African Journal of Pharmacy and Pharmacology

Published by Academic Journals
Online ISSN: 1996-0816
Publications
Article
Activated charcoal (AC) has been utilized in the absorption of toxins from the intestinal tract of animals as well as humans. Some studies however have implied microbial adsorption at the interstices of AC surface. Activated charcoal has also been suggested and used as a treatment option for diarrhea. Metronidazole, a nitroimidazole derivative has been successfully utilized in the treatment of Clostridium difficile-associated diarrhea (CDAD) as well as anaerobic infections. It has little or no activity against Escherichia coli 0157:H7. The purpose of this study is to compare the activity of metronidazole-AC combination to that of AC alone in the management of E. coli 0157: H7. Utilizing an in vitro pharmacodynamic model in triplicate, E. coli 0157:H7 was exposed to peak concentrate of 32 mg/L of metronidazole daily. Time kill curve was analyzed for time to 3 log killing slope and re-growth of the micro-organism. Minimal inhibitory concentrations (MICs) for pre-exposure to metronidazole were 1 mg /L. Metronidazole alone did not decrease the starting inoculums of E. coli 0157:H7. However, the metronidazole - AC combination achieved a 2 - log killing against E. coli 0157:H7 as well as a significant reduction in the starting inoculums below the lower limit of bacterial counting accuracy (LLA) when AC alone was used. The metronidazole -AC MIC for E.coli increased 5 fold when compared to utilization of AC alone or metronidazole alone. Metronidazole -AC will be useful in the treatment of mild to moderate diarrhea associated with E.coli 0157:H7.
 
Article
In the present study, a new series of compounds (3 to 22) containing pyrazole moiety clubbed with 1,2diazanaphthalene ring, structurally related to celecoxib and naproxen was synthesized. The compounds were evaluated for anti-inflammatory activity using carrageenan induced rat paw edema bioassay. Compounds showing marked anti-inflammatory activity were further tested for their analgesic, ulcerogenic and lipid peroxidation effect using naproxen as reference drug. The results showed that compounds 6, 13 and 14 exhibited good anti-inflammatory and analgesic activity with minimum gastric irritation. Compounds 13 and 14 emerged as potent anti-inflammatory (with percentage inhibition of 79.23 and 76) and analgesic agent (with percentage protection of 68.72 and 67.68) in the present study.
 
Article
A series of 2,5-dimercapto-1,3,4-thiadiazole derivatives (compounds 1 to 10) were prepared by nucleophilic substitution reaction between 2,5-dimercapto-1,3,4-thiadiazole and chloroheterocyclic compounds in methanol and in the presence of potassium carbonate (compounds 1 to 5 and 8) or metallic sodium (compounds 6, 7, 9 and 10) at room temperature. The cytotoxic activity was determined by green fluorescent protein (GFP)-based assay and anti-candida activity was determined by resazurin microplate assay (REMA). Compounds 1 to 4, 8 and 9 showed in vitro cytotoxic activities against Vero cells (African green monkey kidney). Compounds 4 and 10 exhibited anti-candida activities against Candida albicans (ATCC 90028) with IC50 values of 1.94 and 19.10 μg/ml, respectively. Docking studies on the catalytic site of cytochrome P450 14α-demethylase were used to identify the chemical structures in the molecule responsible for cytotoxic and anti-candida activities of the synthesized compounds.
 
Article
We have examined the potential antinociceptive effects of some piperidine derivatives (6a-f), using tail flick method in mice. Morphine was used as positive control drug. The results showed that compound 6b, having a bromine atom at 4 position, was the most active agent tested. The activity of this compound at 50 mg/kg was comparable to morphine (3 mg/kg). Based on the similarities between our compounds and meperidine like structures such as fentanyl, a group of mice was treated with naloxone before administration of 6f. It was concluded that opioid receptors could be the dominant mechanism for the antinociceptive activity of these types of structures. Electrostatic map, distance analysis and superimposition between fentanyl and compound 6b were also studied.
 
