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1.
Addict Health ; 15(2): 87-92, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37560396

RESUMO

Background: Opiate abuse has been critically increased in the world, especially in Iran. Owing to the association of opiate use with multiple human cancers and neurological disorders, seeking for genetic and epigenetic effects of opium can pave the way for early diagnosis of major health defects in addicted users. Accordingly, the present study aimed to determine the methylation status of the promoter of two genes, which are actively involved in neurodevelopment and cancer evolution. Methods: DNA was isolated from peripheral blood of 28 opium abusers and 19 healthy controls and then subjected to sonication. Sonicated DNAs undergone methylated DNA immunoprecipitation-real time polymerase chain reaction (MeDIP-Real Time PCR) using specific primer pairs designed for HOXA9 and NISCH genes. Obtained data were analyzed using SPSS software. Findings: HOXA9 and NISCH genes were found to be significantly methylated in addicted users compared to controls (P<0.001) which was significantly associated with the mean of the age regarding HOXA9 gene (P=0.002). Neither opium amount nor duration or route of using was associated with the methylation status of HOXA9 or NISCH genes. Conclusion: Hypermethylation of HOXA9 and NISCH genes as tumor suppressor in opium-addicted individuals can be considered as confirmatory evidence for carcinogenesis of opium. Further studies are required to figure out the role of epigenetic alterations in cancer evolution among opium users.

2.
Sci Rep ; 13(1): 7999, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198239

RESUMO

A practical technique was applied to fabricate CuO nanostructures for use as the electrocatalyst. The green synthesis of cupric oxide nanoparticles (CuO NPs) via co-precipitation is described in this paper using an aqueous extract of Origanum majorana as both reductant and stabilizer, accompanied by characterization via XRD, SEM, and FTIR. The XRD pattern revealed no impurities, whereas SEM revealed low agglomerated spherical particles. CuO nanoparticles and multi wall carbon nanotubes (MWCNTs) have been used to create a modified carbon paste electrode. Voltammetric methods were used to analyze Tramadol using CuONPs/MWCNT as a working electrode. The produced nanocomposite showed high selectivity for Tramadol analysis with peak potentials of ~ 230 mV and ~ 700 mV and Excellent linear calibration curves for Tramadol ranging from 0.08 to 500.0 µM with a correlation coefficient of 0.9997 and detection limits of 0.025. Also, the CuO NPs/MWCNT/CPE sensor shows an an appreciable sensitivity of 0.0773 µA/µM to tramadol. For the first time the B3LYP/LanL2DZ, quantum method was used to compute DFT to determine nanocomposites' connected energy and bandgap energy. Eventually, CuO NPs/CNT was shown to be effective in detecting Tramadol in actual samples, with a recovery rate ranging from 96 to 104.3%.


Assuntos
Nanocompostos , Nanotubos de Carbono , Tramadol , Nanotubos de Carbono/química , Nanocompostos/química , Eletrodos , Técnicas Eletroquímicas/métodos
3.
Heliyon ; 7(4): e06683, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33869871

RESUMO

Alzheimer's disease (AD), is among the most growing neurodegenerative diseases, which is mainly caused by the acetylcholine neurotransmitter loss in the hippocampus and cortex. Emerging of the dual Acetylcholinesterase (AChE)/Butyrylcholinesterase (BuChE) inhibitors has increased for treating Alzheimer disease. In this study, we would like to report the design and synthesis of a new sequence of 1-benzyl-4-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium derivatives (BOPs) assessed as BuChE and AChE inhibitors. Ellman's approach was used for the evaluation of AChE and BuChE inhibitory activities. Moreover, docking research was conducted to predict the action mechanism. Among all synthesized compounds, 1-(3-bromobenzyl)-3-((4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium bromide (BOP-1) was found to be the most active compound with dual activity for inhibition of AChE (IC50 = 5.90 ± 0.07µM), and BuChE (IC50 = 6.76 ± 0.04µM) and 1-(4-chlorobenzyl)-3-((6,7-dimethoxy-4-oxoquinazolin-3(4H)-yl)methyl) pyridin-1-ium chloride (BOP-8) showed the highest AChE inhibitory activity (IC50s = 1.11 ± 0.09 µM). The synthesized compounds BOP-1 and BOP-8 could be proposed as valuable lead compounds for further drug discovery development against AD.

