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1.  Prevalence, social acceptance, and awareness of waterpipe smoking among dental university students: a cross sectional survey conducted in Jordan 
BMC Research Notes  2014;7(1):832.
Waterpipe tobacco smoking is increasing in popularity especially among young adults. This spread could be related to limited knowledge of the negative health effects of waterpipe smoking. In this study, prevalence, social acceptance, and awareness of waterpipe smoking were examined among dental university students.
This is a cross-sectional survey study, where a self-administered questionnaire was completed by a sample of dental university students in Jordan.
Students (n = 547) reported current tobacco use of 54.3% for males versus 11.1% for females (P <0.005). Among current smokers, 3.5% used only cigarettes (22.0% males, 2.3% females), 12.6% used only waterpipe (36.6% males, 88.6% females), and 6.9% used both (41.5% males, 9.1% females). Approximately, 70% of males and 42.5% of females who used waterpipe reported smoking mostly at a café. Nearly half of the females reported that they smoke at home in the presence of parents. Among participants, 33.3% of males and 62.5% of females reported indifferent parents’ reaction regarding their waterpipe smoking. Approximately one third of students agreed with the statement that waterpipe smoking is less harmful to oral health than cigarette smoking. About 50-70% of students agreed that waterpipe smoking causes halitosis, delays wound healing time, is associated with dental implant failure, and increases the risk of dental decay.
In this sample, waterpipe tobacco smoking was more common than cigarette smoking among dental students, especially females. This could be an implication of social acceptance of waterpipe leading to its predominance, and thus, the gradual replacement of cigarette smoking with waterpipe smoking. Additionally, dental students’ awareness about the harms of waterpipe is not optimal, and steps are needed to ensure providing such knowledge to students.
PMCID: PMC4253988  PMID: 25421621
Tobacco; Oral health; Awareness; Attitude
2.  Primary Headache in Yemen: Prevalence and Common Medications Used 
Background and Objective. Primary headaches is a major medical concern in certain Arabic countries, for example Oman, Jordan, and Qatar. This study was aimed at increasing understanding of the prevalence of headache in Arabic countries and identifying common medications used for treatment because of the lack of research done in this field in Yemen. Methods. This is a cross-sectional observational study conducted by recruiting case-series of adults and elderly who have primary headache within the age group from 18 to 85 years. 12640 subjects received a simple explanation for the aim of the study as ethical issue. The subjects were allowed to complete a self-conducted screening questionnaire. The data were diagnosed according to the International Headache Society's diagnostic criteria (2004). Results. The results showed that 76.5% of the primary headache is prevalent at least once per year, 27.1% of the tension type headache (TTH) was the maximum percentage of type of headache, and 14.48% of the migraine headache (MH) was the minimum percentage. On the other hand, the relationship between the primary headache and age of subjects was statistically significant (P < 0.05), while between primary headache and sex was not (P > 0.05). In addition, 70.15% of the subjects said that headache attacks affected their activity of daily livings (ADL). 62.26% of the subjects used the medications without medical advice regarding their headache. 37.73% of the subjects relied on medical professionals (physicians and pharmacist) regarding analgesics use. The most common agent used among the medications was paracetamol (38.4%). Others included ibuprofen, aspirin, diclofenac sodium, naproxen, mefenamic acid, ergotamine and (11.45%) were unknown agents. Conclusion. We concluded that absence of health attention from the Yemeni Community and education from the health system in the country regarding analgesics use and their potential risk led to abuse of such medications and could be a reason beyond high prevalence of headache in Yemen.
