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21.
Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals
Khakzad MR Mirsadraee M Mohammadpour A Ghafarzadegan K Hadi R Saghari M Meshkat M 《Pulmonary pharmacology & therapeutics》2012,25(2):163-168
IntroductionGoblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.MethodsMale BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale.ResultsInflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57 ± 1.30% for low dose; 1.50 ± 0.93% for high dose versus 12.93 ± 7.55%, P < 0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45 ± 0.30 for low dose; 0.81 ± 1.00 for high dose versus 2.85 ± 0.86 in the sensitized control group, P < 0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1 ± 0.43 versus 4.7 ± 0.96, P < 0.05 and 91.8 ± 47.7 versus 14.8 ± 4.6, P < 0.01, respectively).ConclusionVerapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation. 相似文献
22.
Seyyed Mojtaba Mousavi Foo Wah Low Seyyed Alireza Hashemi Nurul Asma Samsudin Mohammad Shakeri Yulisa Yusoff Mansoor Rahsepar Chin Wei Lai Aziz Babapoor Sadaf Soroshnia Su Mei Goh Sieh Kiong Tiong Nowshad Amin 《RSC advances》2020,10(22):12851
Nowadays, chemotherapy is one of the crucial and common therapies in the world. So far, it has been revealed to be highly promising, yet patients suffer from the consequences of severe negative medical dosages. In order to overcome these issues, the enhancement of photothermal chemotherapy with reduced graphene oxide (rGO) as a photothermal agent (PTA) is widely utilised in current medical technologies. This is due to its high near-infrared region (NIR) response, in vitro or in vivo organism biocompatibility, low risk of side effects, and effective positive results. Moreover, rGO not only has the ability to ensure that selective cancer cells have a higher mortality rate but can also improve the growth rate of recovering tissues that are untouched by necrosis and apoptosis. These two pathways are specific diverse modalities of cell death that are distinguished by cell membrane disruption and deoxyribonucleic acid (DNA) disintegration of the membrane via phosphatidylserine exposure in the absence of cell membrane damage. Therefore, this review aimed to demonstrate the recent achievements in the modification of rGO nanoparticles as a PTA as well as present a new approach for performing photochemotherapy in the clinical setting.rGO of QD-rGO nanocomposite could absorb and convert into heat when harvested under NIR radiation, resulting cell death with reduction of fluorescence. 相似文献
23.
Preparation and evaluation of 188Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy 下载免费PDF全文
Mina Jamre Mojtaba Shamsaei Mostafa Erfani Sodeh Sadjadi Mohammad Ghannadi Maragheh 《Journal of labelled compounds & radiopharmaceuticals》2018,61(8):586-594
Radioembolization with radioactive microspheres has been an effective method for the treatment of liver lesions. The aim of this study was to prepare carrier‐free 188Re loaded poly (L‐lactic acid) (PLLA) microspheres through 188Re sulfide colloidal nanoparticles (188Re‐SC nanoparticles). The formation of 188Re‐SC nanoparticles was confirmed by ultraviolet‐visible spectrophotometry. The labeling yield of 188Re‐SC nanoparticles was verified using the RTLC method. Effects of synthesis parameters on morphology and size of prepared 188Re‐sulfide colloidal‐PLLA microspheres (188Re‐SC‐PLLA microspheres) were studied by scanning electron microscopy. In vitro stability of 188Re‐SC‐PLLA microspheres was investigated in normal saline at room temperature and in human serum at 37°C. In vivo distribution studies and gamma camera imaging were performed in healthy BALB / c mice. The microspheres could be prepared with sizes between 13 and 48 μm (modal value 29 μm) and radiolabeling efficiency >99%. After incubation, the microspheres were found stable in vitro up to 72 hours. The biodistribution after intravenous injection in healthy BALB / c mice showed high accumulation in lung as a first capture pathway organ for microsphere followed by great retention over 48 hours for these microspheres. These data show that 188Re‐SC‐PLLA microspheres are suitable candidate for clinical studies. 相似文献
24.
