Category Archives: AMM 2012, Volume 58, Number 5

Myocardial Protection with Sevoflurane in Patients with Cardiac Risk Undergoing Non-cardiac Surgery

Manolescu R1, Duțu M1, Negoiță S1, Popescu M2, Calu V3, Corneci D1, Azamfirei L4

1 Anaesthesia and Intensive Care Clinic, Elias University Emergency Hospital, Bucharest, Romania
2 Cardiology Clinic, Elias University Emergency Hospital, Bucharest, Romania
3 Surgery Clinic, Elias University Emergency Hospital, Bucharest, Romania
4 Anaesthesia and Intensive Care Clinic, County Emergency Clinical Hospital, Tîrgu Mureș, Romaina

Objective: Evaluation of cardioprotective effects of sevoflurane compared with propofol in high-risk cardiac patients undergoing non-cardiac surgery.
Material and methods: Prospective study enrolling 14 patients with cardiac risk Lee’s score > 3 points, undergoing abdominal elective surgery. The patients were divided into two groups: Group S (sevoflurane) – 8 patients who received balanced anesthesia with sevoflurane; Group P (propofol) – 6 patients receiving total intravenous anesthesia – target control infusion (TIVA-TCI). All patients were monitored hemodynamically, cardiac biomarkers (troponine I – TnI, the precursor of brain natriuretic peptide – proBNP, myocardial creatine kinase – CKMB) and inflammatory tests (high sensitive C-reactive protein – CRP, fibrinogen – FBG, interleukin 6 – IL6) were registered perioperatively.
Results: All patients had a decrease of mean arterial pressure (MAP) after induction, with significant values in Group P (48.4±3.82 mmHg). There were no acute cardiac perioperative events and the concentration of TnI after surgery was significantly lower in patients with sevoflurane anesthesia ( 0.017±0.01 ng/ml vs. 0.2±0.18 ng/ml) at 12 h and 24 h respectively (p <0.05). CKMB had lower postoperative values in Group S vs. Group P. ProBNP was elevated preoperatively in all patients and it is correlated with increased cardiac risk. In postoperative period the patients have lower levels in Group S compared with Group P (p <0.05). IL6 showed a significant decrease in patients in Group P at 12–48 h after surgery.
Conclusion: Anesthesia with sevoflurane, in patients with increased cardiac risk undergoing non-cardiac surgery, was accompanied by decreased values of TnI, proBNP and CKMB postoperatively, compared with propofol anesthesia.

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Four Years Experience in Retinopathy of Prematurity

Maki Cristina¹, Rusu Monica-Blanka¹, Moldovan M², Baghiu Maria Despina³

1 Department of Ophthalmology, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
2 Department of Biophysics, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Department of Paediatrics, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Purpose: Analysis of the results of screening and treatment for retinopathy of prematurity (ROP) in a sample of prematurely born babies evaluated in the Neonatal Intensive Care Unit and Neonatology Prematures Clinic of Targu Mures, between January 2008 and January 2012.
Material and method: We conducted a prospective study on all premature infants born with less than 34 weeks gestational age (GA) and lower than 2000 g birth weight (BW). The first ophthalmoscopic examination was performed between 4 and 6 weeks after birth, regardless of gestational age. The treatment was needed in threshold (or prethreshold) disease.
Results: Different stages of ROP were found in 24.1% from the total 503 infants: stage 1 in 34 eyes (28.1%), stage 2 in 65 eyes (53.7%), stage 3 in 16 eyes (13.2%) and stage 5 in 6 eyes (5%). We didn’t have cases with stage 4 ROP. Statistical analysis showed that GA and BW are highly significant risk factors for the development of ROP, with a risk reduction as the values of gestational age and birth weight were higher. The indication for laser treatment was set at 3.97% of all premature, respectively in 16.53% of children with ROP. Favorable evolution after laser treatment was observed in 80% of cases. From the others, who had no positive response to laser treatment, 75% had aggressive posterior ROP (APROP). We recorded a statistically significant association between BW and the incidence of cases which required laser therapy (p=0.0058), but no statistically association was found between GA and grades of diseases that needed laser (p=0.0789).
Conclusions: Screening for retinopathy of prematurity requires an experienced paediatrician-ophthalmologist, recognition of severe disease that requires treatment being crucial. Performed strictly and in accordance with international protocols, screening remains the first step in the detection and management of retinopathy of prematurity.