4.
Traffic Inj Prev ; 22(3): 195-200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33709853

RESUMO

OBJECTIVE: Road traffic crashes are one of the global public health concerns and remain at high priority in many countries. Driving under the influence of drugs increases the risk of crashes through altering the driver's mental state and reactions. This study was conducted to determine the relationship between driving pattern and substance abuse among drivers in Kerman, a city in Iran, in order to enable policy makers to make the necessary decisions in planning and executing guidelines. METHODS: The population of this descriptive study was drivers involved in road traffic crashes admitted to the emergency department of Shahid Bahonar university hospital in summer 2019. After obtaining demographic information, type of vehicle, type of collision and pattern of serious injury, 222 eligible drivers were tested for tramadol, cannabis, amphetamine, methamphetamine, morphine and methadone using one step urine test strips. Chi-square test, Fisher's exact test, Whitney-Mann and Kruskal-Wallis tests and one-way Anova test was performed using SPSS version 22. RESULTS: The statistics showed that most drivers were male (90.5%), married (63.5%), age group (18-30) and had positive urine test (76.6%). In addition to uniqueness of dual-drug detection among male drivers (7.7%), the most common substances detected were methadone and morphine with 34.7% and 27.5% respectively. The most common injuries were lower limb and hip injuries mostly among motorcyclists. The results indicated that characteristics of being under 30's, married, school dropout, self-employed and motorcyclist had significant relationship with substance use. CONCLUSIONS: Substance use, especially methadone, has undoubtedly a significant role in both road traffic crashes and resulted injuries. The high rate of injuries on drivers influenced by methadone in traffic crashes needs to be screened and prevented. It is recommended to not only authoritatively deal with the excessive supply of methadone in the community but also restricting the driving of people receiving methadone treatment.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Detecção do Abuso de Substâncias/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Cannabis/efeitos adversos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Arch Pharm (Weinheim) ; 353(12): e2000066, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32852850

RESUMO

In this study, a number of 2,5-disubstituted 1,3,4-thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital-induced sleep test. Compounds 7 (ED50 = 1.14 and 2.72 µmol/kg in the MES and sleep tests, respectively) and 11 (ED50 = 0.65 and 2.70 µmol/kg in the MES and sleep tests, respectively) were the most potent ones in the sleep test and anticonvulsant test, showing a comparable activity with diazepam as the reference drug. The results of in vivo studies, especially the antagonistic effects of flumazenil, and also the radioligand-binding assay confirmed the involvement of benzodiazepine (BZD) receptors in the anticonvulsant and hypnotic activity of compounds 7 and 11. Finally, the docking study of compound 11 in the BZD-binding site of the GABAA (gamma-aminobutyric acid) receptor confirmed the possible binding of the compound to the BZD receptors. We concluded that the novel 1,3,4-thiadiazole derivatives with appropriate substitution at positions 2 and 5 of the heterocyclic ring had a good affinity to BZD receptors and showed significant efficacy in the pharmacological tests.


Assuntos
Anticonvulsivantes/farmacologia , Hipnóticos e Sedativos/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Convulsões/prevenção & controle , Sono/efeitos dos fármacos , Tiadiazóis/farmacologia , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/metabolismo , Anticonvulsivantes/toxicidade , Sítios de Ligação , Modelos Animais de Doenças , Desenho de Fármacos , Estimulação Elétrica , Hipnóticos e Sedativos/síntese química , Hipnóticos e Sedativos/metabolismo , Hipnóticos e Sedativos/toxicidade , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Ligação Proteica , Ensaio Radioligante , Receptores de GABA-A/metabolismo , Teste de Desempenho do Rota-Rod , Convulsões/metabolismo , Convulsões/fisiopatologia , Relação Estrutura-Atividade , Tiadiazóis/síntese química , Tiadiazóis/toxicidade
6.
Sci Rep ; 10(1): 2595, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054916

RESUMO

In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Piridinas/química , Piridinas/farmacologia , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/síntese química , Humanos , Simulação de Acoplamento Molecular , Pirazóis/síntese química , Piridinas/síntese química , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/metabolismo , alfa-Glucosidases/metabolismo
7.
Addict Health ; 11(1): 11-17, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31308905