Ali Ramazani Mojtaba Keramati Hojat Malvandi 《Pharmaceutical development and technology》2018,23(9):911-920
AbstractPurpose: Artemisinin (ART) has anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and anti-malarial effects, but its application is limited due to its low water solubility and poor oral bioavailability. In this study, the bioavailability, water solubility, and anti-plasmodial property of ART were improved by PCL–PEG–PCL tri-block copolymers.Methods: The structure of the copolymers was characterized by 1H NMR, FT-IR, DSC, and GPC techniques. ART was encapsulated within micelles by a single-step nano-precipitation method, leading to the formation of ART-loaded PCL–PEG–PCL micelles. The obtained micelles were characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). The in vivo anti-plasmodial activity of ART-loaded micelles was measured against Plasmodium berghei infected Swiss albino mice.Results: The results showed that the zeta potential of ART-loaded micelles was about ?8.37?mV and the average size was 91.87?nm. ART was encapsulated into PCL–PEG–PCL micelles with a loading capacity of 19.33?±?0.015% and encapsulation efficacy of 87.21?±?3.32%. In vivo anti-plasmodial results against P. berghei showed that multiple injections of ART-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of ART.Conclusion: These results suggested that PCL–PEG–PCL micelles would be a potential carrier for ART for the treatment of malaria. 相似文献
25.
Purpose: One of the consequences of trauma-related injuries is disability. There are more than one billion people with disabilities worldwide. Disability in people reduces their quality of life. The goal of this study was to determine the rate of post-trauma stress and disability related to trauma in the population over 15 years old in Kashan during a solar year of 2018-2019.
Methods: This is a cross-sectional population-based study. A cluster sampling method was used in the city of Kashan, and 3880 persons were interviewed with individuals randomly selected in each household. If a person had trauma during one year ago, the World Health Organization Disability Assessment Schedule 2.0 and Post Trauma Stress Disorder (PTSD) Checklist were applied for further interview. Data were analyzed using Chi-square test or t-test.
Results: Among the 3880 participants residing in Kashan, 274 (7.1%) reported a history of traumatic injury during one year ago in 2018-2019. Incidence of all injuries was estimated to be 70.61 (62.60-78.70) per 1000 people. For the trauma population, 213 (77.7%) were male and 75.1% were married. About half of them (50.3%, 138/274) aged 21e39 years. The most common cause of injuries was related to traffic accidents: 140 (51.1%). Of the 274 trauma participants, 47 (17.2%) reported PTSD; 244 (89.1%) had a mild disability, and 30 (10.9%) reported moderate disability.
Conclusion: One of the main causes of disability in the human community is the traumatic injuries. According to the results of this study, 89.1% of trauma participants have sustained at last mild disability following trauma. These people require follow-up and post-treatment support. It should be noted that psychological complications such as PTSD are as significant as physical symptoms. 相似文献
26.
Arash Khorrami Mojtaba Hammami Mehraveh Garjani Nasrin Maleki-Dizaji Alireza Garjani 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1)
Background
The inflammatory responses play a major role in the pathogenesis of acute myocardial infarction (MI). Early inhibition of inflammation may improve post MI cardiac function. The aim of this study was to investigate the effects of tacrolimus on cardiac function, hemodynamic parameters as well as histopathologic and electrocardiographic changes in isoproterenol-induced myocardial infarction.Methods
Male Wistar rats were randomly divided into six groups of control, isoproterenol alone, tacrolimus alone, and isoproterenol plus tacrolimus (0.5, 1 and 2 mg/kg). Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days to induce myocardial infarction, and simultaneously tacrolimus was administered orally twice a day for three days.Results and conclusions
Administration of isoproterenol resulted in myocardial edema and necrosis as well as a marked reduction in the left ventricular systolic pressure (LVSP), left ventricular contractility (LVdP/dtmax) and relaxation (LVdP/dtmin) along with a severe elevation in left ventricular end-diastolic pressure (LVEDP). Isoproterenol also elevated the ST-segment and suppressed the R-amplitude and R-R interval on ECG. It was found that all doses of tacrolimus could amend the ECG pattern and ameliorated the isoproterenol induced disturbances in cardiac function. Acute and short term treatment with tacrolimus at dose of 2 mg/kg significantly (P < 0.001) improved LVdP/dtmax from 2712 ± 82 in myocardial infarcted rats to 4592 ± 149 mmHg/sec. Similarly, tacrolimus lowered LVEDP from 17.6 ± 0.68 in MI group to the value of 5.6 ± 0.22 mmHg (P < 0.001). Furthermore, tacrolimus was found to reduce malondialdehyde concentration in serum and myocardium by 50-70% (P < 0.001).The results of this study showed that acute treatment with tacrolimus, coincided with the occurrence of myocardial infarction, strongly protected the myocardium against the isoproterenol-induced myocardial infarction; where this might be due to the anti-inflammatory properties of tacrolimus. 相似文献27.
