REVIEW_ARTICLE Kojic acid-derived tyrosinase inhibitors: synthesis and bioactivity Tyrosinase is a key enzyme for melanin biosynthesis, catalyzing the oxidation of L-tyrosine to L-dopaquinone. The tyrosinase inhibition is an effective approach to control hyperpigmentation in human skin and enzymatic browning in fruits and vegetables. Kojic acid is a naturally-occurring tyrosinase inhibitor which has been clinically used to treat the hyperpigmentation of skin. However, kojic acid as a hydrophilic small-molecule has insufficient inhibitory activity and stability, with considerable toxicity. To overcome these drawbacks, synthetic derivatives of kojic acid were developed, which exhibited enhanced tyrosinase inhibitory activity and more favorable stability relative to kojic acid. In this context, the synthesis and biological activity of kojic acid derivatives as tyrosinase inhibitors have been highlighted. http://pbr.mazums.ac.ir/article-1-21-en.pdf 2015-01-19 1 17 10.18869/acadpub.pbr.1.1.1 Kojic acid 4H-pyran-4-one derivatives enzyme inhibitors structural modifications Seyedeh Mahdieh Hashemi 1 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Saeed Emami 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR
ORIGINAL_ARTICLE Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M) as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios.  Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets. http://pbr.mazums.ac.ir/article-1-22-en.pdf 2015-01-19 18 25 10.18869/acadpub.pbr.1.1.18 Ocimum basilicum mucilage release HPMC swelling erosion Majid Saeedi 1 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Katayoun Morteza-Semnani 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. AUTHOR Jafar Akbari 3 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Mohammad Hossein Bazargani 4 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Gholamreza Amin 5 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, AUTHOR
ORIGINAL_ARTICLE Chemoprotective effect of thymol against genotoxicity induced by bleomycin in human lymphocytes Bleomycin (BLM) as an anti-cancer agent causes tissue toxicities through DNA damaging and cell deaths. The aim of this study was to investigate the effects of thymol against genotoxicity and anti-proliferation induced by BLM in normal human lymphocytes and ovarian cancer cells. Peripheral blood samples were collected from human volunteers and were incubated with thymol at different concentrations at 50, 100, and 150 μM. After 2 h incubation, the whole blood was treated with BLM. Then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. Human ovarian cancer cells (SKOV-3) were treated with thymol at various concentrations and/or BLM with their combinations and then cell viability were evaluated. Incubation of whole blood with thymol exhibited a significant decrease in the incidence of micronuclei in lymphocytes caused by BLM, as compared with similarly BLM-treated lymphocytes without thymol. Neither enhanced cell death nor cell protective effect was observed using thymol pre-treatment of SKOV-3 cells. This study showed that thymol selectively protects human lymphocytes against DNA damage induced by BLM without any protection on cancer cell. This result is promising for using this natural product in treatment of ovarian cancer with BLM. http://pbr.mazums.ac.ir/article-1-23-en.pdf 2015-01-19 26 31 10.18869/acadpub.pbr.1.1.26 Bleomycin genotoxicity thymol micronuclei anti-proliferation Hojat-Allah Arab 1 Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Mahdieh Fathi 2 Research Student Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Elahe Mortezai 3 Research Student Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Seyed Jalal Hosseinimehr 4 Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR
ORIGINAL_ARTICLE Demographic and clinical characteristics of gastric cancer patients in north of Iran, Mazandaran province, 2008-2014 Gastric cancer has been known as a poor prognosis disease with a high degree of mortality. In Iran, it has been increased during the previous two decades, especially in northern part of the country. The aim of this study was to determine the demographic and clinical characteristics of gastric cancer in Mazandaran province. All patients with gastric cancer diagnosis treated in the Imam Khomeini educational hospital or Touba Polyclinic, a university affiliated center, from March 2008 to March 2014 were included. Demographic data, the symptoms at the time of presentation, tumor size, type of tumor, lymph node involvement, status in terms of metastatic disease, therapeutic plan and type of chemotherapy regimens were gathered from patients’ medical records. Statistical analysis was performed using SPSS, version 16. Totally, 643 patients were investigated. The mean age of patients was 64.34 years and men were more affected than women. “Time to