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Development of a Dissolution Method for Modified Release Tablets Containing an Insoluble Active Substance

Kelemen Éva Katalin1, Kelemen LJ1, Gyéresi Á2, Imre Silvia3, Obreja Mona1

1 Gedeon Richter Romania S.A., Tîrgu Mureș, Romania
2 Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Department of Analytical Chemistry and Drug Control, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objective: The aim of the present work is to develop a discriminative dissolution method for a practically insoluble pharmaceutical active substance such as indapamide.
Methods: Dissolution testing was performed in compliance with USP, using USP apparatus 2. The proper dissolution medium and the optimal rotation per minutes of the apparatus were optimized. In order to quantify the dissolution of indapamide from modified release tablets, a high liquid chromatographic method was developed and validated.
Results: An HPLC method was developed in order to provide adequate specificity trying several column types and different mobile phases. We selected the proper dissolution medium based on indapamide solubility, we determined the optimal speed of rotation of the dissolution tester for the indapamide in the selected medium, then we proved the discriminating power of the developed dissolution method.
Conclusions: A robust and discriminating HPLC method for analyzing dissolution samples containing indapamide was developed and successfully validated.

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Benzene Determination in Soft Drinks

Fülöp Ibolya, Pădureanu Anca, Kincses Ajtay Mária, Croitoru MD

Department of Toxicology, Biopharmacy and Pharmacokinetics, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objectives: Benzene is a known human carcinogen. We are exposed to benzene mainly through inhalation and a lesser extent through the ingestion of food and water. Benzene is formed in beverages when ascorbic acid coexists with benzoate salts. Certain additional conditions (heat, UV light, metallic ions) are required for detectable levels of benzene to be formed. The aim of this study was to investigate soft drinks for the presence of benzene.
Methods: A GC method was developed to identify and quantify benzene in beverages. Fifteen samples containing benzoate sodium and ascorbic acid were analyzed.
Results: The benzene concentration ranged between the limit of quantification and 8.81 µg/l. The EU guideline limits the benzene concentration at 1 µg/l in drinking water; 6 of the products tested were above this admitted level.
Conclusion: Based on the presented data, the safety of benzene as a preservative agent should be reconsidered.

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Quality of Life in Elderly Patients with Cluster C Personality Disorder

Echim Iulia1, Nireştean A1,2

1 Psychiatric Clinic No II, Tîrgu Mureş, Romania
2 University of Medicine and Pharmacy, Tîrgu Mureş, Romania

Introduction: Epidemiological studies have found reduced health-related quality of life (QoL) in patients with personality disorders (PDs), but few clinical studies have examined QoL in elderly patients with cluster C PDs. Our objective was to evaluate QoL in elderly patients with cluster C PDs admitted to the Psychiatric Clinic No II Tîrgu Mureș in all four domains related to QoL: physical health, psychological health, social relationships and environment.
Material and method: Elderly patients with cluster C PDs filled in the World Health Organization Quality of life (WHOQoL-Bref). An independent psychiatrist diagnosed cluster C PDs and Axis-I disorders by structured interviews (SCID II) and rated the Global Assessment of Functioning (GAF).
Results: Cluster C PD patients showed high co-morbidity with Axis I mental disorders, and they scored significantly lower on all the WHOQol dimensions. The WHOQoL physical health and social functioning were significantly associated with the GAF.
Conclusions: Elderly people with a cluster C PD have globally poor QoL and were more vulnerable to late-life distress, especially those with more than one diagnosis. In keeping with the results, widowhood, divorce hood, and living alone appear to be variables able to negatively influence QoL in this population.

