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عضویت

جستجوی مقالات مرتبط با کلیدواژه « rifampin » در نشریات گروه « پزشکی »

  • Shahrzad Shokoofi, Ayda Esmaeili *, Ali Yekanlou

    Coagulopathy as a reversible dose-dependent side effect of rifampin is rarely observed in patient on rifampin in associate to inducing vitamin K deficiency. We reported a middle-aged man on a brucellosis three-drug regimen (including rifampin) who was admitted to the hospital due to a rheumatoid arthritis flare-up with increased partial thrombin time and international normalized ratio. Abnormal coagulation tests were discovered as an unintentional finding in the absence of clinical signs of bleeding. However, the coagulation tests returned to normal in 48 hours by withdrawing rifampin and administering 2.5 mg of oral vitamin K. The patient was discharged with a new brucellosis regimen including doxycycline and trimethoprim/sulfamethoxazole.

    Keywords: Rifampin, Coagulopathy, Vitamin K, Adverse Drug Reaction, Case Report}
  • رضا حسین دوست، نگار معتکف کاظمی، بهاره خضرایی*، علیرضا تاجیک، منوچهر بشیری نژاد، سمانه احمدی، مینوش شعبانی برزگر
    سابقه و هدف

    سودوموناس آئروژینوزا مقاوم به چند دارو، به آنتی بیوتیک های مختلفی مقاومت دارد و یکی از مشکل زا ترین عفونت های بیمارستانی است که با عوارض و مرگ و میر همراه است. کورکومین یا دی فرولوئیل متان یک آنتی اکسیدان قوی است که در زردچوبه وجود دارد و خواص آنتی بیوتیکی آن توجه پژوهشگران را به خود جلب کرده است. این ماده می تواند در مولکول های دیگر نفوذ کند؛ از این رو مورد توجه پژوهشگران در زمینه های درمانی و پزشکی قرار گرفته است. این پژوهش قصد دارد تا اثر سینژیک کورکومین را با سه آنتی بیوتیک ریفامپین، مروپنم و کورکومین علیه باکتری سودوموناس آیروژینوزا بررسی کند.

    روش کار

    در این مطالعه  تجربی، کورکومین در غلظت های 20، 40، 80  و 100 میکروگرم بر میلی لیتر عصاره گیری شد. از آنتی بیوتیک های ریفامپین، مروپنم و آمیکاسین نیز در همین غلظت ها عصاره گیری به عمل آمد و اثر آنها بر میانگین و انحراف معیار هاله رشد باکتری سودوموناس آیروژینوزا بررسی شد. درنهایت ترکیبی از آنتی بیوتیک ها و کورکومین در نسبت های 75:25، 50:50 و 25:75 ساخته شد و اثر آن بر میانگین و انحراف معیار قطر هاله عدم رشد باکتری سودوموناس آیروژینوزا بررسی شد. در این مطالعه برای تعیین پارامتریک یا ناپارامتریک بودن داده ها از آزمون کولموگروف- اسمیرنوف استفاد شد و در ادامه با توجه به نتیجه حاصل شده از آزمون کولموگروف- اسمیرنوف، از آزمون مقایسه میانگین استفاده شد.

    یافته ها

    با افزایش نسبت کورکومین و آنتی بیوتیک ها، میانگین و انحراف معیار  قطر هاله عدم رشد علیه میکروب سودوموناس آیروژینوزا نسبت به آنتی بیوتیک به تنهایی افزایش داشته (ریفامپین- کورکومین 0/033P-value =، مروپنم- کورکومین 0/006P-value =، آمیکاسین- کورکومین 0/003P-value =) و با افزایش میزان آنتی بیوتیک و رسیدن این نسبت به مقدار 25:75 (به ترتیب کورکومین: آنتی بیوتیک) میانگین و انحراف معیار قطر هاله عدم رشد علیه میکروب سودوموناس آیروژینوزا با شدت بیشتری افزایش پیدا کرد. هاله رشد آنتی بیوتیک های ریفامپین، مروپنم، آمیکاسین به تنهایی به ترتیب برابر 0/0 ± 8/88،  0/1 ± 31/11، 0/0 ± 32/29بود و در ترکیب با کورکومین به ترتیب برابر 2/8 ± 24/5، 0/7 ± 47/6، 4/1 ± 49/8بود. (تمام P-value ها کمتر از 0/05).

    نتیجه گیری

    کورکومین دارای اثر سینژیک بر فعالیت آنتی بیوتیک های ریفامپین، مروپنم و آمیکاسین است و با افزایش نسبت کورکومین، میزان اثرگذاری آن بیشتر می شود.

    کلید واژگان: کورکومین, آمیکاسین, ریفامپین, مروپنم, سودوموناس آیروژینوزا}
    Reza Hoseinidoust, Negar Motakef, Bahare Khazrai*, Alireza Tajik, Manuchehr Bashirynejad, Samaneh Ahmadi, Minoosh Shabani Barzegar
    Background and Aim

    Resistance to various antibiotics is one of the most problematic hospital complications and a mortality cause. Curcumin or diferuloylmethane is a strong antioxidant present in turmeric, and its antibiotic properties have attracted the attention of researchers. Also, this substance can penetrate other molecules. This research aims to investigate the synergistic effect of curcumin with three antibiotics rifampin, meropenem, and curcumin against Pseudomonas aeruginosa.

