglion cells or hyperganglionosis. The affected patients are usually children and a number of them have intestinal neuronal dysplasia type B, which may overlap with ganglioneuromatosis. We report a very rare case of gastric ganglioneuromatosis with hyperganglionosis in a 34 year old male, who presented as a case of gastric outlet obstruction and marked gastric dilatation which was diagnosed both clinically and radiologically as a case of gastric obstruction due to gastric malignancy. Based on these findings and because of the patient's deteriorating clinical situation; the patient underwent distal gastrectomy and the final diagnosis was made following the histopathological examination of the resected specimen. The clinicopathological features and diagnostic criteria of this rare disorder are described together with a literature review of other similar cases affecting different parts of the gastrointestinal tract.