Carbamazepine verses valproic acid as monotherapy in epileptic patients

Objective: To evaluate the effectiveness of carbamazepine and valproic acid as monotherapy in epileptic patients of Pakhtun population. Study Design: An experimental study. Place and Duration of Study: The outpatient Neurology Department, Lady Reading Hospital, Peshawar, from August 2014 to April 2016

Methodology: Epileptic patients placed on carbamazepine and volproic acid were inducted. Carbamazepine and valproic acid plasma levels were determined using reverse phase high performance liquid chromatography. Plasma levels of vitamin B6 and homocysteine were determined at baseline before the switching to carbamazepine and valproic acid therapy, and on the sixth month of the therapy. Hemoglobin [Hb] level were also determined through blood analyser. Clinical response [number of seizures per week] was evaluated on third and sixth month of the therapy

Results: There were 79 patients in carbamazepine group and 82 in the valproic acid group. Mean age of patients was 18.08 +/-8.6 years in carbamazepine group and 17.5 +/-7.04 years in the valproic acid group. Median dose of carbamazepine was 400 mg/day at baseline and at 6[th] month of therapy. Median dose of valproic acid was 500 mg/day and 750 mg/day of valproic acid at baseline and end study point. Difference in homocysteine, vitamin B6 and Hb levels were statistically significant [p<0.05] in carbamazepine cohort compared to valproic acid cohort. The frequency of seizures in the carbamazepine was 0.85 times more compared to valproic acid at the end study point

Conclusion: Hyperhomocysteinaemia and lower vitamin B6 and Hb levels was found in the carbamazepine cohort. The frequency of number of seizures/week was higher in the carbamazepine cohort compared to valproic acid cohort

Isolation of flavonoides from Artemisia macrocephala anticholinesterase activity: isolation, characterization and its in vitro anticholinesterse activity supported by molecular docking

In this study the flavonoids isolated from Artemisia macrocephala were screened out for anticholinesterase activity. The isolated flvanoids were characterized by HNMR, NOESY, COSY, HMBC, HSQC and mass spectroscopy. The compounds [1-4] in appropriate quantities were isolated from chloroform fraction using gravity column chromatography by eluting ethyl acetate/n-hexane solvent system. The flavonoids were characterized and resulted in the form of mono substituted methoxy flavones to tri substituted flavones. Ellman's assay techniques were used to find out enzyme inhibition. Operating environment [MOE] software was used for molecular docking studies. Compounds [1], [2] and [3] showed 88.42+/-2.76, 84.50+/-1.60 and 90.16+/-2.98 percent inhibition of the acetyl cholinesterase [AChE] respectively at 1000µg/mL concentrations with IC50 value 165, 60, 65µg/mL respectively which were comparable to that of standard galanthamine. While for butyryl cholinesterase [BChE], [1], [2] and [3] showed 91.63+/-4.32, 81.03+/-3.53 and 87.69+/-2.84 percent inhibitions respectively at 1mg/mL as compared to the standard galanthamine which caused 96.50+/-2.41 percent inhibition at the same concentration. Whereas, compound [4] exhibited moderate activity for both the enzymes. Molecular docking studies confirmed the experimental AChE and BChE inhibitory activities of the test samples by their virtue of multiple interactions with target enzymes. The results confirm that the specie has biologically active constituents that are more useful for the management of several neurodegenerative ailments like ataxia, Parkinson's disease, Alzeimer's disease and some other types of dementia

Parasiticidal and brine shrimp cytotoxicity potential of crude methanolic extract of rind of Punica granatum Linn against round worms and tape worms

Rind of Punica granatum is traditionally used for anthelmintic purposes. The current work describes the possible anthelmintic activity of crude methanolic extract of Punica granatum [Pg. Cr] against round worms [Ascaridia galli] and the tape worms [Raillietina spiralis]. Brine shrimp cytotoxicity is also performed. Brine shrimp cytotoxic activity was tested using different concentrations [1000µg/ml, 100µg/ml and 10µg/ml] of Pg.Cr. In vitro anthelmintic activity of Pg. Cr was determined against the parasites using albendazole and piperazine citrate as st and ard anthelmintic drugs in concentration 10 mg/ml. LC50 value for Brine shrimp cytotoxicity was 189.44+/-28µg/ml. In test concentration of 40mg/ml of the Pg. Cr, Raillietina spiralis was paralyzed in 23 minutes. However, for parasiticidal activity [death of the parasite], it took less time [40 minutes] as compared to st and ard Albendazole. Time taken for death of the parasite Raillietina spiralis, in concentration 40 mg /ml, is 40 min. While st and ard drugs took more time to kill the Raillietina spiralis. Pg. Cr took 19 minutes to paralyze the Ascaridia galli at concentration 40 mg/ml whereas; it took 48 minutes for to kill the parasite Ascaridia galli. The current work confirms the traditional use of rind of Punica granatum as anthelmintic against Raillietina spiralis and Ascaridia galli. Results of brine shrimp cytotoxicity assay warrant for the isolation of cytotoxic compounds. List of abbreviation: Pg. Cr = Crude methanolic extract of Punica granatum