relapse” and “time to progression” were 13 and 6.5 months, respectively. The most common initial symptoms at diagnosis were nausea, vomiting and epigastric pain (47.4%). Only in 6.3%, the disease was diagnosed at the initial stages. The most common site of involvement was cardia (almost 40%) and antrum (32%). More than 91% of tumors were adenocarcinoma. DCF (Docetaxel, Cisplatin, 5FU) (43.3%), Xeloda (15.2%), DOX (Docetaxel, Oxaliplatin) (13.8%) and ECF (Epirubicin, Cisplatin.5FU) (9.2%) were the most common used regimens. There was a trend for improved survival with DCF regimen (P = 0.08). Most gastric cancer patients were referred in the advanced stage or metastatic disease. The demographic characteristics are consistent with other previous reports. DCF regimen may have some advantages over other chemotherapy regimens. http://pbr.mazums.ac.ir/article-1-24-en.pdf 2015-01-19 32 36 10.18869/acadpub.pbr.1.1.32 Gastric Cancer Demographic Chemotherapy DCF Mazandaran Seyed Khalil Mousavi 1 Students Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Sari. Iran. AUTHOR Ghasem Janbabai 2 Department of Hematology and Oncology, Cancer Research Center, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Bizhan Kouchaki 3 Students Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Sari. Iran AUTHOR Hanieh Borhani 4 Cancer Research Center, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Masoumeh Rashidi 5 Cancer Research Center, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Ebrahim Salehifar 6 Department of Clinical Pharmacy, Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR
ORIGINAL_ARTICLE Antioxidant properties of Helichrysum pseudoplicatum Nab The genus Helichrysum (Asteraceae) is comprised of approximately 500-600 species and used for the treatment of a variety of pathological conditions in folk medicine in many countries. In this study, antioxidant activities of aerial parts of H. pseudoplicatum were investigated employing various in vitro assay systems, i.e. 2,2-diphenyl-1-picrylhydrazyl (DPPH)  and nitric oxide radical scavenging, reducing power and hydrogen peroxide scavenging. IC50 for DPPH radical-scavenging activity was 438.9 ± 15.6 µg/ml. The extract exhibited good reducing power at 25 - 400 µg/ml but was not comparable with that of vitamin C. The extract showed good nitric oxide-scavenging activity. IC50 was 474.3 ± 11.8 µg/ml. It was capable of scavenging hydrogen peroxide in a concentration dependent manner. It showed good activity. Its IC50 was 159.8 ± 8.2 µg/ml. The IC50 values for ascorbic acid and BHA were 21.4 and 52.0 µg/ml, respectively. The total amount of phenolic compounds in the extract was determined as gallic acid equivalents (22.7 ± 3.1 mg/g of extract) and total flavonoid contents were calculated as quercetin equivalents (9.6 ± 1.3 mg/g of extract) from a calibration curve. This plant contained low amount of total flavonoids and phenolic compounds. Its moderate antioxidant activities may be attributed to its low levels of phenols and flavonoids. http://pbr.mazums.ac.ir/article-1-25-en.pdf 2015-01-20 37 43 10.18869/acadpub.pbr.1.1.37 Antioxidant activity Helichrysum pseudoplicatum Radical scavenging Reducing power Mohammad Ali Ebrahimzadeh 1 Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. AUTHOR Afsaneh Tavassoli 2 Research Center of Natural Resources of Mazandaran, Sari, Iran. AUTHOR
ORIGINAL_ARTICLE Copper and selenium levels in women with second-trimester induced abortion in Mazandaran, 2009: A case control study Abortion is the termination of a pregnancy by the removal or expulsion of a fetus or embryo from the uterus, resulting in or caused by its death. Missed abortion is the most common dangerous condition in pregnancy. An abortion can occur due to maternal complications, chronic disease, endocrine disorders, abortificient drugs, radiation, heavy metals and toxins. The study population consisted of 43 aborted patients and 43 normal pregnant females, referred to Imam Khomeini hospital. 10 mL blood was taken and centrifuged to isolate the patients’ serum. Then, the samples were analyzed to determine the copper and selenium levels, using atomic absorption spectrometry. All data were statistically analyzed by T-test and Mann-Whitney methods. As a result, we found a significant decrease in serum copper level in cases compared with controls. Also the results showed an insignificant decrease in serum selenium levels in the patients compared to the healthy women. According to the results, deficiency of the essential heavy metals may be a probable reason for missed abortion occurrence. These deficiencies can be related to malnutrition, decreased consumption of essential metals and supplementary compounds in pregnancy, lack of regular laboratory monitoring. Thus, consuming supplements in Iranian pregnant women can be helpful in completing a successful pregnancy. http://pbr.mazums.ac.ir/article-1-26-en.pdf 2015-01-20 44 47 10.18869/acadpub.pbr.1.1.44 Abortion copper selenium serum concentration Zoleikha Atarod 1 Department of Gynecology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Nima Emadi 2 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Seyed Soheil Saeedi Saravi 3 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences; Tehran, Iran AUTHOR Mona Modanlookordi 4 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Mohammad Shokrzadeh 5 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences; Mazandaran, Pharmaceutical Research Center, Sari, Iran AUTHOR