RESUMO

BACKGROUND: Opium is the most commonly-used narcotic in Iran and some Asian countries. There are many reports of lead poisoning in opium users. Lead poisoning encompasses a wide range of symptoms the incidence and severity of which depend on the concentration and duration of contact with lead. The present study compares blood levels of lead in two groups of non-addicted patients and opiate addicts admitted to the intensive care unit (ICU) of a trauma referral hospital in Kerman, Iran. METHODS: Two groups of about 30 patients were compared. The first group was the patients who were known as opium addict according to the Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) and the second group was the patients who had no history of opium abuse. Patients' data were collected through a questionnaire. After determining the blood lead concentration by atomic absorption spectrophotometry (AAS) with graphite furnace, the data were analyzed by statistical tests. FINDINGS: Blood lead levels (BLLs) in both addicted and non-addicted groups showed a significant difference (P < 0.050), but there was no meaningful relationship between blood lead concentration and other factors such as age, gender, type of opium, method of consumption, amount of use, and duration of dependence. CONCLUSION: Many of opium-addicted ICU patients in Kerman had a high BLL due to opium pollution that can be harmful for these patients.

8.
Cent Eur J Immunol ; 43(2): 155-161, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30135627

RESUMO

Common variable immunodeficiency (CVID) is one of the predominant antibody deficiency disorders, some evidence of which indicates that chromosome instability is present in these patients. An increased risk of cancer in patients with CVID has been documented. This study was undertaken to highlight radiation sensitivity in CVID patients and to clarify the genetic basis of this defect in these cases. Stimulated lymphocytes of the studied subjects were exposed to low-dose gamma-rays in the G2 phase or the G0 phase of the cell cycle and chromosomal aberrations were scored. Lymphocytes of healthy individuals, ataxia telangiectasia (AT) cases and a group of acute lymphoblastic leukemia (ALL) patients were investigated in the same way as controls. By two methods of analysis (one-way ANOVA and unpaired t-test), the CVID cases were significantly more radiosensitive than healthy controls based on the results of the G2 and the G0 assays. First-degree relatives of CVID patients were radiosensitive by the micronucleus assay which showed a significant difference as compared with normal controls (p = 0.001). In conclusion, this study may support that chromosomal radiosensitivity in CVID patients is a marker of genetic predisposition to the disease. The results might be a clue to describe the increased risk of cancer in CVID patients.

9.
Addict Health ; 9(4): 199-205, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30574282

RESUMO

BACKGROUND: Methamphetamine (MAMP) as a recreational drug has devastating effects on the central nervous system (CNS). Several studies have shown that MAMP has inhibitory effects on oogenesis and spermatogenesis, and causes impaired fertility. This study designed to investigate the effect of mAM Padministration on histological changes and spermatogenesis indices in the testis of adult male rats. METHODS: In this experimental study, 50 male Wistar rats were randomly divided into control (received no treatment, n = 10), vehicle (received saline for 7 and 14 days, n = 20), and experimental group [received MAMP, 5 ml/kg, intraperitoneal (IP) for 7 and 14 days, n = 20]. Testicular tissue samples were stained by hematoxylin and eosin (H&E) technique. For histological study, we counted the number of spermatogonia, spermatocytes and Leydig cells. Spermatogenesis indices which include: tubular differentiation index (TDI), spermiogenesis index (SI), repopulation index (RI) and the mean seminiferous tubules diameter (MSTD) were studied. Data were analyzed by one-way ANOVA, using SPSS software. P < 0.05 was considered statistically significant. FINDINGS: This study showed that MAMP caused a significant decrease in number of seminiferous tubules cells and spermatogenesis in treated group compared with the control group. Moreover, results showed a significant decrease in spermatogenesis indices including TDI, SI, RI, and MSTD in 14th day, compared to control group (P < 0.001). CONCLUSION: The data showed the adverse effects of MAMP administration (for 7 and 14 days) on testes structure and spermatogenesis indices in rat testis tissue. The underlying mechanism(s) needs further investigation.

10.
J Evid Based Complementary Altern Med ; 22(1): 37-40, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26865602

RESUMO

BACKGROUND AND AIM: Migraine is a common form of headache that affects patients quality of life negatively. In addition to pharmacologic treatment, there are a variety of nonpharmacologic treatments for migraine headache. In present study, we examined the effect of prayer on intensity of migraine pain. METHODS: In a prospective, randomized, controlled trial from October 2013 to June 2014, this study has been conducted in Kerman, Iran. We randomly assigned 92 patients in 2 groups to receive either 40 mg of propranolol twice a day for 2 month (group "A") or 40 mg of propranolol twice a day for 2 months with prayer (group "B"). At the beginning of study and 3 months after intervention, patients' pain was measured using the visual analogue scale. RESULTS: At the beginning of study and before intervention, the mean score of pain in patients in groups A and B were 5.7 ± 1.6 and 6.5 ± 1.9, respectively. According to results of independent t test, mean score of pain intensity at the beginning of study were similar between patients in 2 groups (P > .05). Three month after intervention, mean score of pain intensity decreased in patients in both groups. At this time, the mean scores of pain intensity were 5.4 ± 1.1 and 4.2 ± 2.3 in patients in groups A and B, respectively. This difference between groups was statistically significant (P < .001). CONCLUSIONS: The present study revealed that prayer can be used as a nonpharmacologic pain coping strategy in addition to pharmacologic intervention for this group of patients.