PMCID: PMC4236899  PMID: 25538854
3.  Level and significance of plasma myeloperoxidase and the neutrophil to lymphocyte ratio in patients with coronary artery disease 
Inflammation plays a pivotal role in the etiology of coronary artery disease (CAD). Myeloperoxidase (MPO) is a potent inflammatory factor and a critical modulator of coronary inflammation and oxidative stress. The goal of this study was to determine the impact of the plasma MPO (pMPO) level and neutrophil/lymphocyte ratio on the clinical characteristics and outcomes of patients with CAD. Blood samples were collected from 210 patients with underlying chest pain or recent myocardial infarction (MI) prior to coronary angiography in order to measure pMPO levels. The pMPO levels and neutrophil/lymphocyte ratio were correlated with clinical characteristics and outcomes following catheterization. The pMPO level and neutrophil/lymphocyte ratio were higher in patients with recent MI than in patients with CAD (coronary occlusion ≥50%) or without CAD (coronary occlusion <50%). Patients with ST segment elevated MI (STEMI) had a higher neutrophil/lymphocyte ratio relative to patients with non-STEMI. The pMPO level was identified to correlate with the neutrophil/lymphocyte ratio and the need for coronary artery reperfusion by coronary artery bypass surgery or percutaneous coronary intervention. Patients who were taking aspirin had lower pMPO levels and neutrophil/lymphocyte ratio compared with those who were not taking aspirin. The plasma neutrophil/lymphocyte ratio was negatively associated with the left ventricular ejection fraction at baseline and the 30-day follow-up, whereas pMPO showed no correlation. Multivariate analysis indicated that the pMPO level was positively associated with MI, the neutrophil/lymphocyte ratio and coronary intervention. The preoperative use of aspirin was associated with a lower pMPO level and neutrophil/lymphocyte ratio. In conclusion, pMPO is positively associated with MI, the neutrophil/lymphocyte ratio and coronary intervention. The preoperative use of aspirin is associated with a lower pMPO level and neutrophil/lymphocyte ratio. pMPO may serve as a predictor of coronary intervention and as a potential therapeutic target for the reduction of inflammation in patients with CAD.
PMCID: PMC4218701  PMID: 25371762
myeloperoxidase; neutrophil; myocardial infarction; coronary artery disease
4.  Impact of aldosterone antagonists on the substrate for atrial fibrillation: Aldosterone promotes oxidative stress and atrial structural/electrical remodeling 
International journal of cardiology  2013;168(6):5135-5142.
Atrial fibrillation (AF), the most common cardiac arrhythmia, is an electrocardiographic description of a condition with multiple and complex underlying mechanisms. Oxidative stress is an important driver of structural remodeling that creates a substrate for AF. Oxidant radicals may promote increase of atrial oxidative damage, electrical and structural remodeling, and atrial inflammation. AF and other cardiovascular morbidities activate angiotensin (Ang-II)-dependent and independent cascades. A key component of the renin–angiotensin-aldosterone system (RAAS) is the mineralocorticoid aldosterone. Recent studies provide evidence of myocardial aldosterone synthesis. Aldosterone promotes cardiac oxidative stress, inflammation and structural/electrical remodeling via multiple mechanisms. In HF patients, aldosterone production is enhanced. In patients and in experimental HF and AF models, aldosterone receptor antagonists have favorable influences on cardiac remodeling and oxidative stress. Therapeutic approaches that seek to reduce AF burden by modulating the aldosterone system are likely beneficial but underutilized.
PMCID: PMC4062912  PMID: 23993726
Aldosterone; Aldosterone antagonist; Atrial fibrillation; Oxidative stress
5.  CO Exposure and Puff Topography Are Associated With Lebanese Waterpipe Dependence Scale Score 
Nicotine & Tobacco Research  2013;15(10):1782-1786.
Waterpipe tobacco smoking involves self-administration of the dependence-producing drug nicotine. Few studies have examined if dependence in waterpipe smokers influences toxicant exposure and smoking behavior.
Current waterpipe tobacco smokers were categorized based on Lebanese Waterpipe Dependence Scale-11 (LWDS-11) score (LWDS-11: LOW < 7; N = 59; HIGH > 13; N = 59). Participants abstained from smoking for 12 hr and then completed a single 30-min waterpipe tobacco smoking episode. Expired-air carbon monoxide (CO) was measured before and 5 min after smoking and puff topography was measured during smoking.
Total mean smoking time was 30.9 min (SD = 3.5) and did not differ significantly by LWDS-11 score. CO boost was greater for participants in the HIGH versus LOW groups (62.3 vs. 43.6 ppm, p < .01). Similarly, those in the HIGH versus LOW group took more puffs (198.6 vs. 157.1 puffs, p < .01), longer duration puffs (2.7 vs. 2.3 s, p < .05), puffs with lower flow rate (10.3 vs. 12.6 L/min, p < .01), and less time between puffs (8.0 vs. 12.4 s, p < .001).
