Exploration of self-medication practice in Pokhara valley of Nepal.

BACKGROUND: Self-medication (SM) is the practice of consuming medication without the consultation of physician. The drugs most commonly self-medicated are paracetamol, analgesics, ranitidine, oral rehydration solution and antibiotics. The objective of the study was to assess the SM status and its causes in Pokhara valley of Nepal. METHOD: The study was conducted among the people residing in Pokhara metropolitan city. The study duration was of 4 months from April to July, 2018. The study population were patients attending health general and oral health screening programs at Baidam, Birauta, Hemja and Pame areas of Pokhara. Structured questionnaire was used to collect demographics of the patients and the details of the usage of self-medication. RESULT: Out of 201 patients, 38.2% patients were found to be self-medicating. The most common illness sought for SM was ache (headache, body ache) in 50% subjects followed by cough and cold in 31% and gastritis in 23%. Paracetamol was the drug consumed by 16 subjects followed by nimesulide by 11. Lack of knowledge about the disadvantages of SM led to self-medication in 65% of respondents. The personnel most commonly consulted for medication were pharmacists (60%). CONCLUSION: The trend of SM is high in Pokhara valley. The comedics were consulted most often for SM due to lack of knowledge of consultation to physicians. The public should be made aware about SM.

Alteration of striatal tetrahydrobiopterin in iron-induced unilateral model of Parkinson's disease.

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin (BH4) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of BH4 into neuron would induce the neuronal toxicity in vitro. To elucidate a role of BH4 in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and BH4 at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and BH4 levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of BH4 was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of BH4 in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both BH4 and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of BH4 can deteriorate the disease progression in early phase of PD, and the inhibition of BH4 increase could be a strategy for PD treatment.

Pharmacokinetics of venlafaxine and its major metabolite o-desmethylvenlafaxine in freely moving mice using automated dosing/sampling system.

OBJECTIVE: To assess the pharmacokinetics of venlafaxine (VEN) and its major metabolite o-desmethylvenlafaxine (ODV) in freely moving mice using automated dosing/infusion (ADI) and automated blood sampling (ABS) systems. In addition, concentration of VEN and its metabolite ODV were also measured in brain by microdialysis. MATERIALS AND METHODS: Venlafaxine was administered directly via jugular vein or gastric catheterization and blood samples were collected through carotid artery. A series of samples with 10 µl of blood was collected from the mouse using ADI/ABS and analyzed with a validated LC-MS/MS system. Extracellular concentrations of VEN and ODV in brain were investigated by using microdialysis procedure. RESULTS: The bioavailability of VEN was 11.6%. The percent AUC ratios of ODV to VEN were 18% and 39% following intravenous and intragastric administration, respectively. The terminal half-life of venlafaxine was about two hours. Extracellular concentration of VEN contributed 3.4% of the blood amount, while ODV was not detected in dialysate. CONCLUSION: This study suggests that besides rapid absorption of VEN, the first-pass metabolism is likely to contribute for its lower bioavailability in the mouse. The proposed automated technique can be used easily to conduct pharmacokinetic studies and is applicable to high-throughput manner in mouse model.

A comparative study of the pharmacokinetics of traditional and automated dosing/blood sampling systems using gabapentin.

OBJECTIVE: The present study was undertaken to investigate the pharmacokinetics (PKs) of gabapentin as determined by traditional manual blood sampling and by using an automated dosing/blood sampling technique in awake and freely moving rats using combined liquid chromatography tandem mass-spectrometry (LC-MS/MS). MATERIALS AND METHODS: PK comparisons were conducted by allocating rats into two groups; an automated dosing/blood sampling (ADI/ABS) group (IV study, n = 6 and intragastric study, n = 6) and a manual group (IV study, n = 6 and oral study, n = 6). A series of blood samples from carotid artery were taken at specified times and analyzed using a validated LC-MS/MS method. Various PK parameters like area under curve (AUC(inf)), maximum concentration, time to reach maximum concentration, terminal half life, distribution volume at the steady state, and total clearance were calculated and the two study groups were compared with respect to these parameters. RESULTS: Significant differences in PK parameters were observed between the manual group and the ADI/ABS group and respective bioavailability were measured (46.82 ± 19.45% and 61.54 ± 21.23%, respectively) which is 1.31-fold difference (P = 0.0051, P<0.05). CONCLUSION: The described ADI/ABS method was found to be a useful drug development tool for accelerating the pace of preclinical in vivo studies and for obtaining reliable and accurate PK parameters even from single animals as it minimized interanimal and physiological variations.