Assuntos
Cura pela Fé , Transtornos de Enxaqueca/terapia , Religião , Adulto , Feminino , Humanos , Irã (Geográfico) , Masculino , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto Jovem
11.
Drug Chem Toxicol ; 40(2): 235-240, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27461518

RESUMO

OBJECTIVE: Concern exists regarding the possible hazards to the personnel handling anti-neoplastic drugs. The purpose of the present study was to assess the genotoxicity induced by anti-neoplastic agents in oncology department personnel. MATERIALS AND METHODS: To do this, the frequency of chromosomal aberrations (CAs) induced in peripheral blood lymphocytes was assessed at G0 phase of the cell cycle using metaphase analysis, cytokinesis block-micronucleus (MN) assay and sister chromatid exchange (SCE) assay. These cytogenetic end points were measured among 71 nurses in oncology department and 10 drugstore personnel handling and preparing anti-neoplastic drugs. The results were compared to those of 74 matched nurses for age and sex not exposed to any anti-neoplastic agents. RESULTS: There was no significant difference between the age of study subjects and control group (p > 0.05). The results showed that the mean frequency of cytogenetic damages in terms of CAs [chromatid breaks (p = 0.01), chromosome breaks (p = 0.005), total CAs (p = 0.001)], MN formation (p = 0.001), and SCE (p = 0.004) in lymphocytes of personnel handling anti-neoplastic drugs were significantly higher than those in control unexposed group. CONCLUSION: Results of the present study demonstrate the cytogenetic damage in peripheral blood lymphocytes of oncology department personnel. Suitable training and proper knowledge when handling anti-neoplastic drugs are emphasized to avoid potential health hazards caused by cytostatic agents.


Assuntos
Antineoplásicos/efeitos adversos , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Linfócitos/efeitos dos fármacos , Oncologia , Recursos Humanos de Enfermagem Hospitalar , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Serviço de Farmácia Hospitalar , Troca de Cromátide Irmã/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Linfócitos/patologia , Masculino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Pessoa de Meia-Idade , Medição de Risco , Recursos Humanos , Adulto Jovem
12.
Addict Health ; 8(4): 211-217, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28819551

RESUMO

BACKGROUND: Iran is one of the major consumers of opium and opiate substances in the world. Addiction has become a very important issue in the 21st century and an urgent one in Iran. The consumption of this substance leaves a variety of impacts on the human body. The goal of this study is to investigate the changes of the biochemical parameters derived from opiate substances in addicts during their treatment. METHODS: This is a cross-sectional research that focused on 40 individuals dependent on the consumption of opium. Their blood samples were taken before and during treatment, and their fasting blood sugar (FBS), sodium, calcium, phosphorus, creatinine, urea, uric acid, total protein, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol were measured. Data were analyzed by SPSS using paired t-test. FINDINGS: The results showed that serum uric acid, LDL, cholesterol, and the total protein levels significantly decreased during the treatment in comparison with the time before the treatment (P < 0.050). Yet, the serum fasting glucose, urea, creatinine, HDL, triglycerides, calcium, phosphorous, sodium, and potassium showed no significant change the time prior and during the treatment. CONCLUSION: Given the findings of the analysis, opium addiction has a number of destructive impacts on the lipid profile and uric acid. In addition, the level of total protein decreased during the treatment.

