Imre Annamária, Kolcsár Melinda, Groşan Alexandra, M Imre and Dogaru Maria Titica
Objectives: Venlafaxine is an antidepressant, categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI) with suspected metabolic side effects. The aim of our study was to assess these metabolic effects in rats, using two different doses of venlafaxine.
Materials: Three groups of Wistar rats have been treated with venlafaxine during seven weeks. The rats have received a daily dose of 10mg/kg (D1) and 40 mg/kg (D2) while the control group (Dc) has received no treatment. Rats were given “ad libitum” access to food and water. The rats were weighted at treatment day 0, 7, 14, 21, 28, 35, 42 and 49. After completion of venlafaxine treatment, the rats were sacrificed, blood was harvested and the following biochemical parameters have been determined from the centrifuged plasma: triglycerides, glucose and total cholesterol levels.
Results: Both the 10 mg/kg and the 40 mg/kg dose venlafaxine therapy resulted in a highly significant increase of rat’s weight. Compared with the control group the mean weight of D1 group has increased with 130.5 ±21.79 g (<0.01) while the mean weight of the second group increased with 94±24.16 g (p<0.01). In addition weight gain of D1 group was significantly higher than that of D2 group (p<0.01). Venlafaxine therapy induced significant increase in serum triglyceride levels (140.04±55.46 mg/dL p<0.01, 83.59±52.85 mg/dL p=0.05). This metabolic effect has been shown to be more evident in case of 10mg/kg dose therapy (p=0.03). Simultaneously, serum cholesterol levels have been reduced, however this decrease proved to be significant only in case of group D2 (p=0.03). Despite of increased triglyceride values, glucose levels were significantly decreased in both treated groups (133.33±36.18mg/dL p=0.05, 118.10±51.98 mg/dL p=0.02).
Conclusions: Our results suggest that venlafaxine administrated to rats has unwished dose related metabolic effects such as significant increase in weight and hypertriglyceridemia, however serum cholesterol and plasma glucose levels appears to be decreased by this medication.
Dan Andonie, Zsolt Gáll, Paul Bosa, Maria Titica Dogaru and Szende Vancea
An uncomplicated, sensitive liquid chromatography linked to mass spectrometry (LC/MS) for evaluation of carbamazepine and carbamazepine-10,11-epoxide (its metabolite) in human plasma, human saliva, rat plasma, and rabbit plasma was developed. Analyses were conducted on a Zorbax SB-C18, 100 mm × 3 mm ID, 3.5 μm column, at a column temperature of 40 ºC. The mobile phase was comprised of 0.1% formic acid in water and methanol in a 35 : 65 (v/v) ratio, with a flow rate of 0.4 mL/min. Lacosamide was utilized as internal standard. Under these chromatographic conditions, the retention times of lacosamide, carbamazepine-10,11-epoxide, and carbamazepine were 1.4 min, 1.6 min, and 2.2 min, respectively. The quantification of the analytes was performed using multiple reaction monitoring, with the use of a triple quadrupole mass spectrometer with electrospray positive ionization. The monitored ions were m/z 194 derived from m/z 237 for carbamazepine, m/z 180 derived from m/z 253 for carbamazepine-10,11-epoxide, and m/z 108 derived from m/z 251 for lacosamide. The samples were prepared by protein precipitation from 0.2 mL of plasma/saliva using 0.6 mL of internal standard solution in methanol. Calibration curves were constructed over the ranges 1.1–17.6 µg/mL and 0.23–5.47 µg/mL for carbamazepine and carbamazepine-epoxide, respectively. The coefficients of determination obtained by using a weighted (1/x) linear regression were greater than 0.994. The reported LC-MS/MS method was applied to preclinical pharmacokinetic studies and therapeutic drug monitoring.