Atabak Najafi Mojtaba Mojtahedzadeh Keyvan Haji Ahmadi Mohammad Abdollahi Maryam Mousavi Legese Chelkeba Farhad Najmeddin Arezoo Ahmadi 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1):57
Background
Sepsis complication is a major cause of death in multiple trauma critically ill patients. Defensin (cysteine rich anti-microbial peptides), as an important component of immune system, might play an important role in this process. There is also rising data on immunological effects of N-acetyl-cysteine (NAC), a commonly used anti-oxidant in oxidative stress conditions and glutathione (GSH) deficiencies. The aim of the present study was to evaluate the potential beneficial effects of NAC administration on multiple trauma patients with sepsis.Methods
In a prospective, randomized controlled study, 44 multiple trauma critically ill patients who were mechanically ventilated and met the criteria of sepsis and admitted to the intensive care unit (ICU) were randomized into two groups . Control group received all standard ICU therapies and NAC group received intravenous NAC 3 gr every 6 hours for 72 hours in addition to standard therapies. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality were recorded. Levels of serum Immunoglobulin M (IgM), Human β-Defensin 2 (HβD2) and GSH were assessed at baseline and 24, 72, 120 hours after intervention.Results
During a period of 13-month screening, 44 patients underwent randomization but 5 patients had to be excluded. 21 patients in NAC group and 18 patients in control group completed the study. For both groups the length of ICU stay, SOFA score and systemic oxygenation were similar. Mortality rate (40% vs. 22% respectively, p = 0.209) and ventilator days (Mean ± SD 19.82 ± 19.55 days vs. 13.82 ± 11.89 days respectively, p = 0.266) were slightly higher for NAC group. IgM and GSH levels were similar between two groups (p = 0.325, 0.125 respectively), HβD2 levels were higher for NAC group (at day 3).Conclusion
High dose of NAC administration not only did not improve patients’ outcome, but also raised the risk of inflammation and was associated with increased serum creatinine. 相似文献28.
29.
30.
Mojtaba Oraki Kohshour Sako Mirzaie Majid Zeinali Mansour Amin Mohammad Said Hakhamaneshi Ali Jalili Nader Mosaveri Mostafa Jamalan 《Chemical biology & drug design》2014,83(3):259-265
Trastuzumab (Herceptin®) is a monoclonal antibody (mAb) for specific ablation of HER2‐overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano‐immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2‐overexpressing SK‐BR‐3 and also HER2‐negative MCF‐7 cancer cell lines were examined. Cells treated with trastuzumab‐MWCNT conjugates were irradiated with near‐infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab‐MWCNT and trastuzumab‐DT conjugates were significantly efficient in the specific killing of SK‐BR‐3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab‐DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT‐immunoconjugates. In conclusion, our data demonstrated that trastuzumab‐MWCNT is a promising nano‐immunoconjugate for killing of HER2‐overexpressing cancerous cells. 相似文献