    Methods

    In this experimental study, curcumin was extracted at concentrations of 20, 40, 80, and 100 µg/ml. Antibiotics rifampin, meropenem, and amikacin were extracted at the same concentrations and their effect on the mean and standard deviation of the growth halo of Pseudomonas aeruginosa bacteria was investigated. Finally, a combination of antibiotics and curcumin in ratios of 75:25, 50:50 and 25:75 was made its effect on the mean and standard deviation of the halo diameter of non-growth of Pseudomonas aeruginosa bacteria was investigated. In this study, the Kolmogorov-Smirnov test was used to determine whether the data were parametric or non-parametric, and then, according to the results of the Kolmogorov-Smirnov test, the mean comparison test was used.

    Results

    By increasing the ratio of curcumin and antibiotics, the mean and standard deviation of the diameter of the non-growth halo against Pseudomonas aeruginosa increased compared to the antibiotic alone (rifampin- curcumin       P-value = 0/033, meropenem- curcumin P-value = 0/006, amikacin- curcumin P-value = 0/003). Also, with the increase of the amount of antibiotic and this ratio reached 25:75 (respectively curcumin: antibiotic), the mean and standard deviation of the diameter of the non-growth halo against Pseudomonas aeruginosa increased more strongly. The        non- growth halo of antibiotics rifampin, meropenem, and amikacin alone were 8/88 ± 0.0 mm, 31/11 ± 0/1 mm,       32/29 ± 0/0 mm, respectively, and in combination with curcumin were 24/5 ± 2/8 mm, 47/6 ± 0/7 mm, 49/8 ± 1/4 mm, respectively (all P-values less than 0/05).

    Conclusion

    Curcumin has a synergistic effect on the activity of rifampin, meropenem and amikacin antibiotics, and with increasing curcumin ratio, its effectiveness increases.

    Keywords: Cercomin, Amikacin, Rifampin, Mropenem, Pseudomonas aeruginosa}
  • Leila Heidari, Gholamreza Rafiei Dehbidi, Ali Farhadi, Golnar Sami Kashkooli, FarzanehZarghampoor, Sepide Namdari, Noorossadat Seyyedi, Saeid Amirzadh Fard, Abbas Behzad-Behbahani*
    Background and Objectives

    In clinical diagnostics, molecular methods are used to detect Mycobacterium tuberculosis bacilli (MTB) and to distinguish them from non-tuberculous mycobacteria (NTM). They are also used to make the right treatment decision for the patient as soon as possible. The aim of this study was to establish a rapid and novel multiplex PCR (mPCR) assay for the detection and differentiation of MTB and NTM in a single tube.

    Materials and Methods

    100 sputum samples positive for acid-fast bacilli (AFB) were included in this study. Mycobacterial culture, biochemical tests, and antibiotic susceptibility testing were performed on samples. After alkaline decontamination, total DNA was extracted from the samples. A primer pair targeting the rpoB gene, encoding the beta-subunit of RNA poly- merase, was used to detect MTB and NTM, amplifying a 235-bp fragment of MTB and a 136-bp sequence of NTM. A pair of primers targeting a 190-bp fragment of the IS6110 region of MTB was also used to confirm the results. The sensitivity and specificity of the mPCR assay were evaluated using DNA extracted from standard strains. The amplified products were then analyzed by conventional agarose gel electrophoresis.

    Results

    Of 100 AFB smear-positive sputum samples, 92 MTB DNA, 7 NTM DNA, and one mixed-infection sample were identified in a single tube using mPCR assay. There was no correlation between the AFB degree of smear positivity and PCR results. Of seven NTM isolates, 6 (86%) were resistant to rifampin, isoniazid, and ethambutol, the three first-line anti-tuber- culosis drugs.

    Conclusion

    A single-tube mPCR assay based on the rpoB gene provides a rapid and reliable means of detecting and differ- entiating MTB and NTM in sputum specimens.

    Keywords: Isoniazid, Multiplex polymerase chain reaction, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Rifampin, Sputum}
  • مبینا نوری، لیلا فزونی*، آنیا آهنی آذری
    زمینه و هدف

    فاضلاب یکی از خطرناک ترین و مهم ترین منابع انتشار باکتری های بیماری زاست و تصفیه و تیمار آن ها همواره مویدحذف باکتری های بیماری زا نیست. انتروکوک ها به عنوان باکتری های بیماری زای فرصت طلب، سخت رشد و عامل عفونت های بیمارستانی، پراکندگی محیطی وسیعی دارند که یکی از مسیرهای انتقال آن ها به انسان، آب و فاضلاب می باشد. افزایش میزان مقاومت آنتی بیوتیکی در بین باکتری ها نشان دهنده نیاز به بررسی عوامل ضدباکتریایی جدید یا اثرات ترکیبی آن هاست. این مطالعه با هدف بررسی اثر ترکیبی لینزولید و ریفامپین در حذف انتروکوک های مقاوم به چند آنتیبیوتیک در دو پایگاه تصفیه فاضلاب استان گلستان انجام شد.

    روش بررسی

    گونه های انتروکوک از 80 نمونه ی حاصل از پایگاه های تصفیه فاضلاب در دو شهر استان گلستان (شمال ایران) شامل گرگان و بندرترکمن طی بهمن 1399 تا تیر1400 جدا شدند. جدایه ها بر اساس روش های تعداد احتمالی باکتری ها، فیلتراسیون، تست های میکروبیولوژیک و نهایتا با استفاده از ردیابی ژن اختصاصی توسط پرایمر ddlE با روش واکنش زنجیره ای پلیمراز شناسایی شدند. الگوی مقاومت آنتی بیوتیکی با روش کربی بایر و طبق دستورالعمل 2020-CLSI نسبت به شش کلاس آنتی بیوتیکی انجام شد. تعیین حداقل غلظت لینزولید در حالت منفرد و در ترکیب با ریفامپین با روش میکرودایلوشن براث انجام شد.   