Article
Momordica anti-HIV protein of 30 kDa (MAP30) was found to have anti-tumor activities. Therefore, in the present study the effects of MAP30 on the proliferation and apoptosis of human esophageal carcinoma EC-1.71 cells were investigated. The antiproliferative activities were determined using methyl thiazolyl tetrazolium (MTT) assay, colony formation and tumor xenograft model of nude mice. Morphological changes were observed by microscopy. The normal, apoptotic and necrotic cells were identified by fluorescence staining. The percentage of apoptosis and the proportion of the periodic cells were displayed by flow cytometry analysis. The level of mitochondria membrane potential (ΔΨm) was determined by 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) fluorescent probe assay and the content of cytochrome C (Cyt C) was investigated by enzyme-linked immunosorbent assay (ELISA). The activity of Caspase-12 was investigated by Caspase-12 Fluorometric Assay. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression was investigated by immunocytochemical staining. Our results indicated that MAP30 could suppress the cells proliferation, induce the cells apoptosis, decrease the proportion of cells in S phase, and increase the proportion of cells in G0/G1 phases. Treated with MAP30, the ΔΨm decreased, the Cyt C content and the Caspase-12 activity increased, and the NF-κB protein translocated. In conclusion, the recombinant MAP30 could suppress the esophagus carcinoma 1.71 (EC-1.71) cells proliferation and induce their apoptosis.
 
Article
To analyze the reports of adverse reactions caused by amoxicillin and explore its occurrence rules and characteristics. To collect the cases of adverse reactions caused by amoxicillin in the past five years in the hospital and make the statistical analysis. In the reports of the 102 cases of adverse reactions, the clinical manifestations were mainly skin and its accessory damage and systemic damage. Allergic reaction is the most common clinical manifestation of the adverse reactions caused by amoxicillin, and physicians should pay attention to patient's history of drug allergy and make close observation at the first drug use, which has important significance in prevention of the adverse reactions caused by amoxicillin.
 
Article
This study was aimed at evaluating the immune boosting potential of crude methanolic extract of Moringa oleifera in chickens experimentally challenged with Newcatle disease (ND) virus.One hundred and twenty forty two (42) day old chicks were randomly divided into four equal groups. Groups I and II were given daily oral treatment of methanolic extract of M. oleifera at 200 mg/kg body weight until day 56 of age. Groups II and III were vaccinated with the La Sota strain of ND vaccine. Group I was not vaccinated while group IV was left as untreated/unvaccinated control. All the groups were challenged with the velogenic strain of ND virus (VNDV) on day 56. Following challenge, the birds were assessed for cellular and humoral immune responses. Data on cellular and humoral immune responses were analysed using the statistical package for social sciences (SPSS). Increases in total and differential cell numbers and haemagglutination inhibition (HI) titre in the extract-treated groups did not correlate with total protection against ND. M. oleifera extract increased ND HI titre and the total and differential leukocyte counts in the treated and unvaccinated group I birds much more than those of treated and vaccinated group II birds, hence it could be recommended as a prophylactic treatment against ND in non vaccinated birds. Key words: Velogenic Newcastle disease, chickens, Moringa oleifera, immunity.
 
Article
To investigate the expression and its significance of interleutin-17 (IL-17) and immunoglobulin E (IgE) in patients with bronchial asthma, sixty adult patients with bronchial asthma and 30 healthy human control were sequentially enrolled in this study. The production of IL-17 was measured by enzyme-linked immunosorbent assay (ELISA) and fluorescent quantitative polymerase chain reaction (qPCR), respectively. The correlation between expression of IgE and IL-17 was analyzed. It was found that IL-17 was significantly up-regulated in bronchial asthma in comparison to the health control on mRNA level, and serum levels of IL-17 and IgE in bronchial asthma were significantly higher than those in health control, respectively (P < 0. 001). Significant positive correlation in bronchial asthma were found between expression of IL-17 and IgE (r = 0.7082, P = 0.0418). The present study implied that expressions of IL-17 and IgE play an important role in the development of bronchial asthma. Key words: Bronchial asthma, immunoglobulin E, interleukin-17, enzyme-linked immunosorbent assay (ELISA).
 
Article
The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in the IL-18 promoter gene, which regulates IL-18 gene expression in the patients with lichen planus (LP) in Chinese. Two SNPs of the IL-18 promoter gene at positions -607C/A and -173G/C were analyzed in 79 patients with LP and 85 controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between IL-18 variants and LP risk were estimated by computing the ORs and 95% CIs from logistic regression analyses. There was a significant difference in IL-18-607 genotype distributions between the patient and the control groups (P = 0.03). The distribution of IL-18-137G/C genotype was not significantly different between LP and controls (P = 0.66). The identified polymorphisms at the IL-18 promoter region were likely to exert positive effect on the protection of LP. Using PHASE software, four haplotypes were deduced from the two polymorphisms -137G/C (rs187238) and -607C/A (rs1946518), and the haplotype C(-607)G(-137) was significantly associated with LP (P < 0.001). Our data suggest that the identified IL-18 polymorphisms may be associated with the pathogenesis of LP in the present study.
 