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In Vitro Proof of Antiproliferative Effect of Soy Total Extract Via Mytochondrial Dehidrogenase Activity

Danciu (Țiulea) Corina1, Peev Camelia1, Feflea Ștefana1, Dehelean Cristina2, Motoc A3

1 Department of Pharmacognosy, Faculty of Pharmacy, Victor Babeș University of Medicine and Pharmacy, Timișoara, Romania
2 Department of Toxicology, Faculty of Pharmacy, Victor Babeș University of Medicine and Pharmacy, Timișoara, Romania
3 Department of Anatomy, Faculty of Medicine, Victor Babeș University of Medicine and Pharmacy, Timișoara, Romania

Introduction: Soy, Glycine max, Fam. Fabaceae is a species of vegetables originary from East Asia. The vegetal product used both in the pharmaceutical and nutritional area are the beans, Sojae semen. Vegetable soybean is rich in phytochemicals beneficial to the human being and is therefore considered a nutraceutical or a functional food crop. The aim of this study is to test the antiproliferative effect of soy total extract, employing different concentrations, on B164A5 murinic melanoma cell line, using the MTT proliferation assay.
Material and method: Soybean seeds were grounded and a solvent formed of DMSO-ethanol-water in 5-70-25 v/v/v ratio was prepared. The extraction was made at room temperature using an ultrasonic bath (Falc LCD Series) for 30 minutes, 59 kHz. The solvent was evaporated with a rotary evaporator at 50ºC. B164A5 cells were incubated 24 h with 100 µM, 50 µM, 30 µM, 15 µM, 1 µM, 0 µM soy total extract. Results: MTT analysis showed an inhibition of all chosen concentrations of soy total extract. The inhibition was directly proportional with the concentration of soy total extract. Additionally, a change in the number and morphology of B164A5 cells was noticed starting from the concentration of 15 µM.
Conclusion: Our results suggest that soy total extract presents an antiproliferative effect in vitro on B164A5 murinic melanoma cell line.

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Obesity and Metabolic Syndrome as Risk Factors of Colorectal Polyps and Colorectal Cancer

Crosnoi Daniela1, Bățagă Simona2, Macarie Melania2, Chindriș V3

1 County Emergency Clinical Hospital, Tîrgu Mureș, Romania
2 Gastroenterology Clinic 1, Faculty of Medicine, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Nova Vita Hospital, Tîrgu Mureș, Romania

Purpose: Obesity and metabolic syndrome, each represent one of the risk factors in colon cancer and colon polyps. We have studied the association between obesity, metabolic syndrome and the risk of developing colorectal cancer and colorectal polyps.
Materials and methods: Our study refers to patients with mucosal modifications at the level of the colon, hospitalized and investigated through colonoscopy in the Gastroenterology Clinic 1, Tîrgu Mureș between 2008–2011.
Results: There were 324 patients with colorectal cancer and colorectal polyps, compared with 345 control patients investigated in the same hospital. In the study group, 69 patients (21.29%) were overweight (BMI 25–29.99 kg/m2) and 71 patients (30.90%) were obese (BMI> 30 kg/m2), compared with the control group, where 53 patients (15.36%) were overweight and 32 patients (9.26%) were obese. There was a significant association between obesity and risk for colorectal cancer and colorectal polyps: BMI >30 kg/m2 – OR = 2.89, CI: 1.64–5.10. We also observed a significant increase in the risk for colorectal polyps and colorectal cancer in parallel with the increase of the number of metabolic syndrome components: 1 component – OR = 1.55, CI: 1.09–2.20; 2 components OR = 2.42, CI: 1.54–3.81; 3 components OR = 2.37, CI: 1.16–4.81; 4 or more components OR = 5.27, CI: 1.07–25.85.
Conclusions: The results of our study showed that obesity and metabolic syndrome are associated with an increased risk for the development of colorectal polyps and colorectal cancer.

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Presence of Nitrite and Nitrate Anions in Precipitation in Tîrgu Mureş and Surrounding Areas as a Result of Nitric Oxide Pollution

Croitoru MD, Szabó Zs, Kincses Ajtay Mária, Fülöp Ibolya

Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objective: The city of Tîrgu Mureş, and of course other cities around the world, is polluted with nitrogen oxides. Most of the time, nitrogen oxides concentration into the air is between legal limits. However, this measurement is made on ground level and most of the pollutant gases are raised into the atmosphere from where is possible to return to the ground in form of nitrite and nitrate. These substances can contaminate soil and groundwater. The objective of the study was to measure nitrite and nitrate contents in groundwater and precipitation in and around Tîrgu Mureş.
Methods: A simple ion pair high pressure liquid chromatographic method with UV detection was used.
Results: High amounts of nitrite and nitrate were measured up to 25 km from the city of Tîrgu Mureş. An astonishing 4200 mg/ml melted snow was measured at about 100 m from the polluting plant. Other concentrations were between tens and hundreds of μg/ml melted snow. Rain water concentrations were in the same range. Most of the spring water samples we tested were over the drinking water limits stated by EU.
Conclusions: The high amounts of nitrites and nitrates found in precipitations around the city of Tîrgu Mureş show that pollution with nitrogen oxides goes beyond expected extent. This pollution is a health risk since precipitation will contaminate soil, and possibly crops will be contaminated too. Presence of airborne free radicals and activated pollutants will also increase due to the presence of these anions in unusual high amounts in air moisture.