    یافته ها:

     پس از بررسی فنوتیپی و تشخیص مولکولی (PCR) نمونه های فاضلاب خام و تیمارشده، در40% نمونه های فاضلاب (32 نمونه) گونه های انتروکوک شناسایی گردیدند. تتراسایکلین کم اثرترین آنتی بیوتیک گزارش شد؛ به طوری که حدود 100 درصد جدایه های انتروکوکوس فکالیس و انتروکوکوس فاسیوم به آن مقاومت نشان دادند. فراوانی انتروکوکوس فکالیس مقاوم به لینزولید 11% تایید شد. در مجموع، 20 جدایه انتروکوکی (62/5%) دارای مقاومت چندگانه بودند. حداقل غلظت مهاری لینزولید و ریفامپین که رشد 90% جدایه ها را مهار کرد (MIC90) 1 میکروگرم بر میلی لیتر و 4 برابر کمتر از فرم منفرد لینزولید (4 میکروگرم بر میلیلیتر= MIC90) بود. ضمن این که هیچ یک از جدایه های انتروکوکی به ترکیب لینزولید/ ریفامپین مقاومتی نشان ندادند (0/001=P). 

    نتیجه گیری

    نتایج حاصل از این تحقیق، حضور انتروکوکسی های مقاوم به ونکومایسین و سایر آنتی بیوتیک ها را در تصفیه خانه فاضلاب تایید نمود. اثر مطلوب ترکیب لینزولید و ریفامپین در مهار کامل جدایه های انتروکی مقاوم به چند دارو، دلالت بر هم افزایی آن ها داشت.

    کلید واژگان: انتروکوک, فاضلاب, مقاومت دارویی, لینزولید, ریفامپین}
    Mobina Noori, Leila Fozouni*, Ania Ahani Azari
    Background and Aim

    Wastewater is one of the most dangerous and important sources of pathogens and their treatment does not always guarantee the elimination of pathogenic bacteria. Enterococci, as opportunistic pathogenic bacteria, fastidious and cause of nosocomial infections, have a wide environmental distribution and one of the routes of their transmission to humans is water and wastewater. The increasing rate of drug- resistance among bacteria indicates the need for investigation of novel antibacterial agents or their combination effects. The aim of this study was to investigate the effect of linezolid in combination with rifampin on the elimination of multidrug- resistant enterococci in two treatment plants in Golestan province. 

    Materials and Methods

    Enterococcus species from eighty samples were isolated from treatment plants in two cities of the Golestan Province (North of Iran) including Gorgan and Bandar-e Torkaman during January-June 2021. The isolates were identified based on the most probable number (MPN), filtration, microbiological tests and finally by using specific gene detection by ddlE primer with polymerase chain reaction. Kirby Bauer performed an antibiotic resistance pattern according to CLSI- 2020 guidelines for six classes of antibiotics. The minimum inhibitory concentration of linezolid was determined individually and by synergist effect with rifampin by broth microdilution method. 

    Results

    After phenotypic and molecular diagnosis (PCR) of raw and treated wastewater samples, in 32 (40%) wastewater samples, enterococci species were identified and confirmed. Tetracycline was the least effective so, about 100% of Enterococcus faecalis and Enterococcus faecium isolates were resistant to it. The prevalence of linezolid-resistant E. faecalis was 11%. A total of 20 enterococcal isolates (62.5%) had multiple resistance. The concentration of linezolid in combination with rifampin, which inhibited 90% growth of the isolates (MIC90) was 1μg /ml, four-fold lower than linezolid alone (MIC90=4 μg/ml). In addition, none of the enterococci isolates showed resistance to the linezolid/rifampin combination (P=0.001).

    Conclusion

    The results of this research confirmed the presence of enterococci resistant to vancomycin and other antibiotics in the wastewater treatment plant samples in Golestan province. The favorable combination effect of linezolid and rifampin on the inhibition of multi-drug resistant isolates implies their synergy.

    Keywords: Enterococci, Wastewater, Drug Resistance, Linezolid, Rifampin}
  • جواد قاسمیان یادگاری، حمیدرضا محمدی*، گلسا حیدری، احمد آدینه، کورش قنادی، علی غفاریان بهرمان، مهرنوش محمدیان، امیرمحمد دستجردی، زهرا صارمی
    مقدمه

    ریفامپین، یکی از داروهای رایج جهت درمان بیماری سل مورد استفاده قرار می گیرد و یک عامل توکسیک قوی برای کبد به شمار می رود. هدف از این مطالعه بررسی اثرات تجویز عصاره دارچین در سمیت کبدی ناشی از داروی ریفامپین در موش صحرایی می باشد.

    مواد و روش ها

    در این مطالعه تجربی 60 رت نر از نژاد ویستار در 6 گروه  به صورت تصادفی قرار گرفت. آسیب کبدی و القا استرس اکسیداتیو با تجویز  mg/kg/day80 ریفامپین ایجاد شد. دوزهای مختلف عصاره  دارچین (50 ، 100  و 200 میلی گرم بر کیلوگرم) در سه گروه آزمایشی به صورت ‏گاواژ روزانه به موش های بیمار تجویز شد. آسیب کبدی ناشی از ریفامپین با بررسی فاکتور های بیوشیمیایی سرمی و همچنین میزان گونه های فعال اکسیژن، گلوتاتیون، ظرفیت آنتی اکسیدانی، پراکسیداسیون لیپیدی و تغییرات هیستوپاتولوژیک در بافت کبد مورد ارزیابی قرارگرفت. تحلیل داده ها با استفاده از نرم افزار Prism نسخه 6 و آزمون تحلیل واریانس یک طرفه و آزمون تعقیبی توکی انجام شد.