ORIGINAL_ARTICLE The protective effect of Sambucus ebulus against lung toxicity induced by gamma irradiation in mice The aim of present study was to investigate the potential antioxidant and lung protective activities of Sambucus ebulus (SE) against toxicity induced by gamma irradiation. Hydroalcoholic extract of SE (20, 50 and 100 mg/kg) was studied for its lung protective activity. Phenol and flavonoid contents of SE were determined. Male C57 mice were divided into ten groups with five mice per group. Only the first and second groups (as negative control) received intraperitoneally normal saline fluid. Groups 3 to 5 received only SE extract at doses of 20 mg/kg, 50 mg/kg and 100 mg/kg intraperitoneally; three groups were repeatedly injected for 15 days as chronic group. Groups 6 to 8 received a single-dose of gamma irradiation just 2 hours before irradiation as acute group. The ninth and tenth groups (as positive control) received only gamma rays. Animal was exposed whole-body to 6 Gy gamma radiation. After irradiation, tissue sections of lung parenchyma were examined by light microscope for any histopathologic changes. SE at doses 50 and 100 mg/kg improved markedly histopathological changes induced by gamma irradiation in lung. Lung protective effect of SE could be due to attention of lipid peroxidation. Our study demonstrated that SE as a natural product has a protective effect against lung toxicity induced by   gamma irradiation in animal. http://pbr.mazums.ac.ir/article-1-27-en.pdf 2015-01-24 48 54 10.18869/acadpub.pbr.1.1.48 Sambucus ebulusi Gamma irradiation Histopathology changes Antioxidant Lung Protective Mohammad Karami 1 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Seyed Sajad Ale-Nabi 2 Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Anahita Nosrati 3 Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Atefeh Naimifar 4 Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR
ORIGINAL_ARTICLE Assessment of mortality rate and its relation to off-hours and holidays in patients admitted to the CCU of a Noor general hospital Despite the reduction of mortality rate in the past years, coronary artery diseases (CADs) are the main reason of death in the world. Many factors including changes in nurses and medical staffs, numbers of beds influence the mortality rate of patients admitted in holidays and night time. The objectives of this study were to clarify the association between mortality rate and off-hours and holidays in patients admitted to the cardiac care unit (CCU) of Noor General Hospital. This is a retrospective study of 186 hospitalized patients in CCU that suffered cardiac arrest during 10 years. Patients 'data was gathered in a questionnaire including information about sex, date and cause of hospitalization and cardiac arrest, CPR duration, admission in working hours, off-hours and holidays. Data showed that patients were between the ages of 21 to 88 years old (66.92 ± 52.12), and 92 patients (50%) were female. Time of admission of 146 deceased patients (79.5%) and time of CPR of 145 of them (78.9%) were in off- hours and holidays. Patients who had died of pulmonary embolism were admitted in the evenings and holidays. Cardiac arrest and CPR of hospitalized patients diagnosed with cardiogenic shock and chronic renal failure were in the evening shift and holidays, too. Higher mortality of CCU patients  admitted during nights, evening hours, and holidays or when CPR were performed on them during these times  showed that patient care and diagnostic and treating procedures were not performed effectively; and this issue could be  due to the fewer number of physicians, nurses or fatigue of staffs at night hours. http://pbr.mazums.ac.ir/article-1-28-en.pdf 2015-01-31 55 62 10.18869/acadpub.pbr.1.1.55 Mortality CCU holidays off- hours CPR Shahram Ala 1 Department of Clinical Pharmacy. Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Abbas Alipour 2 Thalassemia Research Center, Department of Community Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Fatemeh Faramarzi 3 Department of Clinical Pharmacy. Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran AUTHOR Khadijeh Farkhondeh 4 Imam Khomeini General Hospital, Mazandaran province, Noor, Iran AUTHOR