The puff topography of waterpipe tobacco smokers can be predicted by LWDS-11 score, with those scoring higher taking longer duration and lower velocity puffs at a higher frequency. These behavioral differences may underlie the 40% greater CO exposure observed for those with higher LWDS-11 scores. To the extent that waterpipe dependence is associated with more smoke inhalation, more dependent smokers will be exposed to greater amounts of toxic smoke constituents.
PMCID: PMC3842104  PMID: 23616231
6.  Metformin Eased Cognitive Impairment Induced by Chronic L-methionine Administration: Potential Role of Oxidative Stress 
Current Neuropharmacology  2014;12(2):186-192.
Chronic administration of L-methionine leads to memory impairment, which is attributed to increase in the level of oxidative stress in the brain. On the other hand, metformin is a commonly used antidiabetic drug with strong antioxidant properties. In the current study, we tested if chronic metformin administration prevents memory impairment induced by administration of L-methionine. In addition, a number of molecules related to the action of metformin on cognitive functions were examined. Both metformin and L-methionine were administered to animals by oral gavage. Testing of spatial learning and memory was carried out using radial arm water maze (RAWM). Additionally, hippocampal levels or activities of catalase, thiobarbituric acid reactive substances (TBARs), glutathione peroxidase (GPx), glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio were determined. Results showed that chronic L-methionine administration resulted in both short- and long- term memory impairment, whereas metformin treatment prevented such effect. Additionally, L-methionine treatment induced significant elevation in GSSG and TBARs, along with reduction in GSH/GSSG ratio and activities of catalase, and GPx. These effects were shown to be restored by metformin treatment. In conclusion, L-methionine induced memory impairment, and treatment with metformin prevented this impairment probably by normalizing oxidative stress in the hippocampus.
PMCID: PMC3964748  PMID: 24669211
Memory; learning; hippocampus; maze; oxidative stress; L-methionine; metformin.
7.  Lack of Association between Polymorphisms of Hepatic Lipase with Lipid Profile in Young Jordanian Adults 
Lipid insights  2014;7:1-5.
The human hepatic lipase (LIPC) gene encodes hepatic lipase, an enzyme involved in lipoprotein metabolism and regulation. Therefore, variants in LIPC gene may influence plasma lipoprotein levels. In this study, the association of LIPC C-514T and G-250A polymorphisms with plasma lipid profiles in 348 young Jordanians was investigated. Genotyping of C-514T and G-250A was performed by polymerase chain reaction and subsequent digestion with DraI and NiaIII restriction enzymes, respectively, while Roche analyzer was used to determine plasma total cholesterol, triglycerides, low-and high-density lipoprotein. The G-250 and C-514 alleles were most abundant in Jordanians with 79 and 80% frequencies, respectively. Additionally, no difference was found in the lipid–lipoprotein profile between the different genotype groups of C-514T or G-250A polymorphisms, even when males and females were examined separately (P > 0.05). In young Jordanian adults, the examined LIPC polymorphisms seem to play a limited role in determining the lipid profile.
PMCID: PMC4167487  PMID: 25278769
Hepatic lipase; lipid profile; Jordan; polymorphism; LIPC
8.  Tempol protects human lymphocytes from genotoxicity induced by cisplatin 
The use of cisplatin in treatments of human malignancies is limited by its side effects that include DNA damage and the subsequent risk of developing secondary cancer. In this study, we examined the possible protective effect of Tempol against DNA damage induced by cisplatin in human lymphocytes using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) assays. Cisplatin induced significant elevation in the frequencies of CAs and SCEs in cultured human lymphocytes (P < 0.01). Treatment of lymphocytes with Tempol significantly lowered CAs and SCEs induced by cisplatin. Tempol alone did not affect spontaneous levels of SCEs and CAs observed in the control group (P > 0.05). In conclusion, Tempol protects human lymphocytes against genotoxicity induced by the anticancer drug cisplatin.
PMCID: PMC4057850  PMID: 24955171
Cisplatin; Tempol; chromosomal aberrations; sister chromatid exchanges; oxidative stress
9.  Synthesis, In Vitro and In Vivo Evaluation of the N-ethoxycarbonylmorpholine Ester of Diclofenac as a Prodrug 
Pharmaceuticals  2014;7(4):453-463.