    یافته ها

    تجویز داروی ریفامپین به میزان mg/kg 80 برای مدت 21 روز متوالی باعث ایجاد آسیب کبدی گردید (05/0> P). از سوی دیگر تجویز دوزهای مختلف عصاره دارچین، توانست به طور معنی داری آسیب های کبدی ‏ناشی از مصرف ریفامپین را بهبود بخشید (05/0> P).

    بحث و نتیجه گیری

    طبق نتایج این مطالعه، عصاره دارچین با خواص آنتی اکسیدانی، کبد را در برابر آسیب اکسیداتیو ناشی از ریفامپین محافظت می کند. که این اثرات بهبود دهندگی، به صورت کاهش مارکرهای آسیب کبدی در سرم، ‏کاهش مارکرهای استرس اکسیداتیو و بهبود آسیب بافتی کبد نمایان گردید.

    کلید واژگان: عصاره دارچین, سمیت کبدی, ریفامپین, استرس اکسیداتیو}
    Javad Ghasemian Yadegari, Hamidreza Mohammadi*, Golsa Haidari, Ahmad Adineh, Koroush Ghanadi, Mehrnoosh Mohammadian, AmirMohammad Dastjerdi, Zahra Saremi
    Introduction

    Rifampin is one of the common drugs used to treat tuberculosis and is considered a strong toxic agent for the liver. The aim of this study is to investigate the effects of cinnamon extract administration on rifampin-induced hepatotoxicity in rats.

    Materials and methods

    In this experimental study, 60 male Wistar rats were randomly divided into 6 groups. Liver damage and induction of oxidative stress were caused by administration of 80 mg/kg/day rifampin. Different doses of cinnamon extract (50, 100 and 200 mg/kg) were administered to sick mice by daily gavage in three experimental groups. Liver damage caused by rifampin was evaluated by examining serum biochemical factors as well as the amount of reactive oxygen species, glutathione, antioxidant capacity, lipid peroxidation and histopathological changes in liver tissue. Data analysis was done using Prism version 6 software and one-way analysis of variance and Tukey's post hoc test.

    Results

    The administration of rifampin at the rate of 80 mg/kg for 21 consecutive days caused liver damage (P<0.05). On the other hand, administration of different doses of cinnamon extract could significantly improve the liver damage caused by rifampin consumption (P<0.05)

    Discussion and conclusion

    According to the results of this study, cinnamon extract with antioxidant properties protects the liver against oxidative damage caused by rifampin. These healing effects were shown in the form of reduction of liver damage markers in serum, reduction of oxidative stress markers and improvement of liver tissue damage.

    Keywords: Cinnamon extract, Hepatotoxicity, Rifampin, Oxidative stress}
  • شیما سادات فرزانه، فاطمه نوروزی، حسین فاضلی، شراره مقیم، بهرام نصر اصفهانی*

    مقدمه :

    سل (Tuberculosis) TB، همچنان به عنوان یک مشکل جدی بهداشت عمومی در سراسر جهان است و سالانه میلیون ها مرگ و میر ایجاد می کند. تخمین زده می شود که یک سوم جمعیت جهان به سل نهفته آلوده باشند. سل مقاوم در برابر دارو یک تهدید بزرگ و در حال رشد جهانی تلقی می شود. هدف از این مطالعه، تعیین حساسیت دارویی جدایه های مایکوباکتریوم توبرکولوزیس از بیماران مراجعه کننده به آزمایشگاه رفرانس سل منطقه ای استان اصفهان (ملاهادی سبزواری) نسبت به داروهای خط اول ضد سل بود.

    روش ها

    در این مطالعه، تعداد 438 جدایه ی مایکوباکتریوم توبرکلوزیس با استفاده از تست های بیوشیمیایی و تاییدیه به واسطه ی تست مولکولی از بیماران مبتلا به سل ریوی مراجعه کننده به آزمایشگاه رفرانس منطقه ای سل استان اصفهان در طول سال های 1396-98 جدا گردید، تعداد 33 ایزوله ی مقاوم به دارو بررسی شد. تست حساسیت دارویی نسبت به داروهای خط اول درمان به روش پروپورشن انجام گرفت و از سویه ی استاندارد H37Rv مایکوباکتریوم توبرکلوزیس که حساس به تمامی داروها می باشد، به عنوان کنترل استفاده شد.

    یافته ها

    از تعداد 438 جدایه، 20 جدایه (37/7 درصد) حساس و 33 جدایه (62/3 درصد) مقاوم به خط اول درمان به روش فنوتیپی بودند که به ترتیب ایزونیازید 22 جدایه (66/7 درصد)، ریفامپیسین 18 جدایه (54/5 درصد)، اتامبوتول 4 جدایه (12/1 درصد) و پیرازین آمید 5 جدایه (15/2 درصد) بود، همچنین 10 جدایه (30/3 درصد) سل مقاوم به چند دارو بودند.

    نتیجه گیری

    الگوی مقاومت دارویی در سل در هر منطقه ی جغرافیایی متفاوت است و در منطقه ی اصفهان به دلیل مقاومت رو به افزایش سل، تحقیقات بیشتری برای تعیین مقاومت مایکوباکتریوم توبرکلوزیس نیاز است.