Amelia Tero-Vescan, Camil-Eugen Vari, Daniela-Lucia Muntean, Maria-Titica Dogaru, Cristina Filip and Silvia Imre
A simple and selective method for genistein (GNST) determination in rat liver and kidney was validated in order to study the phytoestrogenic effect of GNST in ovariectomised female Wistar rats. GNST was separated on a Kromasil 100-RP8 column, 150 mm x 4.6 mm, 5 mm equipped with a Kromasil RP 8 precolumn. The mobile phase was 55:45 (v / v) phosphoric acid, 15 mmol in water: methanol at a flow rate of 1.3 ml / min. Luteolin 20 μg / ml in methanol was used as internal standard (IS). The retention time of GNST was tR = 13.22 min and tR =11.60 min for the IS. Calibration curves in the range 40-400 μg GNST/100g liver and 20-200 μg GNST/100g kidney presented a coefficient of determination higher than 0.99. The method developed presented a good precision and accuracy at the lower limit of quantification LLOQ. 10 white Wistar female rats, 8 weeks of age were treated s.c. with 10 mg GNST/kg bw/day for 8 weeks, while a group of 10 animals were used as controls. The values obtained for GNST in the liver were 192.12 ± 53.46 μg/100g and 74.51 ± 12.77 μg/100g in kidney samples.
Ruxandra Emilia Ştefănescu, Sigrid Eșianu, Eszter Laczkó-Zöld, Anca Mare, Bianca Tudor and Maria Titica Dogaru
Objectives: The aim of this study was to assess storage effects on anthocyanin and total polyphenol content in different bilberry and blueberry extracts and to evaluate the antioxidant and antibacterial activity of these extracts. Materials and methods: Total phenolic content, total monomeric anthocyanin content and antioxidant activity were determined in the first month and after three months storage of berries at either -20 °C or -50 °C. Two different solvents were used (methanol and 50% ethanol). Antibacterial activity was determined for the 3 months stored fruits using a microdilution method and was expressed as the minimum inhibitory concentration. Results: There were significant differences between the concentration in the first month and after three months storage in both types of fruit extracts. Regarding the extracting solvent, we noticed that total phenols were better extracted with 50% ethanol, while the total monomeric anthocyanin content was higher in the methanolic extracts. No significant or slightly significant differences were observed between the fruits stored at -20 °C or -50 °C. Ethanolic extracts showed the highest scavenging activity. Good antibacterial activity was observed on gram-positive bacteria. Conclusions: Storage conditions are an important factor that can influence chemical composition of fruits. Although freezing is a good option for preservation, our study showed a high decrease in the concentration of total phenols and anthocyanins after only three months. The fruits have shown a high antioxidant activity and a good antibacterial effect. Further studies are needed for better understanding the changes that can appear during the storage.
Stoica Ciprian Mihai, Căldăraru Carmen Denise, Vari Camil Eugen, Tarţa Dorin Ionuţ, Dogaru Maria Titica, Caraşca Emilian and Dogaru Grigore Aloiziu
Background: Therapeutic drug monitoring (TDM) in patients with Chronic Kidney Disease (CKD) with kidney transplant, represents a major post transplant concern due to the characteristics of this special category of patients, particularities which can generate changes of the pharmacokinetic profile of the administered medication.
Material and methods: The current study is a retrospective pharmacokinetic study, over a period of 50 months, including a group of 36 kidney transplanted patients with CKD. Tacrolimus blood concentration was determined by a validated high-performance liquid chromatography method (HPLC), at a 12 hour time interval from the last administration of the immunosuppressive medication and before the following dose (Residual concentration, Cmin(trough)).
Results: During the monitoring of therapy, based on the pharmacokinetic criteria, 252 measurements of blood concentration were determined, 58 of these being outside the therapeutic window.
Conclusions: The results obtained show that it is mandatory to continue to monitor closely medical therapy based on the pharmacokinetic criteria in view of improving drug administration. The other ways of monitoring therapy: the clinical and biochemical criteria should not be overlooked. In addition, the interindividual variability of patients should be considered, as well as drug interaction which can alter the pharmacokinetics of tacrolimus.