The N-ethoxycarbonylmorpholine moiety was evaluated as a novel prodrug moiety for carboxylic acid containing drugs represented by diclofenac (1). Compound 2, the N-ethoxycarbonylmorpholine ester of diclofenac was synthesized and evaluated as a potential prodrug. The stability of the synthesized prodrug was evaluated in solutions of pH 1 and 7.4, and in plasma. The ester’s half lives were found to be 8 h, 47 h and 21 min in pH 1, pH 7.4 and plasma, respectively. Equimolar doses of diclofenac sodium and its synthesized prodrug were administered orally to a group of rabbits in a crossover study to evaluate their pharmacokinetic parameters. The prodrug 2 shows a similar rate and extent of absorption as the parent drug (1). The ulcerogenicity of the prepared prodrug was evaluated and compared with the parent drug. The prodrug showed less ulcerogenicity as detected by fewer number and smaller size of ulcers. In conclusion, the newly synthesized N-ethoxycarbonylmorpholine ester of diclofenac prodrug showed appropriate stability properties at different pHs, similar pharmacokinetic profile, and much less ulcerogenecity at the GIT compared to the parent drug diclofenac.
PMCID: PMC4014702  PMID: 24736104
diclofenac; prodrug; ethoxycarbonylmorpholine; pharmacokinetics; ulcerogenicity; prodrug hydrolysis
10.  Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme 
The dipeptidyl peptidase-IV (DPP-IV) enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels.
In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point.
Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 μM concentration.
The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.
PMCID: PMC3896277  PMID: 24470754
diabetes mellitus; dipeptidyl peptidase-IV; aminobenzamide derivatives; hypoglycemic activity; CDOCKER software
11.  Exposure of Pregnant Women to Waterpipe and Cigarette Smoke 
Nicotine & Tobacco Research  2012;15(1):231-237.
Throughout the Eastern Mediterranean region, tobacco is used primarily in 2 forms: cigarette smoking and waterpipe smoking. Despite the fact that tobacco use is considered as a global public health threat, waterpipe smoking is reported to be growing in popularity, particularly among women. The objectives of this study are to determine the prevalence and patterns of cigarette, waterpipe, and passive smoking among pregnant women in Jordan, and to assess their perception of harmful effects of cigarette and waterpipe smoking.
A total of 500 pregnant women were randomly recruited from maternity clinics in North and Middle of Jordan and surveyed regarding exposure to waterpipe tobacco and cigarette smoking.
The results showed that 7.9% of women were current cigarette smokers and 8.7% were current waterpipe smokers. About 82.4% of all women reported that they are exposed to cigarette smoke and 32.8% reported that they are exposed to waterpipe smoke. The most common place where women are exposed to cigarette and waterpipe smoke was their house (50.4% and 48.7%, respectively) followed by public places (31.4% and 21.4%, respectively). In addition, the husband was the main source for exposure to cigarette and waterpipe smoke (48.5% and 42.7%, respectively). Approximately, 74% of women believed that cigarette smoking is addictive, whereas only 55.1% reported that waterpipe smoking leads to addiction.
Exposure of pregnant women to tobacco smoke is a public health problem in Jordan that requires immediate action.
PMCID: PMC3524068  PMID: 22573726
12.  Distribution Of CCR-5Δ32, CCR2-64I, and SDF-1-3′A Alleles Among Jordanians 
Entry of HIV virus into cells is mediated by chemokine receptors. Genetic variations in chemokine receptors have been shown to modulate susceptibility to HIV infection and disease course. In this study, the frequencies of CCR5 (CCR5-Δ32), CCR2 (CCR2-64I), and SDF-1 (SDF-1-3′) gene polymorphisms were determined in a Jordanian population. A total of 540 subjects were randomly selected from different regions of Jordan (South, Middle, and North). Six individuals were found to carry the CCR5-Δ32 allele (0.6%) and only in the heterozygous genotype. The frequencies of CCR2-64I and SDF1-3′A were 17.5% and 34.2%, respectively. In addition, no significant difference in the distribution of the examined polymorphisms among different regions of Jordan was detected. In conclusion, the CCR5-Δ32 allele is rare, whereas the CCR2-64I and SDF1-3′A alleles are common among Jordanians.