    کلید واژگان: مایکوباکتریوم توبرکلوزیس, مقاومت دارویی, ایزونیازید, ریفامپین, اتامبوتول و پیرازین آمید}
    Shima Sadat Farzaneh, Fatemeh Norouzi, Hossein Fazeli, Sharareh Moghim, Bahram Nasr Esfahani *
    Background

    Tuberculosis (TB) remains a serious public health problem worldwide, causing millions of deaths annually. It is estimated that one-third of the world population is infected with latent TB. Drug-resistant TB is considered a major and growing global threat. In this study, we aimed to indicate the drug-susceptibility of Mycobacterium tuberculosis isolates from patients, presented to Mollahadi Sabzevari Tuberculosis Center in Isfahan, Iran to the first-line drugs.

    Methods

    In this study, Mycobacterium tuberculosis was isolated from 438 patients with pulmonary tuberculosis referred to the Regional Reference Laboratory of tuberculosis in Isfahan province during 2017-2019, 33 resistant isolates were studied. Drug susceptibility testing to first-line drugs was performed by proportion method, and the H37Rv reference strain sensitive to all drugs was used for quality control.

    Findings

    Out of 438 isolates, 20 isolates (37.7%) were drug-sensitive and 33 isolates (62.3%) were resistant to the first-line drug by phenotypic method, which was isoniazid (INH) 22 isolates (66.7%), rifampin (RIF) 18 isolates (54.5%), ethambutol (EMB) 4 isolates (12.1%) and pyrazinamide (PZA) 5 isolates (15.2%) respectively. Also, 10 isolates (30.3%) were multidrug-resistant tuberculosis (MDR-TB).

    Conclusion

    The pattern of drug resistance in Mycobacterium tuberculosis is different in each region and in the Isfahan region due to the increasing drug resistance of tuberculosis. Further research is needed to determine the drug resistance of Mycobacterium tuberculosis.

    Keywords: Mycobacterium tuberculosis, Drug resistance, Isoniazid, Rifampin, Ethambutol, Pyrazinamide}
  • Elahehnaz Parhizkar, Delaram Sadeghinia, Hamed Hamishehkar, Shadi Yaqoubi, Ali Nokhodchi, Shohreh Alipour*
    Purpose

    Pulmonary Tuberculosis (TB) is a worldwide life-threatening infection. The recommended anti-TB regimen contains oral administration of classical first-line drugs such as rifampin for 6-24 months which often leads to low patient compliance due to high adverse effects; therefore, lung localized pulmonary delivery of anti-TB agents may be a suitable alternative. Proliposomes free-flowing powders are well-known carriers for lung delivery since they can form liposomes by hydration. Liposomes are safe and useful carriers for lung delivery due to their phospholipid structure.

    Methods

    Porous lactose and mannitol as proliposome carriers were prepared by spray drying technique using sucrose and citric acid as templating agents. Design expert® software was used to develop forty formulations based on the porous and non-porous carriers, which were characterized with respect to their weight yield, density, and flowability. Rifampin-loaded hydrated liposomes were produced and evaluated for size, morphology, loading capacity and encapsulation efficiency. The optimized proliposomes in vitro release and aerosolization properties were evaluated. Solid-state analysis was confirmed by Differential Scanning Calorimetry (DSC).

    Results

    Porous lactose surface area was 80 folds higher than non-porous one, respectively. Optimized porous-based proliposome indicated the acceptable aerosolization properties, including mass median aerodynamic diameter (MMAD) of 6.21±0.36 µm and fine particle fraction (FPF) of 9.17±0.18% with a fast rifampin release (80%) within one hour. DSC results proved that there was no change in the solid-state of rifampin during the production process.

    Conclusion

    Hence, it seems; rifampin loaded inhalable proliposomes may be a suitable system for delivering liposomal rifampin into the lungs.

    Keywords: aerosolization properties, carrier porosity, dry powder, proliposome, rifampin}
  • Fahimeh Azadi, Masoomeh Rezanezhadi, Hanieh Bagheri, Laith B Alhusseini, Hamid Reza Joshaghani*
    Background and objectives

    Tuberculosis (TB) is a serious public health problem and a significant diagnostic and therapeutic challenge worldwide. Molecular diagnostic techniques are crucial parts of the World Health Organization’s new tuberculosis control strategy. This study aims to identify Mycobacterium tuberculosis and rifampin resistance in pulmonary and extra-pulmonary clinical specimens using the Gene Xpert MTB/RIF assay.

    Methods

    The study was carried out on 220 specimens from pulmonary and extra-pulmonary TB patients that were sent to the Kavosh Laboratory in Gorgan (Iran) during 2018-20. The Gene Xpert MTB / RIF method was applied to detect M. tuberculosis and rifampin resistance.

    Results

    Of 220 specimens, 15 (6.81%) were found to be positive, four (26.6%) of which were related to pulmonary and 11(73.3%) to extra-pulmonary specimens. None of the positive samples was resitant to rifampin according to assay.

    Conclusion

    Our findings demonstrate that the Gene Xpert MTB/RIF is able to accurately detect M. tuberculosis in pulmonary and extra-pulmonary specimens. The accurate and early diagnosis of TB infection allows timely therapeutic intervention, which is beneficial not only for the patient but also for possible contacts.

    Keywords: Mycobacterium tuberculosis, Tuberculosis Multidrug-Resistant, Rifampin}
  • Marianne Marianne *, Urip Harahap, Poppy Anjelisa Zaitun Hasibuan, Chintya Monica Thampati, Herman Syukur Harefa
    Introduction

    Isoniazid (INH) and rifampin (RIF) are antituberculosis drugs that can induce injury in the liver. The purpose of this study was to investigate the antioxidant and hepatoprotective activities of the ethanol extract of Curcuma heyneana rhizome on liver injury in animal model induced by INH and RIF.

