Drug Applied Research Center

Tabrīz, Iran

Drug Applied Research Center

Tabrīz, Iran
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Akbarzadeh A.,Drug Applied Research Center | Zarghami N.,Tabriz University of Medical Sciences | Mohammad R.,Tabriz University of Medical Sciences | Barkhordari A.,Tabriz University of Medical Sciences
International Journal of Nanomedicine | Year: 2012

Background: Superparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxo-rubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet. Methods: A series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG 2000, PEG 3000, and PEG 4000) as an initiator. The bulk properties of these c opolymers were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry. Results: The doxorubicin encapsulation amount was reduced for PLGA:PEG 2000 and PLGA:PEG 3000 triblock copolymers, but increased to a great extent for PLGA:PEG 4000 triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe 3O 4 magnetic nanoparticles modifed with PLGA:PEG 2000, PLGA:PEG 3000, and PLGA:PEG 4000 copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe 3O 4-PLGA:PEG 4000 magnetic nanoparticles had no cytotoxicity and were biocompatible. Conclusion: There is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer. © 2012 Akbarzadeh et al.


Entezariasl M.,Ardebil University of Medical science | Khoshbaten M.,Drug Applied Research Center | Isazadehfar K.,Ardebil University of Medical science | Akhavanakbari G.,Ardebil University of Medical science
Eastern Mediterranean Health Journal | Year: 2010

Postoperative nausea and vomiting are common complications of anaesthesia. This double-blind clinical trial assessed the incidence of nausea and vomiting after cataract surgery with intravenous anaesthesia in 100 patients randomly assigned to preinduction placebo (saline), metoclopramide (10 mg), dexamethasone (8 mg) or the 2 drugs combined. The incidence of nausea in the recovery room was 44% with placebo, 20% with metoclopramide, 16% with dexamethasone and 8% with the combination. The incidence of vomiting was 20%, 4%, 4% and 0% respectively in the 4 groups. Metoclopramide plus dexamethasone combination significantly decreased nausea and vomiting both in the recovery room and 24 hours afterwards and is recommended for high-risk groups, especially in outpatient surgeries.


PubMed | Tabriz University of Medical Sciences, Islamic Azad University at Tabriz, Shahid Beheshti University of Medical Sciences and Drug Applied Research Center
Type: Journal Article | Journal: Journal of dental research, dental clinics, dental prospects | Year: 2014

Background and aims. The aim of the present study was to compare the inhibitory effects of two systemic doses of HESA-A on prevention of 4-NQO-induced tongue neoplasms in rats. This study evaluated weight and histopathological changes. Materials and methods. Forty-eight male Sprague Dawley rats were divided into four groups of A, B, C and D of each 12 rats. The rats in groups B to D received 30 ppm of 4-Nitroquinoline-1-oxide (4-NQO) in drinking water for 12 weeks. When feeding with 4-NQO was initiated, the rats in groups B and C received HESA-A at doses of 250 and 500 mg/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. Results. The mean body weights of rats in groups B, C and D were significantly lower than that in group A (P < 0.05). There were no significant differences in weight changes between groups B, C and D. In the present study, after 12 weeks of treatment, Tongue specimens in groups B and C did not exhibit severe dysplastic changes; however, concurrent hyperplasia, without atypia and mild-to-moderate dysplastic changes were detected. These changes were significantly less than those in group D, with significant differences between group D and groups A, B and C (P<0.001, P<0.01 and P<0.05, respectively). Conclusion. HESA-A has dose-dependent inhibitory effects on the development of neoplasms of the tongue.


Nayebi A.M.,Drug Applied Research Center | Nayebi A.M.,Tabriz University of Medical Sciences | Rad S.R.,Islamic Azad University at Tehran | Saberian M.,Tabriz University of Medical Sciences | And 2 more authors.
Pharmacological Reports | Year: 2010

Receptors for 5-HT1A are widely distributed throughout the basal ganglia, and their activation results in an inhibition of dopamine (DA) release. This study aimed to investigate the effect of buspirone, as a partial agonist of 5-HT1A receptors, on 6-hydroxydopamine (6-OHDA)-induced catalepsy in male Wistar rats. Catalepsy was induced by unilateral infusion of 6-OH-DA (6 μg/ 2 μl/rat) into the central region of the substantia nigra pars compacta (SNc) and assayed by the bar-test method 60, 120 and 180 min after drug administration. The results demonstrated that intraperitoneal (ip) injection of buspirone at doses of 5, 7.5 and 10 mg/kg decreased catalepsy compared with the control group. In addition, intra-SNc injection of 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT; 10 μg/rat), a 5-HT1A receptor agonist, decreased 6-OHDA induced catalepsy. The effects of buspirone (7.5 mg/kg, ip) and 8-OH-DPAT (10 μg/rat, intra-SNc) were abolished by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydro-bromide (NAN-190; 10 μg/rat, intra-SNc), a 5-HT1A receptor antagonist. Our study indicates that buspirone improves catalepsy in a 6-OHDA-induced animal model of Parkinson's disease through activation of nigral 5-HT1Areceptors. However, further investigations should be undertaken to clarify the exact mechanism of interaction between 5-HT1A and DA receptors. © 2010 by Institute of Pharmacology Polish Academy of Sciences.