PMCID: PMC3537295  PMID: 22770415
13.  Exploring behavioral and molecular mechanisms of nicotine reward in adolescent mice☆ 
Biochemical pharmacology  2011;82(8):10.1016/j.bcp.2011.06.019.
Tobacco smoking during adolescence has become a prominent preventable health problem faced in the United States. Addictive properties of smoking are thought to have a pronounced effect at a young age, thereby increasing vulnerability to a life-long addiction and decreasing the likelihood of smoking cessation during adulthood. Learning and memory involvement in nicotine reward was assessed in early adolescent (PND 28–34) and adult (PND 70+) male ICR mice by conducting conditioning sessions of nicotine (0.5 mg/kg) acquisition at varying time-spans, and evaluating extinction and reinstatement of nicotine preference using Conditioned Place Preference. Acquisition studies resulted in a significant preference for nicotine after 3 days of conditioning for both age groups, but not after only 1 or 2 conditioning days. In the extinction study, adolescent mice exhibited preference for nicotine 72 h after the last conditioning session, whereas preference for nicotine was extinct in adult mice by 72 h. Reinstatement studies showed adolescent mice, but not adult mice, recovering nicotine preference after a priming injection of 0.1 mg/kg nicotine on day 9 after the mice underwent extinction. No significant differences were found when nAChRs were quantified in both early adolescent and adult mice using binding techniques including cytisine sensitive, α-conotoxin-MII sensitive, and α-bungarotoxin sensitive nAChRs. Levels of striatal dopamine release were measured in both age groups using a dopamine release assay over a range of nicotine doses, which also resulted in no significant differences. More sensitive assays may facilitate in understanding the mechanisms of nicotine reward in adolescent mice.
PMCID: PMC3821840  PMID: 21708139
Nicotine; Adolescence; Reward; Conditioned place preference; Mice
14.  Atorvastatin treatment modulates the interaction between leptin and adiponectin, and the clinical parameters in patients with type II diabetes 
The aim of this study was to examine the effect of atorvastatin treatment on levels of leptin, adiponectin and insulin resistance, and their correlation with clinical parameters, in patients with type II diabetes. Patients with diabetes (n=394) were divided into two groups, comprising 161 patients who received 20 mg/day atorvastatin (statin group), and 233 patients who did not receive statins (statin-free group). The results showed that atorvastatin treatment of patients with diabetes was not associated with changes in leptin, adiponectin, the leptin/adiponectin (L/A) ratio or homeostasis model assessment-insulin resistance (HOMA-IR). However, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol (Tchol) were positively correlated with leptin and L/A ratio in the statin group only (P<0.05). By contrast, high-density lipoprotein cholesterol (HDL-C) showed a significant positive correlation with adiponectin in the statin and statin-free groups (P<0.05). Additionally, a positive correlation was found between HOMA-IR and glycated hemoglobin (HbA1c), and TG, in both groups, whereas Tchol was positively correlated with HOMA-IR in the statin group only (P<0.05). When multivariate analysis was performed with HOMA-IR as the dependent variable, and with adjustment for age, body mass index (BMI) and waist circumference, HbA1c was found to be a significant predictor of HOMA-IR or insulin resistance. In conclusion, atorvastatin treatment may have several effects on the interaction between leptin and adiponectin, and on clinical parameters in patients with type II diabetes.
PMCID: PMC3829757  PMID: 24255692
adiponectin; leptin; statins; insulin resistance; lipid panel
15.  Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung 
Inhalation toxicology  2012;24(10):667-675.
Tobacco smoking represents a global public health threat, claiming approximately 5 million lives a year. Waterpipe tobacco use has become popular particularly among youth in the past decade, buttressed by the perception that the waterpipe “filters” the smoke, rendering it less harmful than cigarette smoke.
In this study, we examined the acute exposure of waterpipe smoking on lung inflammation and oxidative stress in mice, and compared that to cigarette smoking.
Materials and methods
Mice were divided into three groups; fresh air control, cigarette and waterpipe. Animals were exposed to fresh air, cigarette, or waterpipe smoke using whole body exposure system one hour daily for 7 days.