    Methods

    Antioxidant activity was measured by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. All animals were divided into 7 groups. Liver injury was induced by using combination of INH at the dose of 50 mg/kg and RIF at the dose of 100 mg/kg. These drugs were administrated for 15 days along with extracts at doses of 5, 25, 125 or 625 mg/kg. Positive control group was given catechin. On the 16th day, the rats were sacrificed, blood and livers were collected for assessment of biochemical parameters like alanine transaminase (ALT) and aspartate transaminase (AST) and histological studies, respectively.

    Results

    The ethanol extract strongly scavenged DPPH with inhibition concentration 50 (IC50) of 82.48 ppm. Administration of ethanol extract of C. heyneana rhizome at the dose of 25, 125 or 625 mg/kg significantly inhibited the elevation of AST and ALT (P<0.01). Moreover, the effects caused by administration of the extracts were similar to the effects caused by catechins. Various doses of the extract could effectively reduce tissue damage.

    Conclusion

    This result suggests that ethanol extract of C. heyneana rhizome at the doses of 25, 125 and 625 mg/kg might be effective as hepatoprotective agent.

    Keywords: Curcuma heyneana, Hepatoprotective, Rifampin, Isoniazid, Antioxidant}
  • Farzaneh Bazrgari, Bahman Khameneh, Bibi Sedigheh Fazly Bazzaz, Asma Mahmoudi, Bizhan Malaekeh Nikouei *
    Objective(s)

    Staphylococcus epidermidis is a common cause of medical device-associated infections due to biofilm formation, and its elimination is extremely challenging. Although rifampin efficacy against S. epidermidis biofilms has been confirmed, its use as a single agent may lead to resistance. As such, it is assumed that the combination of rifampin and N-acetylcysteine (NAC) could exert additive effects as a mucolytic agent. The present study aimed to use a liposomal system for the delivery of these compounds to bacterial biofilm.

    Materials and Methods

    Liposomal formulations were prepared using the dehydration-rehydration method and characterized in terms of the size, zeta potential, and encapsulation efficacy. In addition, the ability of various formulations in the eradication of bacterial biofilm and inhibition of biofilm formation was assessed based on the optical density ratio.

    Results

    The zeta potential of the liposomes was positive, and the mean size of these liposomal formulations was less than 200 nanometers. Liposomal rifampin was the most effective formulation against S. epidermidis, and the anti-biofilm activity of most of the formulations was concentration-dependent and time-dependent.

    Conclusion

    According to the results, the rifampin-loaded liposomes were effective against S. epidermidis biofilm formation.

    Keywords: Biofilm, Nanoliposomes, N-acetyl cysteine, Rifampin}
  • Molecular Detection of Isoniazid and Rifampin Resistance in Mycobacterium tuberculosis Isolates from Lorestan Province, Iran from 2014 to 2017
    Fariborz Heidary, Hamed Esmaeil Lashgarian, Maryam Karkhane, Shahin Najar Peerayeh *
    Background

    A rise in multidrug-resistant tuberculosis (MDR-TB), which is defined as the resistance to the two most effective first-line therapeutic drugs, Isoniazid (INH) and Rifampin (RIF), threatens global public health worldwide. Resistance of Mycobacterium tuberculosis to INH results from mutations in several genes most commonly in katG gene, and resistance to RIF is due to mutations in rpoB gene. Therefore, rapid diagnosis of MDR-TB is of high importance in controlling the disease progress and outcome. The accurate detection of the resistant TB strains can be accelerated by developing molecular tests.

    Objectives

    The aim of the present local study was to isolate MDR-TB from the patients who were the residents in the west of Iran and examination the frequency of MDR-TB between patients of Lorestan province for the first time and assess the mutations in the regions related to RIF/INH resistance via PCR and sequencing methods.

    Methods

    In this study, 106 isolates of M. tuberculosis were selected in health centers of Lorestan, Iran from 2014 to 2017. After culturing M. tuberculosis isolates on Löwenstein-Jensen medium, classical susceptibility testing proportional method against INH and RIF was performed. After DNA extraction, PCR and sequencing were used to detect mutations related to RIF and INH resistance.

    Results

    The results demonstrated 3.8%, 0.9%, and 0.9% frequency for INH + RIF, INH and RIF resistance, respectively. Importantly, 4 out of 6 isolates harbored mutations in codon290 of katG gene. Also, these isolates contained mutations in codon339 of rpoB gene. No mutation was observed in inhA gene of M. tuberculosis isolates.

    Conclusions

    The results suggest that molecular techniques can be used as a rapid method for the identification of drug resistance in clinical isolates of M. tuberculosis. DNA sequencing has a high sensitivity for the detection of resistance mutations to RIF and INH in MDR-TB cases. Also, the results showed that the most frequent resistance associated-mutations occurred in codon290 of katG and codon 339 rpoB gene segments.

    Keywords: Multidrug Resistance, Mycobacterium tuberculosis, Isoniazid, Rifampin}
  • معصومه صوفیان، سعید فولادوند، فرشیده دیدگر، علیرضا ژاپونی نژاد، علیرضا آموزنده نوباوه، احسان الله غزنوی راد*
    زمینه و هدف

    درمان عفونت های ناشی از آسینتوباکتر بائومانی به علت مقاومت های دارویی چندگانه مشکل است. هدف این مطالعه تعیین اثربخشی درمان ترکیبی کلیستین و ریفامپیسین در درمان پنومونی وابسته به ونتیلاتور به علت آسینتوباکتر بائومانی مقاوم به ایمی پنم می باشد.

    روش بررسی

    در یک مطالعه تحلیلی از آبان 1393 تا خرداد 1394 تعداد 50 بیمار در مرکز آموزشی درمانی ولیعصر (عج) اراک تحت درمان استاندارد با کلیستین و ریفامپین قرار گرفتند و متغیرهای بالینی آنالیز گردیدند. 

