Progressive multifocal leukoencephalopathy in an immunocompetent patient: A case report and review of literature.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, caused by the John Cunningham virus (JCV) is usually seen in patients who are immunocompromised. Here, we describe a case of an immunocompetent patient diagnosed with PML and a comprehensive literature review. A 64-year-old Caucasian male presented with acute worsening of progressive neurological decline with difficulty in vision and reading. Based on history, examination, cerebrospinal fluid markers, histopathology, and magnetic resonance imaging brain at the time of presentation diagnosed the patient with PML in a setting of no immunosuppression disorder. The patient was started on Pelfilgrastim with significant systematic improvement. In our literature review, it was seen that the average age of symptom presentation was 57.5 with predominance in males. Most of the patients presented with progressive neurological deficits with symptomology ranging from mild confusion, aphasia, anxiety to sensory disturbances with numbness, hemiparesis, and hemianopsia. Out of the 21 cases, patients responded to mirtazapine and intravenous pulse methylprednisolone (IVMP). The mortality rate was close to 50% with 11 fatal cases and 10 nonfatal cases. Our case and literature review demonstrate the possibility that PML may very rarely occur in patients that are immunocompetent. Furthermore, our review showed that patients responded well to mirtazapine and IVMP. We also want to highlight that the mortality rate was lower in this review and was only compared to mortality in PML associated with immunocompromised status.

Molecular Mechanisms Responsible for In Vitro Cytotoxic Attributes of Conyza bonariensis Extract against Lymphoblastic Leukaemia Jurkat Cells.

BACKGROUND: Conyza bonariensis is known to have anti-cancer properties. OBJECTIVE: The current study investigated the in vitro pro-apoptotic properties of Conyza bonariensis (C. bonariensis) towards human lymphoblastic leukemia Jurkat cells. METHODS: Ariel parts of C. bonariensis were macerated in a non-polar (n-Hexane) solvent. MTS cell viability assay was employed to determine the cytotoxic activity of the extract towards human leukemia Jurket cells and normal Peripheral Blood Mononuclear Cells (PBMCs). The phytochemical composition of the extract was screened using HPLC method. Flow cytometric studies (FACS) were conducted to explore the pro-apoptotic potential of the extract. Western blot studies were employed to identify the molecular targets involved in the induction of apoptosis. RESULTS: The n-hexane extract showed selective cytotoxic activity towards Jurkat cells. FACS analysis indicated that the extract induced early and late apoptosis in Jurkat cells. Western blot studies revealed that the extract downregulated the expression of DNMT1, SIRT1, and UHRF1 with a simultaneous up-regulation of p73 and caspases-3 proteins expression. HPLC characterization of the extract revealed the presence of phenolic compounds. CONCLUSION: Overall, these findings demonstrate that the anti-cancer effects of a Conyza bonariensis extract towards human lymphoblastic leukemia Jurkat cells are due to the modulation of the activity of multiple oncogenic and tumor suppressor proteins. Phenolic contents of the extract are proposed to be responsible for these activities.