Perillyl Alcohol Mitigates Behavioural Changes and Limits Cell Death and Mitochondrial Changes in Unilateral 6-OHDA Lesion Model of Parkinson's Disease Through Alleviation of Oxidative Stress.

In this study, we aim to assess the phytomedicinal potential of perillyl alcohol (PA), a dietary monoterpenoid, in a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease (PD). We observed that PA supplementation alleviated behavioural abnormalities such as loss of coordination, reduced rearing and motor asymmetry in lesioned animals. We also observed that PA-treated animals exhibited reduced oxidative stress, DNA fragmentation and caspase 3 activity indicating alleviation of apoptotic cell death. We found reduced mRNA levels of pro-apoptotic regulator BAX and pro-inflammatory mediators IL18 and TNFα in PA-treated animals. Further, PA treatment successfully increased mRNA and protein levels of Bcl2, mitochondrial biogenesis regulator PGC1α and tyrosine hydroxylase (TH) in lesioned animals. We observed that PA treatment blocked BAX and Drp1 translocation to mitochondria, an event often associated with the inception of apoptosis. Further, 6-OHDA exposure reduced expression of electron transport chain complexes I and IV, thereby disturbing energy metabolism. Conversely, expression levels of both complexes were upregulated with PA treatment in lesioned rats. Finally, we found that protein levels of Nrf2, the transcription factor responsible for antioxidant gene expression, were markedly reduced in cytosolic and nuclear fraction on 6-OHDA exposure, and PA increased expression of Nrf2 in both fractions. We believe that our data hints towards PA having the ability to provide cytoprotection in a hemiparkinsonian rat model through alleviation of motor deficits, oxidative stress, mitochondrial dysfunction and apoptosis.

Megaloblastic anemia: A common but often neglected cause of pyrexia of unknown origin.

OBJECTIVE: The objective was to study megaloblastic anemia as a cause of pyrexia of unknown origin (PUO). MATERIALS AND METHODS: We conducted a study on 15 patients of megaloblastic anemia associated with fever, attending our hospital clinics over a period of 6 months. RESULTS: While 11 patients had symptoms suggesting foci of infection and responded well to intravenous antibiotics, 4 patients had neither any evidence of infection nor responded with empirical broad spectrum antibiotic treatment. They were treated with vitamin B12/folate therapy which led to marked improvement in fever within 48 h. Presenting complaints of the patients and severity/duration of fever along with other epidemiological data were also studied in each case. CONCLUSION: The present study led us to conclude that megaloblastic anemia forms an important and reversible cause of fever and should be ruled out in all patients presenting with PUO. This knowledge would help the physicians in adequate and timely management of these patients.