    یافته ها: 

    31 بیمار (62%) بیمار پس از درمان ترکیبی بهبود یافتند، چهار بیمار (8%) در اثر عفونت و 15 بیمار (30%) به دلایل دیگر فوت کردند. میانگین میزان نیتروژن اوره خون و کراتینین به طرز معناداری افزایش داشت و تب، فشارخون، شمارش گلبول های سفید، شمارش افتراقی و مورتالیتی کاهش پیدا کردند.

    نتیجه گیری:

     کلیستین و ریفامپین یک ترکیب ایمن و موثر در درمان پنومونی وابسته به ونتیلاتور ناشی از ایزوله های آسینتوباکتر بائومانی مقاوم به ایمی پنم است.

    کلید واژگان: آسینتوباکتر بائومانی, درمان ترکیبی, کلیستین, ریفامپین}
    Masoomeh Sofian, Saeed Fooladvand, Farshideh Didgar, Alireza Japoni Nejad, Alireza Amouzandeh Nobaveh, Ehsanollah Ghaznavi Rad*
    Background

    It is difficult to treat infections caused by Acinetobacter baumannii due to multiple drug resistance. The aim of this study was to determine the efficacy of combination therapy with two broad-spectrum antibiotics colistin and rifampin on clinical and para clinical indexes of the patients with ventilator-dependent pneumonia due to imipenem-resistant to A. baumannii in intensive care units of a tertiary hospital.

    Methods

    In a descriptive cross-sectional study, fifty patients admitted to the intensive care units in Vali-Asr Hospital, Arak, Iran, from October 2014 to May 2015, with established ventilator-associated pneumonia were subjected to this study and were treated with standard dosage of colistin and rifampin daily. Once the minimum inhibitory concentration (MIC) of the A. baumannii isolates were susceptible to colistin (MIC˂2 µg/ml) and rifampin (MIC˂2 µg/ml) they were treated with three million international units of colistin in 100 ml of normal saline three times a day and 600 mg of rifampin daily. Side effects of combination therapy and variables of patients like fever, blood pressure, white blood cell count, differential count and, mortality were documented and statistically analyzed.

    Results

    31(62%) patients were improved after combined treatment with colistin and rifampin, 4(8%) patients were died due to bloodstream infection with A. baumannii and 15(30%) passed away in effect of other reasons. The mean of BUN (P=0.07) and creatinine significantly increased (P=0.02). Clinical variables such as fever, white blood cell count, white blood cell percentage and red blood cell sedimentation rate significantly decreased (P≤0.05).

    Conclusion

    Colistin and rifampicin appear to be an effective and safe combination therapy for treatment of ventilator-dependent pneumonia due to imipenem-resistant to A. baumannii

    Keywords: Acinetobacter baumannii, combination therapy, colistin, rifampin}
  • Behnam Dasht Bozorg, Ali Goodarzi, Fanak Fahimi, Payam Tabarsi, Nahid Shahsavari, Farzad Kobarfard, Farzaneh Dastan *

    Therapeutic Drug Monitoring (TDM) of first-line anti-tuberculosis (TB) drugs is a decisive tool, allowing the clinician to successfully treat TB patients. The objective of the study was to develop and optimize a simple, sensitive, and reliable high-performance liquid chromatography (HPLC) method for the simultaneous determination of isoniazid (INH), pyrazinamide (PZA), and rifampin (RIF) levels in human plasma. Nicotinamide was used as the internal standard and the samples were prepared after protein precipitation using acetonitrile and zinc sulfate. The separation was achieved using a C18 reversed-phase applying gradient elution. The mobile phase was a combination of water–methanol solution with a ratio of 95:05 (v/v) at the initial phase. All calibration curves had good linearity (r2 > 0.99) and the inter- and intra-day RSDs were lower than 15%. The limit of detection with a signal-to-noise ratio (S/N) of 3:1 was 0.16, 0.5, and 0.33 μg mL–1 for INH, PZA, and RIF, respectively. The method presented here was selective, sensitive, and reproducible, and could be used for therapeutic drug monitoring in the patients who were under treatment with these drugs.