13.
Addict Health ; 7(1-2): 54-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26322211

RESUMO

BACKGROUND: Many of lay person believe that opium lowers blood glucose. However some studies show the opposite results. In this study, we tried to evaluate the effect of opium on blood glucose and insulin resistance. METHODS: This comparative study including 53 addicts in case groups who used opium just in the form of smoking and 55 non-addicts in a control group, took part in the study, after proving not to be opium users. After taking blood samples, their fasting blood glucose (FBG), fasting blood insulin and lipid profiles were evaluated. Furthermore, insulin resistance index was analyzed via the homeostatic model assessment of insulin resistance (HOMA-IR) formula with the cut-off points of 7.2 and 7.1. FINDINGS: Age and gender were not significantly different between the groups. There was no significant difference regarding the prevalence of insulin resistance between the two groups, according to the cut-off points of 7.1 and 7.2 (P = 0.196 and P = 0.248, respectively). Mean insulin resistance index was not significantly different between the two groups (P = 0.325). In the case group, fasting blood insulin was considerably lower (P = 0.025) and fasting blood sugar (FBS) was significantly higher (P = 0.016) than the control group. CONCLUSION: According to the level of insulin and FBS in addicts, it does not seem that opium has a significant effect on reducing the blood glucose and insulin resistance.

14.
J Evid Based Complementary Altern Med ; 20(3): 199-202, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25868567

RESUMO

INTRODUCTION: The use of medicinal plants has dramatically increased in recent years. Given the increasing rate of hypertension and medical plants usage by these patients and considering drug interactions due to concomitant use with drugs, the present study aims to evaluate the rate of medicinal plants usage in hypertensive patients. METHODS: This is a cross-sectional study (descriptive-analytical) in which 650 hypertensive patients referring to the subspecialty clinic of Kerman were questioned about medicinal plants usage by a medicinal plants questionnaire. Among these patients, there were 612 who consented to participate. After the variables were described, the data were finally analyzed using Stata 12. RESULTS: The average age of those using these drugs in the past year was 58.8 ± 10 years. Of the total number of participants using medicinal plants, there were 58 males (23.5%) and 122 females (33.4%). There were 129 participants (72.5%) using medicinal plants through self-administration, 17 participants (9.5%) on experienced users' advice, 16 participants (9%) as administered by herbalists, and 11 participants (6%) as administered by doctors. However, the most important resources for using a drug that prevents hypertension were family and friends (74 participants; 41.5%) and doctors (13 participants; 7.3%). According to the results, there was no significant difference between the level of education and medicinal plants usage (P = .95); however, there was a significant difference between gender and medicinal plants usage (P = .009). DISCUSSION: According to the results indicating the relatively high prevalence of medicinal plants usage and their arbitrary use by hypertensive patients without consulting a specialist, it seems necessary to plan for more effective and secure public education and train people to provide herbal drug services for various diseases with hypertension being the most common one.


Assuntos
Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Fitoterapia/estatística & dados numéricos , Preparações de Plantas/uso terapêutico , Idoso , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade
15.
Arch Pharm (Weinheim) ; 348(5): 330-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25787800

RESUMO

A novel series of N-(2-(piperazin-1-yl)phenyl)aryl carboxamide derivatives were simply synthesized by Ugi-multicomponent reaction as ß-secretase (BACE1) inhibitors. The BACE1 inhibitory activity of the synthesized compounds was examined using a Forester resonance energy transfer (FRET)-based assay. Among the tested compounds, the N-(5-bromo-2-(4-phenylpiperazine-1-yl)phenyl)thiophene-carboxamide derivative 14 containing the N-cyclohexyl indole acetamide moiety showed superior BACE1 inhibition at 10 and 40 µM. The results of the molecular docking study indicated that compound 14 establishes favorable hydrogen bonding interactions with the catalytic amino acid residues Asp228 and Thr72 and could be well accommodated in the flap region and P2 and P'2 pockets of the BACE1 active site.


Assuntos
Amidas/farmacologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Piperazinas/farmacologia , Inibidores de Proteases/farmacologia , Amidas/síntese química , Amidas/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/química , Ácido Aspártico Endopeptidases/metabolismo , Sítios de Ligação , Domínio Catalítico , Desenho Assistido por Computador , Desenho de Fármacos , Transferência Ressonante de Energia de Fluorescência , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Piperazinas/síntese química , Piperazinas/metabolismo , Inibidores de Proteases/síntese química , Inibidores de Proteases/metabolismo , Conformação Proteica , Relação Estrutura-Atividade
16.
Mol Divers ; 19(2): 273-81, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25613858

RESUMO

A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 µM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 µM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.