Article
Echinoderms are exclusively marine animals. Starfish extracts have drawn attention, because of their wide spectrum of biological effects associated with antifungal, cytotoxic, hemolytic and immunomodulatory activities. The study was carried out to investigate the hemolytic and antinociceptive effect of the methanolic extract of Protoreaster linckii (MEPL) using male albino mice models of chemicals and thermal antinociception. The extract was injected intraperitoneally at doses of 5, 10, 15 and 20 mg/kg. The hemolytic activity was tested against human, chicken, sheep and goat blood red blood cells (RBCs). The percentage of protein was estimated in the crude extract as 4.14%. Among the ten human pathogens tested, Proteus mirabilis showed the most sensitive activity against 0.75 g/ml (9 mm) of sample compared with positive control (15 mm) and Streptococcus pyogenes showed activity at 0.75 g/ml concentration and no activities was noticed at 0.25 and 0.50 g/ml concentration. The hemolytic activity was high in human blood (128 HU). The crude extract shows dose dependent analgesic effect in male albino mice. The maximum mortality was noticed at 100% concentration, that is, 93.6±1.2 and minimum amount of mortality was noticed at 20% concentration, that is, 22.0±2.1 in brine shrimp cytotoxicity assay. The results from the present study appear to support the steroids belief in the medicinal properties of P. linckii against pain in which the central antinociception activity was found and it has also showed good cytolytic properties against blood RBCs.
 
Article
19F NMR provided a highly specific tool for identification of efavirenz in human serum and pharmaceutical preparations as well as a suitable analytical technique for their absolute quantification. The method is based on the integration of appropriate signals of efavirenz and potassium fluoride, as an internal standard. The proposed method is simple and reliable, but when it is used without any sample pretreatment, there is a manipulation of large sample volumes and lengthy analysis time. The calibration curve for efavirenz in human serum was linear over the range of 0.8 to 1000 mg L-1, with detection limit of 0.3 mg L-1. The mean error on human serum samples ranged from about -4 to -6%, with relative standard deviations of <8%. The method was also applied successfully for the determination of efavirenz in real pharmaceutical samples, and compared with the results obtained by a reference high-performance liquid chromatography-ultraviolet (HPLC-UV) method.
 
Article
Excoecaria grahamii, African shrub, is used in many West African countries traditional medicine against different diseases, as powerful purgative and biopesticide. There is little works about pharmacological effects of this plant because of its high toxicity. The effects of the aqueous extract of the plant was investigated on rabbit blood pressure and toad isolated and perfused heart activity. Excoecaria grahamii extracts (EGE) injection exhibited a dose dependent blood pressure decrease like acetylcholine effect. This activity was inhibited by atropine, suggesting muscarinic effect. Same results (inhibition effects) were found on both electrical and mechanical actions of toad isolated and perfused heart. Previous results obtained with aqueous extracts on smooth intestine muscle exhibit a muscarinic effect (hypotensive principle) then alcoholic extracts showed hypertensive and cardiotonic effects on rabbit. Our results confirm existence of muscarinic activity on rabbit blood pressure and toad heart activity
 
Article
The aim of this study was to investigate the effect of 2,2,2-trichloroethanol on peptidoglycan-induced murine macrophages inflammation. The effect of 2,2,2-trichloroethanol on the production of TNF-α and IL-6 by murine peritoneal macrophages with peptidoglycan-stimulation were investigated. Also, RAW264.7 macrophages transfected with a NF-κB luciferase reporter plasmid with the stimulation of peptidoglycan were used to test the effect of 2,2,2-trichloroethanol on NF-κB activity. Flow cytometry and Western blotting were used to check the expression levels of toll-like receptor 2 on treated RAW264.7 macrophages. 2,2,2-Trichloroethanol decreased the unregulated levels of IL-6 and TNF-α produced by the peritoneal macrophages stimulation with peptidoglycan. The NF-κB activities of the RAW264.7 macrophages stimulated by peptidoglycan were decreased. 2,2,2-Trichloroethanol decreased the peptidoglycan-induced murine macrophage inflammation response.
 