Both cigarette and waterpipe smoke exposure resulted in elevation of total white blood cell count, as well as absolute count of neutrophils, macrophages, and lymphocytes (P < 0.01). Both exposures also elevated proinflammatory markers such as TNF-α and IL-6 in BALF (P < 0.05), and oxidative stress markers including GPx activity in lungs (P < 0.05). Moreover, waterpipe smoke increased catalase activity in the lung (P < 0.05). However, none of the treatments altered IL-10 levels.
Discussion and conclusion
Results of cigarette smoking confirmed previous finding. Waterpipe results indicate that, similar to cigarettes, exposure to waterpipe tobacco smoke is harmful to the lungs.
PMCID: PMC3752682  PMID: 22906173
Acute waterpipe smoke exposure; cigarette smoking; inflammation; lungs; oxidative stress
16.  Antimicrobial Activity of Common Mouthwash Solutions on Multidrug-Resistance Bacterial Biofilms 
Periodontal bacteria occur in both planktonic and biofilm forms. While poor oral hygiene leads to accumulation of bacteria, reducing these microbes is the first step toward good oral hygiene. This is usually achieved through the use of mouthwash solutions. However, the exact antibacterial activity of mouthwash solution, especially when bacteria form biofilms, is yet to be determined. In this study, we evaluated the antibacterial activity of common mouthwash solutions against standard bacteria in their planktonic and biofilm states.
Standard bacterial strains were cultured, and biofilm were formrd. Thereafter, using standard method for determination of minimum inhibitory concentrations (MIC) values of various mouthwash solutions were determined.
Results show that common mouthwash solutions have variable antibacterial activity depending on their major active components. Only mouthwash solutions containing chlorohexidine gluconate or cetylpyridinum chloride exhibited activity against majority, but not all tested bacterial strains in their biofilm state. Additionally, bacteria are generally less susceptible to all mouthwash solutions in their biofilm as compared to planktonic state.
While mouthwash solutions have variable antibacterial activity, bacteria in their biofilm state pose a challenge to dental hygiene/care where bacteria become not susceptible to majority of available mouthwash solutions.
PMCID: PMC3748664  PMID: 23976912
Mouthwash; Antimicrobial; Biofilm; Planktonic
17.  Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis 
In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID]) and 5-[4-(benzoxazol-2-yl-5-acetic acid)phenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA]) are reported. The structures of the synthesized compounds were confirmed using infrared (IR), hydrogen-1 nuclear magnetic resonance (1H NMR), and mass spectrometry (MS) spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB)-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis.
PMCID: PMC3749060  PMID: 23983456
benzoxazole acetic acid; azo prodrug; colon drug delivery
The aim of this study was to investigate the genotoxicity of waterpipe smoking in the lymphocytes of waterpipe smokers using chromosomal aberrations (CAs) assay.
Materials and Methods
Fifty waterpipe smokers and 18 healthy non-smokers volunteered to participate in the study. Additionally, 18 heavy cigarette smokers were recruited for comparison. Chromosomal aberrations (CAs) assay was used to evaluate DNA damage in the lymphocytes.
The results showed that similarly to cigarette smoking, waterpipe smoking significantly increased the frequencies of CAs (p < 0.01). In addition, the frequencies of CAs increased with more waterpipe use.
Waterpipe smoking causes DNA damage to lymphocytes and the damage increases with more waterpipe use.
PMCID: PMC3724222  PMID: 22729491
Waterpipe; Smoking; Cigarette; Chromosomal aberrations
19.  In vitro determination of the antibiotic susceptibility of biofilm-forming Pseudomonas aeruginosa and Staphylococcus aureus: possible role of proteolytic activity and membrane lipopolysaccharide 
We carried out a comprehensive overview of inhibitory effects of selected antibiotics on planktonic and biofilm cells of Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (ATCC 27853) strains. The possible involvement of protease activity and the lipopolysaccharide (LPS) profile of P. aeruginosa were also analyzed. Biofilm cells of both strains were more resistant to antibiotics than their planktonic counterparts. Protease activity was increased in both strains in the biofilm forms. Challenge with sublethal doses of antibiotics also increased proteolytic activity of biofilm cells. Additionally, the LPS profile of P. aeruginosa showed pattern alterations of the biofilm that can contribute to biofilm resistance and survival. These observations provide evidence for the involvement of bacterial proteolytic activity and LPS profile in the resistance of biofilm bacteria to antibiotics compared to their planktonic counterparts.