Assuntos
Aminas/síntese química , Aminas/toxicidade , Aminas/química , Linhagem Celular , Humanos , Concentração Inibidora 50
17.
J Diabetes Metab Disord ; 13(1): 5, 2014 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-24393239

RESUMO

BACKGROUND: A number of abnormalities has been identified among drug addicted users especially heroin addicts. However, there are a few studies to assess the opium effects on thyroid hormones. the aim of the present study is to investigate the effect of opium on the thyroid function tests. METHOD: In this case-control, 50 male addicts, aged 20-50 years, with history of addiction to opium lasting more than two years, and 50 male non-addicts as control group were randomly selected. 10 cc blood sample was taken for measurements of TSH, total T4 and T3, free T4 and T3, and T3 resin uptake (T3RU) and 50 cc urine sample for opium testing. RESULTS: The univariate analysis revealed that there was not a significant association between opium and serum levels of T4 and TSH, but compared with control group, a slight increase in total T3 and a decrease in T3RU were observed among addicts (P < 0.05). In multivariate analysis, opium was also found to exert a lowering effect on serum free T4 level after adjusting of age and cigarette smoking (P < 0.05). CONCLUSION: The findings of the present study demonstrated that opium can influence on thyroid function by increasing total T3 and decreasing T3RU and free T4 levels.

18.
Addict Health ; 6(3-4): 138-45, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25984281

RESUMO

BACKGROUND: The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. METHODS: In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. FINDINGS: According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. CONCLUSION: According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients.

19.
Iran J Basic Med Sci ; 17(9): 694-701, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25691947

RESUMO

OBJECTIVES: Smoking opium/cigarette is a global health concern. The aim of this study was to examine learning and memory of rat male offsprings whose mothers had been exposed to either opium or morphine with nicotine during pregnancy. MATERIALS AND METHODS: Wistar rats were used for the experiments. In the female rats, opium, morphine and nicotine dependencies were induced by daily injections of drug solution for 10 days before mating. Spatial memory was tested by Morris water maze test in male pups at the postnatal day 60. The duration that took until the rats found the platform in the maze and also their swimming speed were recorded. RESULTS: An increase in the platform finding duration was observed for the pups of dependent mothers in comparison with the control in the training trial (P<0.05). Prenatal exposure to opium/morphine and nicotine significantly decreased the time spent in the trigger zone to find the hidden platform (P<0.05) but had no significant effect on the swimming speed in the probe test. However, no significant difference was observed in the learning and memory behavior of offspring whose mothers received morphine, opium, nicotine or the co-administration of either morphine or opium with nicotine. CONCLUSION: The present study showed that the opium, morphine and nicotine abuse and co-administration of opium/morphine with nicotine during pregnancy may cause deficits in spatial learning of male rat offspring. Based on our data, no synergistic effects of co-drug administration were observed on learning and memory in male rat offspring.

20.
Am J Addict ; 23(1): 48-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24313241

RESUMO

BACKGROUND: Long-term consumption of opioid compounds, even after withdrawal, affects serum biochemical parameters. Investigating these alterations is a new approach in substance abuse studies. METHOD: This study investigated clinical laboratory results in men who are currently active, recently abstinent and non-heroin users. Participants (N = 240) of this matched cohort study included heroin dependent men referred for abstinence treatment, volunteer men who did not abuse opioids matched for age, sex, body mass index, and educational level (control group). The groups were further sub-divided for analysis into (a) continuous heroin users for more than 2 years (N = 70), the dependent group; (b) heroin abusers with 1 month abstinence period (N = 70), identified as ex-heroin dependents; and (c) a matched, non-dependent control group (N = 100). All participants were tested for fasting blood sugar (FBS), sodium, potassium, calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin. RESULTS: Compared to the control group, ex-heroin dependents showed decreased FBS and significantly higher sodium, creatinine, and cholesterol levels. Compared to the heroin dependent group, the ex-heroin dependents showed significant differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No significant differences were noted between ex-heroin dependents and controls in potassium, calcium, UA, BUN, TGs, total protein, and thrombin time. CONCLUSION: These results demonstrate altered laboratory markers in long-term heroin dependents as well as ex-heroin dependents and suggest the need for further identification, population distribution, and etiological understanding of these biomarkers in individuals who have abused heroin.


Assuntos
Biomarcadores/sangue , Dependência de Heroína/sangue , Síndrome de Abstinência a Substâncias/sangue , Adulto , Glicemia , Proteínas Sanguíneas , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Estudos de Casos e Controles , Colesterol/sangue , Creatinina/sangue , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Proteínas , Protrombina/análise , Sódio/sangue , Triglicerídeos/sangue , Ácido Úrico/sangue
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