Article
The aim of this study was to investigate the effect of 2,3,4’,5-tetrahydroxystilbene 2-O-β-D-glucoside (TSG) on vascular endothelial dysfunction in the type 2 diabetes rats, and the possible mechanisms. Sprague-Dawley rats were treated by high-fat diet and intraperitoneal injection of streptozotocin (40 mg/kg) to induce type 2 diabetes. TSG (60 or 120 mg/kg per day) was administered by oral gavage for 6 weeks. The vascular endothelial dysfunction was assessed using isolated aortic ring preparation. Fasting serum insulin (FINS), fasting blood glucose (FBG), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) and free fatty acids (FFA) in serum were measured. The homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. The mRNA and protein expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in the aorta were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western Blot. The results showed that TSG significantly decreased the levels of FBG, HOMA-IR, MDA, TNF-α and FFA and significantly increased the level of SOD. TSG also improved acetylcholine-induced endothelium-dependent relaxation. The expression of eNOS was significantly increased, whereas the expression of ET-1 was significantly decreased in aortas of diabetic rats with TSG treatment. These results demonstrate that TSG prevents vascular endothelial dysfunction in type 2 diabetes rats, and the mechanism may be related to its ability of anti-oxidation, anti-inflammation, improving insulin resistance, up-regulation of eNOS and down-regulation of ET-1.
 
Article
The introduction of the problem-based learning (PBL) may be a very uncomfortable problem for the students originally exposed to the didactic methods of teaching and learning. Our medical and pharmaceutical curriculum is yet to adopt this new method of learning and as such this study looks forward to exposing some aspects of the traditional style as well as introducing to the students the new method using PBL. It is envisaged that in the five-year Pharmacy program, the students would be exposed to and monitored and their academic performance vis-à-vis their professional competencies adjudged using this two styles of teaching anatomy. A total of one hundred and fifty 200 level Pharmacy students were randomly divided into fifteen groups of ten per group during their 2 semester course in Anatomy in the academic year 2007/2008 session. The students were exposed to both the PBL and traditional methods of teaching anatomy alternately. At the end of the period, 150 structured questionnaires wereadministered to the students and analyzed statistically. Results from this preliminary study does show that the PBL method of teaching Anatomy to Pharmacy students has strong positive impact in the general perception and knowledge build of the students in their 200 level studies despite the obvious challenges of the environment.
 
Article
By analyzing outpatient prescribing indicators and prescribing trends, to investigate the effect of academic and administrative intervention. According to World Health Organization (WHO) criteria the retrospective method was used. We sampled from daily prescriptions, computed the daily prescribing indicator and compared the mean of ten days. We sampled 1180 from 36581 prescriptions; percentage of drugs prescribed by generic name (generic name percent) was 69.2%, percentage of prescriptions with an antibiotic prescribed (antibiotic percent) was 39.15%, percentage of prescriptions with an injection prescribed (injection percent) was 22.63%, average number of drug per prescription (drug number) was 2.04, average drug cost per prescription (drug cost) was¥124.30 ($18.24). By comparing the prescribing trends, the drug cost and generic name percent were increasing yearly. Though other indicators had no statistical significance, they had decreasing trend. Academic and administrative interventions have already been made by Chinese medical management; some prescribing indicators are higher than other countries, but the prescribing trends are becoming more and more rational. Key words: Pharmacoepidemiology, hospital pharmacy, prescription, rational use of drugs, antibiotic percent, injection percent.
 
Article
Roselle (Hibiscus sabdariffa Linn) extract has been scientifically proven to possess high antioxidant activity, anti-proliferation and anti-carcinogenic properties. This study was conducted to evaluate the antioxidative capacity of commercialized Roselle juice (RJ) at three storage periods and its anti-proliferative effect on breast (MCF-7 and MDA-MB-231), ovarian (Caov-3) and cervical (HeLa) cancer cell lines. The antioxidant activity of 1 week (WRJ), 1 month (MRJ) and 1 year (YRJ) juice samples each at 0.001 to 10% concentration range were determined through 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay with L-ascorbic acid as positive control. EC 50 values of WRJ, MRJ, and YRJ were found to be 3.733±0.247, 3.717±0.637 and 3.383±0.711%, respectively. These values were compared to 0.217±0.616% for positive control. The difference in antioxidant activity between different storage periods of RJ was not significant (p>0.05) but all samples exhibited increasing activity with increasing concentrations. RJ at the same concentrations were tested using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay on the four cell lines to obtain the percentage viability of the cells. The cells were incubated for 72 h after inoculation with RJ and the control group was without treatment. The IC 50 was found to be highest for Caov-3 cells (2.267±1.193%) whereas MCF-7 cells exhibited the lowest (0.432±0.278%) IC 50 value after treatment with MRJ. All determinations were analyzed using ANOVA through SPSS with p<0.05 considered as significant. Increasing concentrations of sample corresponded to lower percentage viability of cells for all samples, however the interaction within and between cell type and storage period was not significant (p>0.05). The study showed that commercialized Roselle juice has strong antioxidant capacity and anti-proliferative activity on the four cancer cell lines despite different storage periods. However, further study should be conducted to establish its anti-cancer mechanisms.
 