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Researches Upon Indigenous Herbal Products for Therapeutic Valorification in Metabolic Diseases.Note I. Polyphenols’ Analysis of Rubi idaei folium

Costea Teodora, Istudor Viorica, Nencu Ioana

Department of Pharmacognosy, Phytochemistry, Phytotherapy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Introduction: Raspberry leaves (Rubi idaei folium) are a source of flavonoids, gallic tannins, phenolcarboxylic acids, sterols, vitamin C and oligoelements (selenium, vanadium). The leaves are not mentioned by the scientific literature for their possible use in metabolic diseases (diabetes, dyslipidaemia, hyperuricaemia), but among their compounds, polyphenols, sterols and vitamin C might be responsible for these properties. The aim of the study was to determine the optimum time for harvesting the leaves, in order to obtain pharmacological active extracts, with the highest content of flavonoids, phenolcarboxylic acids and tannins.
Material and methods: Qualitative (specific chemical reactions and thin layer chromatography, TLC) and quantitative (spectrophotometric methods and high liquid chromatography, HPLC) analyses upon leaves, harvested at different stages of development (before and after blossom, at fruits’ ripening and at the end of vegetative state) were applied.
Results: Flavonoids, tannins and phenolcarboxylic acids were present in all vegetative states; rutin, hyperoside and chlorogenic acid were identified using TLC. The greatest amount of total polyphenols (16.0317 g% tannic acid), tannins (11.4376 g% tannic acid), flavonoids (2.6347 g% hyperoside) and phenolcarboxylic acids (2.4011 g% chlorogenic acid) were found in young leaves. Using HPLC, gallic, chlorogenic, caffeic, p-coumaric and ferulic acids, tannin, rutin, quercetin and catechin were identified in young leaves; rutin (0.0540 g%) and p-coumaric acid (0.03174 g%) were also quantified.
Conclusions: The highest content of flavonoids, phenolcarboxylic acids and tannins were found in leaves, harvested before blossom. The tannins content were higher, compared with scientific literature.

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Genetic Polymorphism of GSTP1 Gene and Lung Cancer Risk in Northern Romania

Cătană Andreea1, Popp RA1, Pop Monica2, Porojan MD3, Petrișor Felicia1, Fărcaș M1, Pop IV1

1 Department of Molecular Sciences, University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Medical Specialities, University of Medicine and Pharmacy, Cluj-Napoca, Romania
3 Department of Internal Medicine, University of Medicine and Pharmacy, Cluj-Napoca, Romania

Background: Glutathione S transferase P1 – an important member of the xenobiotic encoding enzymes, might contribute to the variability in individual susceptibility to lung cancer and may be important in exposure to carcinogens and therefore lung cancer development in smokers.
Objectives: This is a cross-sectional, randomized, case-control study for the evaluation of the frequency of GSTP1 alleles among patients with lung cancer.
Subjects and methods: The study included 108 cases of lung cancer diagnosed patients (histopathological examination), and 123 healthy unrelated controls. GSTP1 genotyping was carried out using PCR amplification of relevant gene fragment, followed by restriction enzyme digestion. Detection of GSTP1 alleles was determined by analysis of resulting restriction fragment length polymorphism (RFLP), followed by gel electrophoresis.
Results: Molecular analysis revealed an increased frequency of GSTP1 mutant genotype in the study group compared to the control group (X2 = 0.133, p = 0.049, OR = 1.726, CI = 1–2.977). It appears that the effect of the GSTP1 mutant allele may vary according to histological subtype. The polymorphic I105V allele of GSTP1 gene was associated with an increased risk of lung adenocarcinoma.
Conclusions: GSTP1 polymorphism may be associated with increased risk to lung cancer and the homozygous Ile105Val genotype was found at a significantly higher frequency in the adenocarcinoma group.

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