Effect of Ginseng on Calretinin Expression in Mouse Hippocampus Following Exposure to 835 MHz Radiofrequency.

Exponential rise in the use of mobile communication devices has generated health concerns due to radiofrequency (RF) exposure due to its close proximity to the head. Calcium binding proteins like calretinin regulate the levels of calcium (Ca(2+)) which plays an important role in biological systems. Ginseng is known for maintaining equilibrium in the human body and may play a beneficial radioprotectant role against electromagnetic field (EMF) exposure. In the present study, we evaluated the radioprotective effects of red ginseng (RG) extract in a mouse model. Calretinin (CR) expression was measured using a free-floating immunohistochemical method in the hippocampus of mice after 835 MHz EMF exposure for 5 h/d for 5 d at specific absorption rate=1.6 W/kg for the different experimental groups. The control animals were treated with NaCl while the experimental animals received 10 mg/kg ginseng, or 30 mg/kg; EMF exposed mice were also treated with NaCl, 10 mg/kg ginseng (E10), or 30 mg/kg (E30). Decreases in CR immunoreactivity (IR) along with loss of CA1 and CA3 interneurons and infragranular cells were observed in the ENaCl group while such losses were not observed in the E10 and E30 groups. CR IR significantly increased in the RG-treated group compared to control and EMF-exposed groups treated with NaCl. The study demonstrates that RG extract can serve as a radioprotective agent that maintains Ca(2+) homeostasis and prevents neuronal loss in the brain hippocampal region caused by RF exposure.

Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity.

Exponential interindividual handling in wireless communication system has raised possible doubts in the biological aspects of radiofrequency (RF) exposure on human brain owing to its close proximity to the mobile phone. In the nervous system, calcium (Ca(2+)) plays a critical role in releasing neurotransmitters, generating action potential and membrane integrity. Alterations in intracellular Ca(2+) concentration trigger aberrant synaptic action or cause neuronal apoptosis, which may exert an influence on the cellular pathology for learning and memory in the hippocampus. Calcium binding proteins like calbindin D28-K (CB) is responsible for the maintaining and controlling Ca(2+) homeostasis. Therefore, in the present study, we investigated the effect of RF exposure on rat hippocampus at 835 MHz with low energy (specific absorption rate: SAR=1.6 W/kg) for 3 months by using both CB and glial fibrillary acidic protein (GFAP) specific antibodies by immunohistochemical method. Decrease in CB immunoreactivity (IR) was noted in exposed (E1.6) group with loss of interneurons and pyramidal cells in CA1 area and loss of granule cells. Also, an overall increase in GFAP IR was observed in the hippocampus of E1.6. By TUNEL assay, apoptotic cells were detected in the CA1, CA3 areas and dentate gyrus of hippocampus, which reflects that chronic RF exposure may affect the cell viability. In addition, the increase of GFAP IR due to RF exposure could be well suited with the feature of reactive astrocytosis, which is an abnormal increase in the number of astrocytes due to the loss of nearby neurons. Chronic RF exposure to the rat brain suggested that the decrease of CB IR accompanying apoptosis and increase of GFAP IR might be morphological parameters in the hippocampus damages.

Effect of 835 MHz radiofrequency radiation exposure on calcium binding proteins in the hippocampus of the mouse brain.

Worldwide expansion of mobile phones and electromagnetic field (EMF) exposure has raised question of their possible biological effects on the brain and nervous system. Radiofrequency (RF) radiation might alter intracellular signaling pathways through changes in calcium (Ca(2+)) permeability across cell membranes. Changes in the expression of calcium binding proteins (CaBP) like calbindin D28-k (CB) and calretinin (CR) could indicate impaired Ca(2+)homeostasis due to EMF exposure. CB and CR expression were measured with immunohistochemistry in the hippocampus of mice after EMF exposure at 835 MHz for different exposure times and absorption rates, 1 h/day for 5 days at a specific absorption rate (SAR)=1.6 W/kg, 1 h/day for 5 days at SAR=4.0 W/kg, 5 h/day for 1 day at SAR=1.6 W/kg, 5 h/day for 1 day at SAR=4.0 W/kg, daily exposure for 1 month at SAR=1.6 W/kg. Body weights did not change significantly. CB immunoreactivity (IR) displayed moderate staining of cells in the cornu ammonis (CA) areas and prominently stained granule cells. CR IR revealed prominently stained pyramidal cells with dendrites running perpendicularly in the CA area. Exposure for 1 month produced almost complete loss of pyramidal cells in the CA1 area. CaBP differences could cause changes in cellular Ca(2+)levels, which could have deleterious effect on normal hippocampal functions concerned with neuronal connectivity and integration.