Article
To verify whether leptin attenuated the sensitivity of colon cancer cells to 5-flurouracil (5-FU). HT-29 cells were treated with 5-FU in the absence or presence of various concentrations of leptin. The cytoprotective effect of leptin was detected by MTT and flow cytometer. The expression of caspase-9 was measured by RT-PCR and Western blot analysis. Leptin attenuated the cytotoxic response of HT-29 cells to 5-FU by facilitating cells survival and antagonizing apoptosis. In addition, leptin decreased the expression of caspase-9 in HT-29 cells induced by 5-FU. Leptin treatment reduces the susceptibility of colon cancer cells to 5-FU by promoting cell survival. Attenuation of caspase-9 expression is one of the mechanisms underlying the cytoprotective role of leptin in HT-29 cells.
 
Article
The purpose of this study was to investigate the effect of leptin on the growth of HT-29 colorectal cancer cell line. HT-29 cells were treated with leptin at several concentrations of 0, 5, 50, 100, 200 ng/ml, respectively. Epidermal growth factor (EGF) was taken as the positive control. The effect of leptin on the growth, proliferation and apoptosis of HT-29 colorectal cancer cell line was assayed through drawing growth curve and by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] method and flow cytometry (FCM). According to the growth curve, the cell counts of HT-29 cell line increased in proportion to leptin concentration, varying from 5 to 200 ng/ml at a dose-dependent manner. However, the cell proliferation amounts of 200 ng/ml leptin group were still less than those of the positive control group (EGF). The MTT results were similar to those from cell counting method. Leptin at different concentration levels promoted the growth of HT-29 cell lines in a time- and dosedependent manner, and the proliferation rate varied from 5.1 to 67.9%. FCM analysis showed that leptin can significantly affect cell cycle of HT-29 cells. With increasing concentrations, G0/G1 phase cells decreased gradually, and S and G2/M phase cells rose gradually, but no significant effect of leptin on apoptosis of HT-29 cells was observed. In vitro, leptin could promote growth and proliferation of HT-29 cell line according to the concentration and experimental time, but there was no significant correlation in apoptosis.
 
Article
The present study aims to investigate the change of apoptosis genes expression of HT29 cells induced by Saikosaponin D (SSD), which is the major component of Xiao Chai Hu Tang, the classic Chinese medicine prescriptions. In this study, gene expression profiles of HT29 cells with or without the SSD treatment were obtained by means of using RT ProfilerTMPCR Array Human Apoptosis and quantitative real-time polymerase chain reaction (PCR) and analyzed to detect differential gene expression. According to results of 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, a final concentration of 10 mg /L of SSD for 24 h was used in the SSD group and the growth inhibition rate of HT-29 cells was about 5%. In SSD treated cells, expression levels of 14 kinds of apoptosis genes changed significantly. Compared with the control group, some apoptosis genes such as DIVA, CASP10, and TRAILR were expressed at much higher levels, while some anti-apoptosis gene such as HIAPI, NAIP, BCL2 were also expressed at much higher levels. SSD induces the apoptosis of HT29 through the apoptosis pathway of TRAIL, TRAIL-R and caspase10 and/or caspase8. And these data could provide targets for the treatment of colon cancer.
 
Article
Nasopharyngeal carcinoma (NPC) is an epidemic malignant cancer in Southern China and Southeast Asia. Curcumin, an edible yellow pigment, has been shown to exert an anti-cancer activity in several tumor types. In this study, the effects of curcumin on cell growth and apoptosis were examined in the human NPC cell line CNE-2z, using the 3-(4,5-dimethythiazol-. 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Western blotting and real-time polymerase chain reaction (PCR) were used to quantify pro-and anti-apoptotic gene expression. Curcumin significantly inhibited the growth of CNE-2z cells. Curcumin also induced apoptosis in CNE-2z cells, in a mechanism dependent on activation of Caspase-3, which was associated with Bax up-regulation and Bcl-2 and NF-B down-regulation. Curcumin had no effect on Fas or caspase-8 expression. The results of this study suggest that curcumin induces apoptosis in CNE-2z cells via the intrinsic pathway.
 