PubMed | Tabriz University of Medical Sciences, Drug Applied Research Center and Nutrition Research Center
Type: | Journal: Laboratory medicine | Year: 2016

To investigate the association of uncoupling protein-2 (UCP2) -866G>A gene polymorphism (rs659366) with nonalcoholic fatty liver disease (NAFLD).We performed a case-control study with a cohort of 75 patients with NAFLD (of Iranian ethnicity) and 76 healthy individuals of Iranian ethnicity. The UCP2 -866G>A polymorphism (rs659366) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Patients with AA and AG genotypes were 71% and 68%, respectively, more likely to have NAFLD, compared with individuals with the GG genotype (reference group). In subjects with a GG genotype, serum triglyceride (TG) concentration was significantly higher in patients with NAFLD (P=.04). Serum alanine aminotransferase (ALT) concentrations in all 3 genotypes and serum aspartate aminotransferase (AST) concentrations in AG and GG genotypes of UCP2 gene polymorphism were significantly higher in patients (P <.05).Our results revealed a modest modifier effect of -866G>A UCP2 polymorphism in patients with NAFLD.


Baharivand N.,Nikookari Eye Hospital | Zarghami N.,Drug Applied Research Center | Panahi F.,Tabriz University of Medical Sciences | Yazdan Dokht Ghafari M.,Tabriz University of Medical Sciences | And 2 more authors.
Clinical Ophthalmology | Year: 2012

Background: Diabetic retinopathy is a serious microvascular disorder of the retina. Vascular endothelial growth factor (VEGF) expression, induced by high glucose levels and hypoxia, is a main feature in retinopathy. The aim of this study was to evaluate the relationship between vitreous and serum VEGF levels and control of diabetes and microalbuminuria in patients with proliferative diabetic retinopathy. Methods: Sixty-five patients were enrolled in this case-control study, comprising 30 patients with proliferative diabetic retinopathy (cases) and 35 patients with nonproliferative diabetic retinopathy (controls). The vitreous VEGF level was compared with the serum VEGF level in both groups. Glycosylated hemoglobin (HbA 1c), microalbuminuria, serum creatinine, and stage of nephropathy and retinopathy were also measured in patients with proliferative diabetic retinopathy, and the relationship between these parameters and serum and vitreous VEGF levels was investigated. Results: Mean vitreous and serum VEGF levels were significantly higher in cases compared with controls (P = 0.001, P = 0.011, respectively). There was also a significant correlation between vitreous and serum VEGF levels (P = 0.012, r = 0.453). VEGF levels in patients with well controlled blood glucose (P = 0.039), on drug treatment (P = 0.045) and at an early stage of nephropathy (P = 0.042) were significantly lower. There was a significant correlation between VEGF and albumin to creatinine ratio (P = 0.017, r = 0.432). Conclusion: Serum and vitreous VEGF levels was significantly lower in patients on oral therapy, in those with well controlled glycemia, and in those with early-stage retinopathy. Administration of anti-VEGF had a good effect in reducing the progression of proliferative diabetic retinopathy. © 2012 Baharivand et al, publisher and licensee Dove Medical Press Ltd.


Abbasi M.M.,Drug Applied Research Center | Abbasi M.M.,Student Research Committee | Khiavi M.M.,Tehran University of Medical Sciences | Monfaredan A.,Islamic Azad University at Tabriz | And 4 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1- oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOXMTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.


Hosseinlou A.,Urmia University of Medical Sciences | Khamnei S.,Drug Applied Research Center | Zamanlu M.,Tabriz University of Medical Sciences
International Journal of Clinical and Experimental Medicine | Year: 2014

Studies have shown that dehydrated humans or animals in a warm environment begin to sweat within seconds to minutes after drinking. This phenomenon is one of the drinking-induced thermoregulatory responses; being investigated from different aspects. Our objective is to show the difference of voluntary drinking and imposed drinking in the methodology of these experiments. Six healthy subjects 23.7 ± 0.6 yr old and 80.7 ± 5.7 kg wt were dehydrated by performing mild exercise (ergometer cycling) in a hot and humid chamber (38-40°C, 20-28% relative humidity). We incorporated two protocols: after dehydration, subjects were allowed to drink water with 1) imposed volumes of 1, 3, 5 ml/kg and 2) voluntary volumes; on four separate days. The sweating rate was measured on the forehead area before and after drinking. Sweating increased markedly just a few minutes after the onset of drinking. The mean sweat rates of the imposed volumes of 1, 3, 5 ml/Kg were 0.33 ± 0.15, 0.31 ± 0.17, 0.47 ± 0.21 respectively and for the voluntary volume it was 0.54 ± 0.19. The mean intake in the voluntary trial was 6.58 ± 1.14 ml/Kg, more than the imposed volume of 5 ml/Kg. The trend of the rate of the sweating response in the imposed trials was distinct from the response in the voluntary trial. Conclusion: There exists a difference between voluntary drinking and imposed drinking in the sweating response that follows rehydration. So it is suggested to use the methods of voluntary drinking in the investigations of this phenomenon, to reveal the natural events that happen in the actual circumstances. © 2014 E-Century Publishing Corporation. All rights reserved.


PubMed | Drug Applied Research Center
Type: Journal Article | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2014

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model.In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1- oxide induced OSCC.RESULTS showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX- MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05).Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.


PubMed | Drug Applied Research Center
Type: Journal Article | Journal: Asian Pacific journal of cancer prevention : APJCP | Year: 2015

Oral carcinoma (OC) remains as one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties on various human cancer cells, although the mechanisms of action remain to be addressed. This study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of p53 as a main prognosticator of OC.60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500 mg/kg body weight of Hesa-A three times a day. The two other groups considered as treated and untreated healthy groups. At the end of experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR.Our results indicated that compared to healthy group, p53 over expressed ~ 40% in untreated carcinoma group. After treatment with 250 mg/kg and 500 mg/kg body weights of Hesa-A , p53 level dropped by 53.4% and 13.6 %, respectively, compared to untreated carcinoma group (p<0.05, p<0.0001). Moreover, there was a significant relation between p53 mRNA content and observed pathological changes in studied groups (p<0.05).These data provide insights into the mechanism(s) by which Hesa-A improves clinical outcome of oral carcinoma by modulation of p53 expression.

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