PMCID: PMC3593709  PMID: 23493936
biofilm; Pseudomonas aeruginosa; Staphylococcus aureus; proteolytic activity; lipopolysaccharide
20.  Effect of statin therapy on vaspin levels in type 2 diabetic patients 
Statins are commonly used antihyperlipidemic agents, with anti-inflammatory and immunomodulatory properties that are thought to account for a significant portion of their ability to protect against atherosclerosis and cardiovascular disease. Vaspin, a visceral adipose tissue-derived serine protease inhibitor, is an emerging adipokine with important insulin-sensitizing, cardioprotective, and antiatherosclerotic properties in patients with diabetes. In this randomized controlled clinical trial, we evaluated the effect of statin therapy on vaspin levels in patients with type 2 diabetes mellitus.
Patients were divided into two groups, ie, those receiving simvastatin (study group, n = 33), and those who did not (control group, n = 29). Patient data, blood biochemistry, and vaspin levels were recorded at the beginning of the study (baseline) and after 8 weeks (end of the study).
After 8 weeks of treatment, vaspin levels were increased in patients treated with simvastatin (504.58 ± 203.07 pg/mL at baseline versus 629.15 ± 68.39 pg/mL after 8 weeks, P < 0.01), but not in patients who were not treated with simvastatin (613.33 ± 357.53 pg/mL at baseline versus 582.37 ± 84.63 pg/mL after 8 weeks, P > 0.05). In addition, the lipid-lowering effect of simvastatin was reflected in a statistically significant reduction in total cholesterol in the study group (220.75 ± 55.66 mg/dL at baseline versus 201.90 ± 53.65 mg/dL after 8 weeks P < 0.01) but not in the control group (214.24 ± 47.2 mg/dL at baseline versus 215.72 ± 43.65 mg/dL after 8 weeks, P > 0.05) and in a statistically significant reduction in triglyceride levels in the study group (265.8 ± 210.41 mg/dL at baseline versus 223.03 ± 178.67 mg/dL after 8 weeks, P < 0.05) but not in the control group (225.44 ± 115.13 mg/dL at baseline versus 215.58 ± 110.2 mg/dL after 8 weeks, P > 0.05). Mean vaspin levels were significantly higher in the study group than in the control group.
These results indicate that statin therapy increases plasma vaspin levels in addition to having a lipid-lowering effect. This could be a mechanism underlying the pleiotropic effects seen with statins, including their cardioprotective and antiatherosclerotic effects.
PMCID: PMC3581289  PMID: 23449848
vaspin; statins; diabetes; adipokines
21.  Waterpipe Tobacco and Cigarette Smoking Among University Students in Jordan 
While waterpipe and cigarette smoking are well studied in Syria and Lebanon, data from Jordan are sparse.
To characterize the relative prevalence of waterpipe tobacco and cigarette smoking among university students in Jordan, and to compare the demographic and environmental factors associated with each form of tobacco use.
We surveyed 1845 students randomly recruited from four universities in Jordan. We used multivariable logistic regression controlling for clustering of individuals within universities to determine associations between demographic and environmental covariates and waterpipe tobacco and cigarette use.
Waterpipe tobacco smoking rates were 30% in the past 30 days and 56% ever, and cigarette smoking rates were 29% in the past 30 days and 57% ever. Past 30-day waterpipe tobacco smoking rates were 59% for males and 13% for females. Compared with males, females had substantially lower odds of being current waterpipe (OR=0.12, 95% CI=0.10–0.15) or cigarette (OR=0.08, 95% CI=0.05–0.14) smokers. Compared with waterpipe tobacco smoking, current cigarette smoking was more significantly associated with markers of high socioeconomic status.
Waterpipe tobacco smoking is as common as cigarette smoking among Jordanian university students. While cigarette smoking is consistently associated with high socioeconomic status, waterpipe tobacco smoking is more evenly distributed across various populations.