Article
To investigate the regulatory role of RhoA/Rho kinase in the effects of fluvastatin (Flu) on the tumor necrosis factor-α (TNF-α) induced expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) which may provide basis for the prevention of arterial thrombosis, HUVECs in logarithmic phase were divided into TNF-α group, Flu group and TNF-α+Flu group. enzyme-linked immunosorbent assay (ELISA), real time polymerase chain reaction (RT-PCR) and western blot assay were employed to detect the content of TF, messenger ribonucleic acid (mRNA) expression of TF and protein expressions of TF and activated RhoA, respectively. Then, Angiotensin II (Ang II) and Y27632 were used to treat these cells which were then divided into control group, TNF-α+Ang II group, AngII group, TNF-α group and TNF-α+Y27632 group. Western blot assay was performed to detect the protein expression of TF. After TNF-α treatment, the content and mRNA and protein expressions of TF were markedly increased when compared with the control group (P<0.05). However, the content and mRNA and protein expressions of TF in Flu group were significantly lower than those in TNF-α group (P<0.05). Our results showed TNF-α could induce TF expression in HUVECs and activate RhoA, which, however, were inhibited by Flu. Ang II treatment could increase the TNF-α induced TF expression in HUVECs which however was inhibited Y27632. Flu could effectively inhibit the TNF-α induced protein and mRNA expressions of TF in HUVECs in which RhoA/Rho signaling pathway may play an important role.
 
Article
This research aimed to analyze the factors of heart cerebrovascular drugs that can lead to adverse reactions (ADRs) and to promote rational clinical drug use. Reports on cases of heart cerebrovascular diseases were collected in our hospital in 2001 to 2010, and medication and the clinical manifestations of the adverse reactions were analyzed. The incidence of adverse reactions was related with age, gender, routes of administration, dosage forms and other factors. The adverse reactions of heart cerebrovascular drugs were mainly related to dosage forms, the injections were especially more likely to cause adverse reactions, and the clinical manifestations were diversified. It was therefore suggested that doctors and patients pay more attention to the adverse drug reactions in the whole medication process.
 
Article
® 375 and 625 significantly increased plasma total cholesterol by 29.4 and 38.1%, HDL- cholesterol by 53 and 83.5%, LDL- cholesterol by 36 and 96% and triglycerides by 18 and 26%, respectively when compared with control. Furthermore, plasma AST and ALT was significantly increased (p<0.05) by 27.7 and 42.6%, and 33 and 44.4%, respectively in the two treated groups when compared with control. Administration of Augmentin ® 375 and 625 also caused significant decrease in hepatic reduced glutathione (GSH) and vitamin C by 35 and 61%, and 38 and 44%, respectively. Similarly, hepatic superoxide dismutase (SOD) and catalase activities decreased significantly by 33 and 56%, and 31 and 48.7%, respectively in the treated group. In addition, Augmentin ® 375 and 625 significantly decreased the hepatic levels of glutathioneS-transferase (GST) by 44.7 and 53.4%, respectively. In conclusion, the result of the present investigation show that two different combinations of amoxicillin/clavulanic acid (Augmentin ® 375and 625) altered enzymatic and non-enzymatic
 
Article
®971P and 974P), and evaluated in terms of drug content, pH, swellability in different media, viscosity, spreadability, skin irritation on rats and time-resolved stability. The in vitro permeation of gentamicin from the hydrogel formulations was carried out in phosphate buffered saline using a modified Franz diffusion apparatus. Results obtained indicate that gentamicin-loaded hydrogels showed good encapsulation, stability, pH-dependent swelling, tolerability on rats, greater percentage drug release than the commercially available gentamicin ointment and pure sample of gentamicin. Overall, Poloxamer 407 hydrogels of gentamicin gave the most desirable properties in terms of drug permeation, spreadability, pH, swellability and viscosity, superior to polyacrylic acids hydrogels of gentamicin. This study has shown that Poloxamer 407 hydrogels of gentamicin could offer a promising approach for topical delivery of gentamicin for the treatment of skin infections caused by gentamicinsusceptible bacteria.
 