Mircea Dumitru Croitoru, Hermina Iulia Petkes, Ibolya Fülöp, Remus Cotârlan, Oana Elena Şerban, Titica Maria Dogaru, Şerban Andrei Gâz Florea, Béla Tőkés and Cornelia Majdik
Free radicals are involved in the development of reperfusion injuries. Using a spin trap, the intensity of such lesions can be reduced. Nitrones (effective in vivo spin traps) were tried in this work as in vivo nitric oxide donors. Nitrite and nitrate concentration values (rabbit blood) were used as biomarkers of nitric oxide production. Most nitrones did not increase plasma concentrations of nitrite and nitrate; on the contrary, reduced plasma concentrations of these indicators were noted. However, glyoxal isopropyldinitrone, in a dose of 50 mg kg-1, was highly effective in increasing nitric oxide production. At the same time, nitrones do not react with hepatic homogenates, proving that the release of nitric oxide takes place in the tissues and is not related to hepatic metabolism. Before using nitrones in vivo, they were tested in vitro for the ability to release nitric oxide following a reaction with the hydroxyl radical.
Stela Mariana Al Hussein, Hussam Al Hussein, Camil Eugen Vari, Nicoleta Todoran, Hamida Al Hussein, Adriana Ciurba and Maria Titica Dogaru
Objective. This study aimed to evaluate the effects of practices and attitudes towards lifestyle in adolescence as risk or protective factors, for both the acne occurrence and lesions’ severity.
Methods. A cross-sectional study based on a self-reported questionnaire was conducted during 4 months on 148 high school students, aged 16-20 years, in a high school community of Tîrgu Mureș. Acne prevalence and severity, demographic and anthropometric characteristics, the family history of acne vulgaris, smoking behavior and the weekly intake of certain food categories supposed to increase the risk of acne vulgaris were evaluated. Statistical analysis was performed in terms of Odds ratio, Confidence Interval and Chi-square (p<0.05) methods.
Results. In the investigated community, acne prevalence was found of 47.30%, while 78 subjects (control group) had no facial acne lesions. In acne group: 57.1% had family history of acne, 62.9% were smokers, 22.9% were overweight or obese and 84.3% did not receive any dietary information from specialists. 41.4% were not fish consumers, while 74.3% rarely or never were eating fruits and vegetables. Statistically significant differences between the two analyzed groups were found in terms of sweets, carbonated drinks, dietary fat, white bread, fish, fruits and vegetables weekly intake.
Conclusions. Family history, smoking behavior, excessive dietary fat, sweets, carbonated drinks and white bread could be considered as risk factors in acne vulgaris. An increased weekly intake of fish, vegetables and fruits, may have a protective effect in acne development or severity.
Stela Mariana Al Hussein, F. Buicu, Dalila Maier, H. Al Hussein, Adriana Ciurba, Hamida Al Hussein and Maria Titica Dogaru
Objectives: The aim of this study was to compare the efficacy and tolerability of 20% trichloroacetic acid (TCA) peel with 15% azelaic acid gel, a standard antiacne topical treatment.
Materials and methods: 51 patients aged between 16-40 years, with mild and moderate acne, were randomized into two groups. Before the treatment were investigated the patients clinical features and hygienic habits, the previous antiacne treatments and feed-back to them. No cases under treatment with contraceptive pills or antiacne medication that could interfere with the results, were included. For a period of eight weeks, 27 patients (group A) were treated with 15% azelaic acid gel, twice daily, and 24 patients (group B) underwent four sessions of 20% TCA peels, at 14 days interval. The efficacy was evaluated by acne lesions counting, at baseline and at 8 weeks. Adverse effects incidence (erythema, local skin irritation), as well as the satisfaction degree of patients, were investigated.
Results: Was observed a mean reduction in the number of acne lesions of 32,36% for the group A and 69,36% for the group B. There was no statistically significant difference between the average number of acne lesions before treatment between the two groups. The mean number of acne lesions after the treatment was significantly different (p<0,0001), 20% TCA peels showed superior results than 15% azelaic acid gel. Additionally, 96% of patients who underwent TCA peels were very satisfied with the results obtained.
Conclusions: TCA peel is an efficient and well tolerated method for the treatment of acne vulgaris.