Immune checkpoint inhibitors (ICIs) have considerably changed the management of several malignancies. Although these agents transformed the scope of management in oncology and proved long-term efficacy, they have been associated with numerous autoimmune-related adverse events. We presented a case of a 61-year-old male with a history of non-small cell lung cancer (NSCLC) who presented with respiratory failure requiring mechanical ventilation. He was discharged with a working diagnosis of myasthenia gravis crisis secondary to the use of pembrolizumab. On further evaluation, he was found to possibly have pembrolizumab-induced myositis. He was treated with plasmapheresis, methylprednisolone, and rituximab and achieved significant improvement. Pembrolizumab, a monoclonal antibody, is an ICI that targets programmed death protein 1 (PD-1), thereby blocking the interaction between PD-1 and PDL-1, leading to an enhancement of T-cell mediated immune response against tumor cells. Pembrolizumab has been used to treat a variety of malignancies including melanoma, NSCLC, and other solid tumors. Though ICIs have revolutionized the field of oncology, they should be used with caution. ICIs can cause immune-related adverse events (irAEs), including myasthenia gravis and myositis. Diagnosing irAEs is challenging due to their nonspecific presentations and lack of antibody markers. Therefore, patients and clinicians should be aware of irAEs in order to initiate timely intervention.
Despite the frequent clinical use of adult unfractionated bone marrow mononuclear cells (BMMNCs) for cardiac repair, whether these cells are capable of undergoing cardiomyogenic differentiation in vitro remains uncertain. In addition, the role of Wnt signaling in cardiomyogenic differentiation of adult cells is unclear.Unfractionated BMMNCs were isolated from adult mice via Ficoll-Paque density-gradient centrifugation and cultured in the presence of Wnt3a or Wnt11. In control BMMNCs, Wnt11 was not expressed, whereas the expression of markers of pluripotency (Oct-4 and Nanog), as well as that of Wnt3a and beta-catenin, decreased progressively during culture. Exposure to Wnt3a rescued beta-catenin expression and markedly increased the expression of Oct-4 and Nanog, concomitant with increased cell proliferation and CD45 expression. In contrast, exposure to ectopically expressed noncanonical Wnt11 markedly decreased the expression of Oct-4 and Nanog and induced mRNA expression (quantitative real-time reverse-transcription polymerase chain reaction) of cardiac-specific genes (Nkx2.5, GATA-4, atrial natriuretic peptide, alpha- and beta-myosin heavy chain, and cardiac troponin T) by day 3 with subsequent progression to a pattern characteristic of the cardiac fetal gene program. After 21 days, 27.6+/-0.6% and 29.6+/-1.4% of BMMNCs expressed the cardiac-specific antigens cardiac myosin heavy chain and cardiac troponin T, respectively (immunocytochemistry), indicating cardiomyogenic lineage commitment. Wnt11-induced cardiac-specific expression was completely abolished by the protein kinase C inhibitor bisindolylmaleimide I, partially abolished by the c-Jun-N-terminal kinase inhibitor SP600125, and attenuated by the Wnt inhibitor Dickkopf-1.In adult density-gradient separated BMMNCs, canonical Wnt3a promotes stemness, proliferation, and hematopoietic commitment, whereas noncanonical signaling via Wnt11 induces robust cardiomyogenic differentiation in a protein kinase C- and c-Jun-N-terminal kinase-dependent manner.
Bone marrow mesenchymal stem cells (BMMSCs) are typically isolated as adherent cells; the importance of antigen expression on cardiomyogenic potential of (BMMSCs) remains unclear. Although BMMSCs d...
We prospectively evaluated the role of the oral proteolytic enzyme, Phlogenzym®, in hastening recovery from extravasation due to vinka alkaloid and/or anthracycline chemotherapy Patients with definitive extravasation due to vesicant chemotherapy were enrolled in the study Baseline characteristics were documented and the patients were started on one tablet of Phlogenzym® three times daily for a total of 1 month. Effects on swelling, pain, tenderness, redness, discoloration, ulceration and the patients' outcome were recorded. Patients whose features worsened were considered treatment failures and underwent plastic surgery Adverse effects were evaluated according to the World Health Organization's toxicity criteria. Of the 15 patients enrolled, one remains in the study and 14 are evaluable for efficacy Complete resolution was found in 10, partial response in two and progressive disease requiring reconstructive surgery in the remaining two. All responders recovered in a median of 13 days. In two patients, chemotherapy was delayed for 15 and 18 days, respectively. Toxicity of Phlogenzym® was mild and self-limiting. Phlogenzym® is safe and effective in recovery from vesicant chemotherapy extravasation and is useful even in patients with delayed presentation. The drug is easy to administer, cost effective and readily acceptable to patients. Twelve of the 14 patients showed no adverse effects while on the chemotherapy schedule.
Abstract Background Many pesticides contain fluoride that enters the food chain and affect the non-target organisms. Fluoride is a known neurotoxin and may cause neurobehavioral defects. A study was conducted to see the effect of fluoride on the learning and memory ability of larvae of Zaprionus indianus . The learning and memory ability of 2nd instar larvae of normal (control) and sodium fluoride (NaF)-treated Zaprionus indianus was compared . Results Sublethal concentration of NaF for Z . indianus was found to be 0.8 ppm. Olfactory assay results showed that the larvae of normal (control) Z . indianus had better learning and memory ability in comparison to NaF-treated larvae. Conclusions This study indicates that the insects exposed to pesticides containing fluoride may have difficulty in locating food sources and carrying out pollination.
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