Article
The current study aims to explore the possible correlations between detrusor excitability and the expression of C-kit and connexin-43 (Cx43). Fifty-two adult female Sprague Dawley (SD) rats were randomly divided into the normal control (NC), supra-sacral cord injury (SSCI) and sacral cord injury (SCI) groups. Neurogenic bladder models were established. Urodynamic examination, bladder pathological observation and detrusor muscle excitability detection were performed. Meanwhile, the expression of C-kit and Cx43 was detected using immunohistochemistry and Western blot analysis. The detrusor leak point pressure of the SSCI group increased significantly compared to the NC group, whereas that of the SCI group decreased significantly. The spontaneous detrusor muscle contraction frequency of the SSCI group increased significantly compared to the NC group, whereas that of the SCI decreased significantly. The C-kit and Cx43 positive expression in the SSCI was significantly higher than that in the control group, whereas that in the SCI group was significantly lower (P < 0.01) The C-kit and Cx43 protein content in the SSCI group was significantly higher compared to the NC group, whereas that in the SCI group was significantly lower (P < 0.01). Changes in excitability and the expression of C-kit and Cx43 expression contribute to the occurrence of detrusor hyperreflexia and areflexia.
 
Article
This study explores the changes in gene and protein expression of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in aging patients with atrial fibrillation of Xinjiang Uygur and Han nationalities. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the gene and protein expressions of TH and GAP43 in atrial tissues of 54 patients with valvular heart disease. Comparison of the mRNA and the protein expression of GAP43 and TH between the sinus rhythm group and the atrial fibrillation group was statistically significant (P < 0.05); the protein expression of GAP43 and TH in patients of Xinjiang Uygur and Han nationalities in the sinus rhythm group and atrial fibrillation group was statistically significant (P < 0.05); the protein expression of GAP43 and TH in patients of different nationalities in the sinus rhythm group and atrial fibrillation group was not statistically significant (P > 0.05); the protein expression of GAP43 and TH in patients of different nationalities with different ages in the sinus rhythm group and atrial fibrillation group was not statistically significant (P < 0.05); only the protein expression of GAP43 in patients with different ages in the atrial fibrillation group was statistically significant (P < 0.05). The changes in mRNA and protein expression of TH and GAP43 played a vital role in the process of maintaining atrial fibrillation. The increase in the expression of TH and GAP43 may be one of the molecular bases of the left atrial myoelectricity remodeling of aging patients with atrial fibrillation. TH and GAP43 may be the potential therapeutic targets of atrial fibrillation.
 
Article
Previous evidence demonstrated the antitumor ability of quinazolines and its derivatives. In this study, the anticancer activities of N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride against four kinds of cell lines were evaluated by 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The bioassay results indicated that title compound possessed wide spectrum of anticancer activity. Androgen-independent prostate cancer (PC-3) cells were employed and microscopic observation, lactate dehydrogenase (LDH) release assay, and Western blot were performed to study the antitumor mechanism of N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4-amine dihydrochloride against tumor cells. It was found that title compound executed anticancer activity in a dose-dependent manner with 24.46 μM IC50 of 72 h treatment. Microscopic observation and LDH release assay showed that the compound exerted such an effect through antiproliferation pathway rather than cytotoxicity. Furthermore, Western blot analysis revealed that treatment of cells with N-(4-chlorophenyl)-5,6,7trimethoxyquinazolin-4-amine dihydrochloride (at more than 10 μM for 30 min) resulted in an almost complete inhibition of epidermal growth factor (EGF) induced phosphorylation of extracellular signalregulated protein kinase1/2 (ERK1/2) which suggests that its antiproliferation effect is linked to its inhibition of ERK1/2 activation. These data imply that N-(4-chlorophenyl)-5,6,7-trimethoxyquinazolin-4amine dihydrochloride is a potential anticancer agent capable of antiproliferation activity.
 
