In silico study of thymohydroquinone interaction with blood-brain barrier disrupting proteins.

AIM: To evaluate the inhibitory interaction of thymohydroquinone against blood-brain barrier (BBB)-associated neuropsychiatric and neurodegenerative disorders. MATERIALS & METHODS: An elaborated in silico study was designed to evaluate the interaction of thymohydroquinone with BBB-disrupting proteins and to highlight its pharmacokinetic and safety attributes. RESULTS: Thymohydroquinone demonstrated stable interaction with BBB-disrupting protein active site with Ki (inhibition constant) ranges of (2.71 mM-736.15 µM), binding energy (-4.3 to 5.6 Kcal/mol), ligand efficiency (-0.36 to 0.42 Kcal/mol) and root mean square deviation value of (0.80-2.59 Å). CONCLUSION: Further pharmacokinetic analysis revealed that thymohydroquinone is BBB and central nervous system (CNS) permeant with high acute toxicity and could be a candidate drug for the treatment of these neurological conditions.

Current Progress of Phytomedicine in Glioblastoma Therapy.

Glioblastoma multiforme, an intrusive brain cancer, has the lowest survival rate of all brain cancers. The chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling pathways. These complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy resistance. Therefore, the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound importance. Medicinal plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers, modulate anti-cancer pathways and immunological responses to facilitate their eradication, and induce apoptosis. These phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis, chemotherapy resistance and angiogenesis. These plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and recurrence. In this review, we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics, and also highlighted their mode of action and pharmacological profile.

Short Communication: Evaluation of antimicrobial activities of Harmine, Harmaline, Nicotine and their complexes.

Harmine, Harmaline, Nicotine and its various complexes synthesized have been characterized by physical, spectral and analytical methods and curtained for in-vitro antimicrobial activity against different bacterial and fungal species at two different concentrations i.e.100µ/100µl and 200µ/100µl dose level respectively. Analysis showed that Nicotine, Zinc-Nico, Cd-Nico, Hg-Nico, Ni-Nico, Cu-Nico, Co-Nico, Harmine, and Harmaline having conc. of 100ug/ 100ul had antibacterial activity on zero, 5, 4, 10, zero, 5, 7, zero, zero strain of bacteria having an average of zero (SD=0.0000), 15.2000 (SD=1.30384), 18.2500 (SD=3.30404), 20.2000 (SD=1.39841), zero (SD=0.0000), 14.6000 (SD=0.89443), 15.8571 (SD=1.34519), zero (SD=0.0000), zero (SD=0.0000) respectively. Zinc (II) chloride, Cadmium (II) Iodide, Mercury (II) chloride, Nickel (II) chloride, Copper (II) chloride, Cobalt (II) chloride, Mercury (II) chloride, Mercury (II) harmine, Mercury (II) harmaline at 100ug/100ul is valid for 7, 8, 9, 2, 7, 8, 9, 10, 8 strains of bacteria with an average of 7.1429 (SD=1.06904), 10.0000 (SD=5.01427), 14.8889 (SD=6.00925), 6.0000 (SD=0.0000), 8.5714 (SD=4.27618), 8.2500 (SD=0.88641), 14.8889 (SD=6.00925), 18.6000 (SD=2.45855), 18.5000 (SD=1.85164) respectively. The above given compounds at the conc. of 200 µ/100ul is valid for 10, 9, 10, 8, 8, 10, 10, 10, 10 strains of bacteria with an average of 8.1 (SD=1.66333), 11.7778 (SD=5.28625), 16.1000 (SD=6.36745), 6.5000 (SD=0.92582), 9.7500 (SD=4.43203), 9.9000 (SD=2.76687), 16.1000 (SD=6.36745), 22.0000 (SD=2.44949), 20.4000 (SD=2.75681) respectively. The above given compounds at conc. of 200 µ/100ul showed antibacterial action on 3, 8, 8, 10, 3, 9, 8, zero, 3 strains of bacteria with an average of 14(SD=0.000), 16.8750 (SD=1.35620), 18.2500 (SD=3.45378), 22.7000 (SD=1.82878), 14.3333 (SD=0.57735), 16.7778 (SD=1.71594), zero (SD=0.000), 12.0000 (SD=1.00000) respectively. Hence according to the average value of the zone of inhibition, maximum antibacterial activity at 100-200ug/100ul is of Hg-Nico and Mercury salt; Mercury (II) harmine having an average of 20.2000 (SD=1.39841)-22.7000 (SD=1.82878) and 18.6000 (SD=2.45855)-22.0000 (SD=2.44949). Minimum antibacterial activity at 100-200ug/100ul is Nicotine100, Nicotine-Nico100, Harmine 100,Harmaline 100, Harmine 200 having zero average (SD=0.000).