Acute toxicity and antispasmodic activities of achillea wilhelmsii C. Koch

Since Achillea wilhelmsii is used as antispasmodic in traditional medicine, we conducted our current work to investigate its rationale on scientific grounds. Acute toxicity studies of crude methanol extract of Achillea wilhelmsii [Aw. CMeOH] is also performed. Effect of Aw. CMeOH and its fractions were tested on isolated sections of rabbits' jejunum at test concentrations 0.01, 0.03, 1.0, 3.0, 5.0 and 10mg/ml. The test extracts, in similar concentrations, were also tested on KCl-induced contractions. Calcium chloride curves were constructed for those fractions which relaxed KCl induced contractions in the absence and presence of the test samples to investigate its possible mode of action through calcium channels. Aw. CMeOH tested positive for flavonoids, saponins, tannins, glycosides, terpenoids, sterols, phenols, carbohydrates and proteins. LD[50] for acute toxicity studies is 2707 +/- 12.6 mg/kg. Mean EC[50] values for Aw. CMeOH on spontaneous and KCl-induced contractions are 3.41 +/- 0.18 [2.56-3.8, n=6] and 0.68 +/- 0.05 [0.6-0.85, n=6] mg/ml, respectively. Respective EC[50] values for n-hexane fraction on spontaneous and KCl-induced contractions are 3.06 +/- 0.08 [2.8-3.3, n=6] and 1.68 +/- 0.8 [1.4-1.9, n=6] mg/ml, respectively. Corresponding EC[50] [mg/ml] values for chloroformic, ethylacetate and aqueous fractions of Achillea wilhelmsii on spontaneous rabbits' jejunum preparations are 4.8 +/- 0.2 [4.41-5.63, n=6], 5.07 +/- 0.15 [4.7-5.58, n=6] and 5.2 +/- 0.13 [4.91-5.64, n=4], respectively. Constructing calcium chloride curves, in the presence of 0.1 mg/ml of Aw. CMeOH, mean EC[50] value [log molar [Ca[++]]] is-1.98 +/- 0.03 [-1.89-2.05, n=6] vs. control EC50 [log molar [Ca[++]]]-2.41 +/- 0.02 [-2.32-2.44, n=6]. Mean EC50 value [log molar [Ca[++]]] for 0.3 mg/ml n-hexane fraction is-1.76 +/- 0.05 [-1.70 -1.93, n=6] vs. control EC50 [log molar [Ca[++]]] value-2.18 +/- 0.07 [-2.0-2.46, n=6]. While in the presence of chloroformic fraction [3 mg/ml], mean EC50 [log molar [Ca[++]]] value is -2.4 +/- 0.1 [-2.78 - 2.9, n=6] vs. control EC50 [log molar [Ca[++]]] value-2.70 +/- 0.05 [-2.5-2.8, n=6]. Mean EC50 value [log molar [Ca[++]]] for ethyl acetate fraction [1 mg/ml] is-1.94 +/- 0.07 [-1.75-2.05, n=6] vs. control EC50 [log molar [Ca[++]]] value-2.69 +/- 0.04 [-2.57-2.79, n=6]. Mean EC50 [log molar [Ca[++]]] value for residual aqueous fraction [3 mg/ml] is-1.8 +/- 0.3 [-1.71-1.84, n=6] vs. control EC50 [log molar [Ca++]] -2.6 +/- 0.04 [-2.59-2.76, n=6]. Whereas, the verapamil [0.1 micro M] EC[50] value [log molar [Ca[++]]] is-1.7 +/- 0.1 [-1.6-1.8, n=6] vs. control EC50 value [log molar [Ca[++]]]- 2.4 +/- 0.09 [-2.3-2.47, n=6]. The present research work confirms that the intestinal relaxation effect of Achillea wilhelmsii is supporting its traditional use as antispasmodic. The plant species can be a source for calcium antagonist[s], which can preferably be isolated from n-hexane fraction

Evaluation of patients with coronary artery disease for major modifiable risk factors for ischemic heart disease

Incidence of cardiovascular diseases is on the rise in developing countries. Deaths due to ischemic heart disease can be reduced by modifying the risk factors. The present study was conducted to evaluate the patients scheduled for Coronary Artery Bypass Surgery for the presence of major modifiable risk factors for ischemic heart disease [IHD]. It was a descriptive study. All patients who underwent elective Coronary Artery Bypass cardiac surgery between November 1, 2008 and February 28, 2009 at Rehman Medical Institute, Peshawar, were included in the study. Presence of Diabetes, Hypertension, Smoking, Dyslipidemia, Sedentary life style, and Obesity was looked for in these patients. A total of 104 patients were studied during this period. Majority [97.11%] of patients had at least one major modifiable risk factor for IHD. Sedentary life style [53.84%] was the most common risk factor present in these patients followed by hypertension and dyslipidemia [47.11% each], smoking [43.27%], diabetes [35.57%], and obesity [9.61%]. Multiple risk factors [two or more] were found in 78 [75.0%] of patients. Most of the patients with coronary artery disease, severe enough to warrant coronary artery bypass grafting, have at least one of the major modifiable risk factors for IHD. Modification of these factors may well reduce the disease burden of CAD and reduce the cardiovascular mortality.