Article
The aim of this study was to investigate the medication status of 508 patients with type IIdiabetes admitted to Huashan Hospital, and to guide their clinical medication. The data of the 508 patients with type II diabetes who were admitted to Huashan Hospital between July, 2010 and December, 2010 were collected and analyzed. In 508 patients, acarbose was the most frequently prescribed medication (n = 337, 66.34%), the highest frequency of acarbose was 66.34% (n = 337). Metformin which belongs to the biguanide group accounted for 20.28%. Pioglitazone which belongs to thiazolidinedione group had the lowest frequency of use, and was only 1.38% (n = 7), and patients were often treated with combination therapy (n = 194, 38.18 %). A total of 431 patients (85%) had chronic diabetes complications (state which ones: macro or micro vascular complications). Among the diabetic patients, age groups in 40 to 80 had the highest probability of illness and the incidence rate increases with age; therefore, this group should take regular medical examinations to prevent diabetes induced complications. In the choice of medication, prescription drugs like acarbose and other α-glucosidase inhibitors, at the same time, combined medication with pancreatic kinionogenase are preferred. Enteric-coated tablets or other drugs to treat high blood pressure diabetes, heart disease, nervous system damage and other complications are also recommended.
 
Statistical data of calibration curves of carboxylic acid metabolite of clopidogrel in spiked human plasma. 
HPLC chromatogram of carboxylic acid metabolite of clopidogrel and internal standard (IS). Plasma sample spiked with clopidogrel carboxylate metabolite and IS; Peaks: 1, IS; 2, clopidogrel carboxylate acid metabolite. 
Average plasma drug concentration versus time profile determined after oral administration of clopidogrel (dose 600 mg). (A) Plasma concentration profile for total 80 patients; (B) plasma concentration profile for 3 subgroups (upper, lower and trimmed) compared to the 80 patients. Two additional time points were assumed (time to reach C max for both trimmed (1.75 h) and upper 15% (1.35 h). 
Laboratory findings of patients included in the study. 
Pharmacokinetic parameters of clopidogrel carboxylic acid in patients after taking 600 mg clopidogrel. 
Article
Clopidogrel is an oral antiplatelet drug. Loading dose of 600 mg clopidogrel was shown to improve clinical outcome in patients following percutaneous coronary intervention (PCI). Wide inter-individual variation has been detected in clopidogrel response that can be related to variation in Clopidogrel serum concentration. The aim of this study was to assess the pharmacokinetics parameters of 600 mg loading dose clopidogrel among Jordanian patients undergoing PCI. Additionally, the development of a simple and a validated High-performance liquid chromatography (HPLC) method for the quantification of clopidogrel carboxylate was described. 80 patients who received a loading of 600 mg Clopidogrel were included in our study, several blood samples were collected at different time points. Validated reverse phase HPLC method was used to determine Clopidogrel carboxylic acid metabolite. Non-compartmental analysis was used to determine peak plasma concentration (C max), time to peak plasma concentration (T max), elimination half-life (t 1/2e), and area under the curve (AUC). The pharmacokinetic-parameters were characterized by considerable inter-individual differences [C max =24.49±11.64 µg/ml, T max =2.02±1.52 h, AUC 0→∞ = 123.17± 54.6 mg/ml.h, and t1 ⁄ 2e=4.29±2.92 h]. 15% of the patients who had less than one third of the Cmax 8.09±2.34 µg/ml had delayed T max of 4.17±1.76 h, which was not explained by standard in vitro dissolution test. Pharmacokinetic parameters of 600 mg Clopidogrel showed marked inter-individual differences. The low plasma concentrations in some of the patients and the high inter-individual variability may contribute to reported cases of resistance to Clopidogrel therapy. Further studies are needed to explain low C max and delayed T max values in some patients.
 
Article
The current study investigated toltrazuril/polyethyleneglycol 6000 solid dispersions (toltrazuril/PEG6000 SDs) with improved solubility. The SDs were prepared by solvent-melting method with PEG 6000 as carrier. It was validated by differential thermal analysis (DTA) and cumulative dissolution rate. The solubility of toltrazuril, physical mixture and SDs were measured. The ultra violet (UV) spectrophotometer method was developed for the determination of toltrazuril. It was found that the spectra of cumulative dissolution rate, DTA of the SDs were different from the toltrazuril and physical mixture. Solubility of toltrazuril was enhanced for the formation of SDs. The calibration curve was linear with a correlation coefficient r = 0.9998 in range of 4.0~20.0 µg/mL. The method was simple and practical in preparation and determination the toltrazuril SDs.
 
Top-cited authors
Anthony Jide Afolayan
  • Fort Hare University
Etinosa O. Igbinosa
  • University of Benin
Charles Fokunang
  • THE UNIVERSITY OF BAMENDA
N.M. Guedje
  • University of Yaounde I
Jinous Asgarpanah
  • Islamic Azad University Tehran Medical Sciences