Impulse control disorders and related behaviours (ICD-RBs) in Parkinson′s disease patients: Assessment using "Questionnaire for impulsive-compulsive disorders in Parkinson′s disease" (QUIP)

Background: There is limited data on the prevalence of impulse control disorder and related behaviors (ICD-RBs) in Indian patients with Parkinson′s Disease (PD). In the context of potential genetic and environmental factors affecting the expression of ICD-RBs, studying other multiethnic populations may bring in-sights into the mechanisms of these disorders. Objectives: To ascertain point prevalence estimate of ICD-RBs in Indian PD patients, using the validated “Questionnaire for Impulsive-Compulsive Disorders in Parkinson′s disease (QUIP)” and to examine their association with Dopamine replacement therapy (DRT). Materials and Methods: This was a hospital based observational cross-sectional study. After taking informed consent, patients and their informants (spouse, or primary caregiver) were made to complete the QUIP, and were instructed to answer questions based on behaviors that occurred anytime during PD that lasted at least four consecutive weeks. Results: Total of 299 patients participated in the study. At least one ICD-RB was present in 128 (42.8%), at least one Impulse control disorder (ICD) was present in 74 (24.75%) and at least one Impulse control related compulsive behaviour (ICRB) was present in 93 (31.1%) patients. Punding was the most frequent (12.4%) followed by hyper sexuality (11.04%), compulsive hobbyism (9.4%), compulsive shopping (8.4%), compulsive medication use (7.7%), compulsive eating (5.35%), walkabout (4%) and pathological gambling (3.3%). ≥ 2 ICD-RBs were observed in 15.7% of patients. After multivariate analysis, younger age of onset, being unmarried were specifically associated with presence of ICD. Longer disease duration was specifically associated with presence of ICRB. Whereas smoking and higher dopamine levodopa equivalent daily doses (DA LEDD) were associated with both presence of ICD and ICRB. Higher LD LEDD was specifically associated with presence of ICD-RB. Conclusions: Our study revealed a relatively higher frequency of ICD-RBs, probably because of the use of screening instrument and because we combined both ICDs and ICRBs. Also high proportion of DA use (81.6%) among our patients might be responsible. The role of genetic factors that might increase the risk of developing ICD-RBs in this population needs further exploration

Complementary and alternative medicine in Indian Parkinson's disease patients

AbstractUse of complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué) in Parkinson disease (PD) ranged 40–70%. The objective of this study was to determine the frequency, types and factors associated with the use of CAM in Indian PD patients. PD patients, fulfilling UKPD-Society brain-bank diagnostic-criteria, attending Movement-disorders clinic of a tertiary-care teaching hospital in India from 1st May to 15th December 2012 were enrolled. Information on socio-demographic, clinical data and treatment along with factors (source of information, benefits, harms, reason for use and cost) associated with CAM use were recorded. Out of 233 consecutive PD patients, 106 (46%) used CAM. Mean ± SD age of CAM users was 56 ± 11.2 years. Among CAM users, 72% were males, with mean age-onset 49 ± 11.16 years (P = 0.042) and 73% receiving levodopa therapy (p = 0.006). Longer duration PD, higher education (graduates and above), urban residence, and fairly good perceived health were other factors seen among CAM users. Reasons for using CAM were ‘feel good factor’ (73%), 9% took CAM due to side effects from allopathic-medicines. Commonly used CAM were Ayurvedic, homeopathic medicines, and acupuncture (針灸 zhēn jiǔ) [74/106 (70%)]. Median CAM cost in Indian Rupees (INR) was 1000/month (USD16, range: 0-400USD/month in year 2012). Almost half of PD patients use CAM. Three-quarters of Indian CAM using PD patients believe that CAM is harmless, using it at a substantial cost. CAM-users are educated, young, urban dwellers, longer duration PD and receiving levodopa. Commonly used CAM was Ayurvedic, Homeopathic medicines and acupuncture

Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining

Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug

Nuclear localization and in situ DNA damage by Mycobacterium tuberculosis nucleoside-diphosphate kinase

Nucleoside-diphosphate kinase of Mycobacterium tuberculosis (mNdK) is a secretory protein, but the rationale behind secreting an enzyme involved in the maintenance of cellular pool of nucleoside triphosphates is not clearly understood. To elucidate the biological significance of mNdK secretion, we expressed mNdK fused to green fluorescent protein in HeLa and COS-1 cells. Interestingly, mNdK was detected in the nuclei of HeLa and COS-1 cells. Incubation of mNdK with nuclei isolated from HeLa and COS-1 cells led to in situ damage of chromosomal DNA. Surface plasmon resonance studies demonstrated that mNdK binds supercoiled plasmid DNA lacking apurinic/apyrimidinic sites with a dissociation constant of 30 ± 3.2 μm. Plasmid cleavage by mNdK was found to be dependent on the specific divalent metal ion and inhibited by a metal ion chelator. Moreover, the metal ion-dependent DNA cleavage by mNdK was mediated by superoxide radicals as detected by electron paramagnetic resonance. The cleavage reaction was inhibited under nitrogen atmosphere confirming the necessity of molecular oxygen for DNA cleavage. In view of the findings that mNdK is secreted by intracellular mycobacteria and damages the nuclear DNA, it can be postulated that mNdK may cause cell death that could help in the dissemination of the pathogen