antifungal, cytotoxic, antitermite and insecticidal activities of zizyphus jujube

Plants are very useful, self-generating machines, producing a variety of useful bioactive products. Keeping in view this idea, the crude methanolic extract and various fractions of Zizyphus jujuba were screened for antifungal, cytotoxic, antitermite and insecticidal activities. Low activity was shown by the crude methanolic extract [12%], n-hexane [9%], chloroform [20%] and ethyl acetate [14%] fraction against Penicillium notatum. Low activity was shown by the ft-hexane fraction against Aspergillus niger [10%] and Trichoderma harzianum [13%] and inactive against Aspergillus flavus, Fusarium oxysporum and Rhizopus stolonifer. The CHC1[3] fraction exhibited low activity of 10% against F. oxysporum while showing no activity against the rest of the test fungi. All the test samples were inactive against Rhizopus stolonifer. The crude methanolic extract was highly cytotoxic [73.33%] at the concentration of 1000 [microg/ml] while the rest of the test samples were low in toxicity at the same concentration. The crude methanolic extract of Zizyphus jujuba showed significant antitermite activity against Heterotermes indicola, among the test samples. Against Tribolium castaneum, Rhizopertha dominica and Callosbruchus analis the insecticidal activity was determined. All the test samples except rc-hexane showed low activity [20%] against T. castaneum. The w-hexane fraction showed low activity [20%] against R. dominica while the rest of the fractions were inactive against it. Low activity of 40% and 20% was shown by the chloroform and "-hexane fraction respectively against C. analis. The results of the present study revealed that the plant could be as potent source of cytotoxic drugs

Spasmogenic and spasmolytic activities Onosma griffithii Vatke

Methanolic extract of Onosma grifflthii and its fractions were evaluated for possible effects on rabbits' jejunum preparations. Rabbits of either sex [weight 1.5-2.0 kg] were used in experiments. Studies were carried out on rabbits' jejunum preparations. Crude methanolic extract of Onosma griffithii [Meth.OG] was tried in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on rabbits' jejunum preparations. Meth.OG was also tried on KCl-induced contractions to explain its possible mode of actions in the presence and absence of atropine [0.03 microM]. Fractions of Meth.OG were tried in similar manner. Calcium chloride curves were constructed for Meth.OG treated tissues that were compared with curves constructed for verapamil in same fashion. Preliminary phytochemical screening of the plant was also performed. Meth.OG increased the amplitude of spontaneous activity of rabbits' jejunum preparations at concentrations of 0.1, 0.3 and 1.0 mg/ml. However, spasmolytic effects were observed at higher concentrations 3.0, 5.0 and 10.0 mg/ml. Mean EC[50] values [mg/ml], respectively, in absence and presence of atropine were 7.5 +/- 0.25 [6.9-8.4, n=6] and 3.0 +/- 0.17 [2.3-3.5, n=6, P<0.05]. Mean EC[50] values, respectively, for effects on spontaneous and KCl-induced contractions were 7.5 +/- 0.25 [6.9-8.4, n=6] and 7.3 +/- 0.35 [6.25-8.2, n=6, p<0.05]. rc-Hexane, chloroform and ethyl acetate fractions showed their respective EC[50] values [mg/ml] 9.7 +/- 0.25 [8.6-10.2, n=6], 4.0 +/- 0.2 [3.5-4.6, n=6] and 1.07 +/- 0.093 [0.78-1.5, n=6]. EC[50] values for calcium chloride curves in presence of 0.3 mg/ml Meth.OG were - 2.27 +/- 0.038 [- 2.4 to - 2.10, n=6] vs. control - 2.78 +/- 0.04 [-2.9 to - 2.6, n=6,P<0.05] Log [Ca[++]]M. Comparing with curves of calcium chloride constructed in presence of 0.1 juM verapamil, the EC[50] [log [Ca[++]] M] values were - 1.82 +/- 0.087 [- 2.0 to - 1.65, n=6] vs. control - 2.64 +/- 0.089 [- 2.9 to - 2.4, n=6] demonstrated a right shift [p<0.05]. Meth.OG tested positive for terpenes, saponins, sterols, flavonoids and carbohydrates. We concluded that the relaxant effect of Meth.OG is exerted through blocking of calcium channels. However,

butanolic and aqueous fractions produced spasmogenic effects that require further work for isolation of pharmacologically active substances