Knowledge, attitudes and perceptions towards polio immunization among residents of two highly affected regions of Pakistan.

BACKGROUND: Despite the efforts of national and international organizations, polio has not been eradicated from Pakistan. The prevalence of polio in Pakistan is exceptional in global context. Quetta and Peshawar divisions are amongst the most affected regions hit by polio in Pakistan. This study was carried out to assess the knowledge, attitudes and perceptions towards polio immunization among residents of Quetta and Peshawar divisions in Pakistan. METHODS: A descriptive, cross-sectional study involving 768 participants was conducted from August to December, 2014 in Quetta and Peshawar divisions in Pakistan. Multistage sampling technique was used to draw a sample of residents from each division. A pre-tested, self-administered questionnaire was used to collect the data from eligible participants. Descriptive and logistic regression analyses were used to express the results. RESULTS: A total of 38.8 % participants exhibited good knowledge about polio. Mean knowledge score of the participants was 7.35 ± 2.54 (based on 15 knowledge questions). Older age (p < 0.001), low qualification (p < 0.05), rural locality (p < 0.05) and Quetta division (p < 0.001) were significantly associated with poor knowledge of polio. A large proportion of participants displayed negative attitudes towards polio immunization (84.8 %), with a mean score of 19.19 ± 2.39 (based on 8 attitude statements). Lack of education (p < 0.001) and rural residence (p < 0.001) were significantly associated with the negative attitudes of participants towards polio immunization. False religious beliefs (39.06 %), lack of knowledge (33.7 %), fear of infertility by polio vaccines (32.16 %) and security issues (29.42 %) were reported by the participants as the main barriers towards polio immunization. CONCLUSION: The findings of this study showed poor knowledge and negative attitudes of participants towards polio immunizations. Religious beliefs and lack of knowledge about polio immunization were reported as the major barriers towards polio immunization.

Predictive Factors of Suicide Attempt and Non-Suicidal Self-Harm in Emergency Department.

INTRODUCTION: Suicide is the third cause of mortality in America, second leading cause of death in developed countries, and one of the major health problems. Self-harm is self-inflicted damage to one's self with or without suicidal intent. In the present study, the predictive factors of suicide attempt and non-suicidal self-harm were evaluated in patients referred to emergency department (ED) with these problem. METHODS: The total number of 45 patients with suicide attempt or self-harm admitted to ED were included. Clinical symptoms, thoughts and behaviors of suicidal, and non-suicidal self-harm in these patients were evaluated at baseline. Suicidality, suicidal intent and ideation, non-suicidal self-injury, social withdrawal, disruptive behavior, and poor family functions were evaluated at admission time. Brief clinical visits were scheduled for the twelfth weeks. In the twelfth week, patients returned for their final visit to determine their maintenance treatment. Finally, data were analyzed using chi-squared and multiple logistic regression. RESULTS: Forty-five patients were included in the study (56.1% female). The mean age of patients was 23.3±10.2 years (range: 15-75; 33.3% married). Significant association of suicide and self-injury was presented at the baseline and in the month before attempting (p=0.001). The most important predictive factors of suicide and self-harm based on univariate analysis were depression (suicidal and non-suicidal items of Hamilton depression rating scale), anxiety, hopelessness, younger age, history of non-suicidal self-harm and female gender (p<0.05). The participants' quality of life analysis showed a significant higher quality in physical component summary (p=0.002), mental component summary (p=0.001), and general health (p=0.001) at follow up period. CONCLUSION: At the time of admission in ED, suicide attempt and non-suicidal self-harm are subsequent clinical markers for the patient attempting suicide again. The most independent predictive factors of suicide attempt and self-harm were poor family function, hopelessness, non-suicidality items of Hamilton depression rating scale, history of non-suicidal self-harm, and anxiety disorders.