PMCID: PMC3570564  PMID: 22525279
hookah; narghile; college; Middle East
22.  Antibacterial activity of statins: a comparative study of Atorvastatin, Simvastatin, and Rosuvastatin 
Statins have several effects beyond their well-known antihyperlipidemic activity, which include immunomodulatory, antioxidative and anticoagulant effects. In this study, we have tested the possible antimicrobial activity of statins against a range of standard bacterial strains and bacterial clinical isolates.
Minimum inhibitory concentrations (MIC) values were evaluated and compared among three members of the statins drug (atorvastatin, simvastatin, and rosuvastatin).
It was revealed that statins are able to induce variable degrees of antibacterial activity with atorvastatin, and simvastatin being the more potent than rosuvastatin. Methicillin-sensitive staphylococcus aureus (MSSA), methicillin-resistant staphylococcus aureus (MRSA), vancomycin-susceptible enterococci (VSE), vancomycin-resistant enterococcus (VRE), acinetobacter baumannii, staphylococcus epidermidis, and enterobacter aerogenes, were more sensitive to both atorvastatin, and simvastatin compared to rosuvastatin. On the other hand, escherichia coli, proteus mirabilis, and enterobacter cloacae were more sensitive to atorvastatin compared to both simvastatin and rosuvastatin. Furthermore, most clinical isolates were less sensitive to statins compared to their corresponding standard strains.
Our findings might raise the possibility of a potentially important antibacterial class effect for statins especially, atorvastatin and simvastatin.
PMCID: PMC3408379  PMID: 22564676
Antimicrobial activity; Statins; Atorvastatin; Simvastatin; Rosuvastatin
23.  Investigation of the antibacterial activity of pioglitazone 
To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria.
Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC) of pioglitazone was measured according to the broth micro incubation standard method.
Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 μM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 ± 3.87 mg/L) to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 ± 3.77 mg/L and MIC = 62.5 ± 4.14 mg/L, respectively). Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 μM) before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae.
These results indicate the possibility of a new and potentially important pioglitazone effect and the authors’ ongoing studies aim to illustrate the mechanism(s) by which this antibacterial effect is induced.
PMCID: PMC3210070  PMID: 22087061
pioglitazone; susceptibility testing; antibiotics; diabetes
24.  Multi-drug resistance 1 genetic polymorphism and prediction of chemotherapy response in Hodgkin's Lymphoma 
The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen.
a total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism.
these studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05).
these results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.
PMCID: PMC3154152  PMID: 21762523
Lymphoma; C3435T SNP; MDR-1
25.  Water pipe tobacco smoking among university students in Jordan 
Nicotine & Tobacco Research  2010;12(6):606-612.
Although water pipe tobacco smoking is common in Lebanon and Syria, prevalence in neighboring Jordan is uncertain. The purposes of this study were (a) to assess the prevalence of water pipe tobacco smoking among university students in Jordan and (b) to determine associations between sociodemographic variables and water pipe tobacco smoking in this population.
A trained interviewer administered a questionnaire among randomly selected students at four prominent universities in Jordan. The questionnaire assessed sociodemographic data, personal history of water pipe tobacco use, and attitudes regarding water pipe tobacco smoking. We used logistic regression to determine independent associations between sociodemographic and attitudinal factors and each of two dependent variables: ever use of water pipe and use at least monthly.
Of the 548 participants, 51.8% were male and mean age was 21.7 years. More than half (61.1%) had ever smoked tobacco from a water pipe, and use at least monthly was reported by 42.7%. Multivariable analyses controlling for all relevant factors demonstrated significant associations between ever use and only two sociodemographic factors: (a) gender (for women compared with men, odds ratio [OR] = 0.11, 95% CI = 0.07–0.17) and (b) income (for those earning 500–999 Jordanian dinar (JD) monthly vs. <250 JD monthly, OR = 2.37, 95% CI = 1.31–4.31). There were also significant associations between perception of harm and addictiveness and each outcome.
Water pipe tobacco smoking is highly prevalent in Jordan. Although use is associated with male gender and upper middle income levels, use is widespread across other sociodemographic variables. Continued surveillance and educational interventions emphasizing the harm and addictiveness of water pipe tobacco smoking may be valuable in Jordan.
PMCID: PMC2878728  PMID: 20418383

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