    Keywords: Anti-TB drugs, Therapeutic Drug Monitoring, HPLC-UV, Isoniazid, Pyrazinamide, Rifampin}
  • Mehmet Selim, Selim Demir, Elif Acar, Müge Koşucu, Süleyman Caner, Erhan Arslan *
    Background
    Ischemic brain damage can be explained by the emergence of acute focal or global neurological findings caused by vascular occlusions or hemorrhages. Even in non-fatal cases, stroke is an important pathologic condition with a severe impact on the quality of life, and patients require considerable assistance in the daily lives.
    Objectives
    The purpose of this study was to investigate the effect of rifampicin on malondialdehyde (MDA) levels and neurological examination of the hippocampal region in rats with transient cerebral ischemia.
    Methods
    This experimental study has been performed in a university-affiliated animal lab, Trabzon, Turkey, in 2016. Thirty-eight Sprague Dawley rats weighing 220 - 280 g were used. In this two-vessel occlusion and hypotension ischemia-reperfusion model, the bilateral carotid arteries were temporarily clipped (30 minutes), and blood was withdrawn up to 3 mL of intracardiac volume before the induction of hypotension. After 30 minutes, the clips were removed, and a reperfusion medium was created. One group of 12 rats received intraperitoneal injections of 30 mg/kg of rifampicin every day, and after a 30-minute bilateral carotid artery clipping and hypotension (10 mL/kg). Another group of 12 rats underwent a 30-minute bilateral carotid artery clipping and hypotension (10 mL/kg). The third group consisting of 7 rats underwent skin laceration only. The final group of 7 rats received anesthesia for only 15 minutes. Neurological examinations were performed at the end of days 1, 4, 7, and 10 in all groups. At the end of the 10th day, the animals were euthanized, and their brain tissues were removed. The hippocampi were removed from the brains for biochemical analysis and stored at -76°C in a deep freeze. Ischemic changes in the brain were assessed biochemically by measuring MDA levels in both blood and brain tissue.
    Results
    There was no statistically significant difference between the groups in terms of the mean tissue MDA levels (P = 0.112), but a significant difference was determined in the mean serum MDA values (P = 0.033). Serum MDA values significantly differed between the Group 1 and Group 2 (P = 0.030), but not between Group 1 and Group 3 (P = 0.58). Serum MDA values were also significantly different between Group 2 and Group 3 (P = 0.019), and between Group 2 and Group 4 (P = 0.035).
    Conclusions
    Rifampicin could exhibit a neuroprotective effect on cerebral ischemia-reperfusion injury.
    Keywords: Brain Ischemia, Carotid Arteries, Hippocampus, Ischemia, Reperfusion Injury, Ischemic Attack, Malondialdehyde, Neuroprotective Agents, Rats, Rifampin, Transient}
  • سید مجتبی سهروردی، فرهاد صراف زاده، علی خسروی، عبدالرضا حسن زاده*
    مقدمه
    سل یکی از اصلی ترین عوامل مرگ و میر در بیماری های عفونی است. با توجه به اهمیت رعایت رژیم دارویی، جهت کنترل و پیشگیری از مقاومت دارویی، تصمیم گرفته شد، میزان رعایت رژیم دارویی توسط بیماران مسلول شهر کرمان بررسی شود.
    روش بررسی
    این مطالعه به صورت مقطعی و سرشماری انجام گرفت که نهایتا 80 بیمار مطالعه را کامل نمودند. اطلاعاتی دموگرافی از طریق پرسش نامه ی خاص بیماران، جمع آوری گردید. پس از گرفتن نمونه ادراری، چند قطره ادرار به معرف خاص ایزونیازید، ریفامپین و پیرازینامید اضافه می شد و تغییر رنگ اختصاصی ایجاد شده، معرف مصرف یکی از این داروها بود. اطلاعات گردآوری شده به کمک نرم افزار SPSS Inc., Chicago, IL; Version 18 مورد تجزیه و تحلیل قرار گرفت. از آزمون کای اسکور برای بررسی ارتباط بین متغیرها استفاده گردید.
    نتایج
    نتایج این مطالعه نشان داد که در مجموع میزان همکاری بیماران در مصرف ایزونیازید 70 درصد، ریفامپین 70 درصد و پیرازینامید 1/68 درصد بوده است. کیفیت پیروی از دستورات دارویی با سن، اطلاع از عوارض ناخواسته دارویی، اعتیاد به تریاک و مدت مصرف دارو ارتباط معنی دار داشت (05/0P<) ولی با عوامل جنسیت، مدت بیماری، مصرف داروی دیگر، و حضور فرد مسلول دیگر در خانواده، ارتباط معنی داری مشاهده نگردید.
    نتیجه گیری
    این مطالعه مشخص کرد که عواملی هم چون سن، اعتیاد به تریاک، مدت درمان وآگاهی از عوارض ناخواسته داروها از جمله عوامل تاثیر گذار بر همکاری بیماران در مصرف مناسب داروها بوده است، به طوری که افراد بالای 35 سال، معتاد به تریاک، با دوره درمان طولانی و با عدم آگاهی از عوارض ناخواسته داروها به میزان کمتری مبادرت به رعایت رژیم دارویی خود نموده بودند.
    کلید واژگان: سل, همکاری در مصرف, ایزونیازید, ریفامپین, پیرازینامید}
    Seyyed Mojtaba Sohrevardi, Farhad Sarrafzadeh, Ali Khosravi, Abdolreza Hassanzadeh*
    Introdution
    Among infectious diseases, tuberculosis is one of the leading causes of death killing in nearly 1.5 million people yearly. Considering the importance of patient co-operation in drug therapy and resistance we decided to evaluate the rate of co-operation of tuberculosis infected patients in regard to their use of anti-tuberculosis drugs in Kerman.
    Methods
    This descriptive study was conducted as a sectional and census study and 80 patients succeeded to finalize it. Demographic information was collected through a questionnaire by patients. To carry out the designed test, a urinary sample was taken from each patient and a few drops of each were added to the drug-specific reagents. On the basis of color variation which is special for rifampin, isoniazid and pyrazinamide, we made a decision on the co-operation of the patients. The collected data were analyzed by the the use of SPSS software version 18 and p-value<0.05 was acceptable. To find out the relation between variables, the Chi-square test was applied.
    Results
    The results of this study showed that the total co-operation rate for patients administered with isoniazid was 70%, rifampin 70%, and pirazinamide 68.1%. The quality of adherence to drug orders with age, knowledge of unwanted adverse effects, opium addiction and duration of drug use had a significant relationship (P <0.05); but  with gender, duration of illness, use of another drug, and the presence of another TB infected in the family, no significant difference was observed.
    Conclusion
    We resulted that factors such as age, addiction and lifestyle, duration of treatment and awareness of side effects influence on the co-operation of the patients on drug usage. So that people over 35 years, addict ones, treated for a long time and in the patients with lack of awareness of drug side effects, their adherence to the treatment regimen was lower.
    Keywords: Tuberculosis, Drug adherence, Isoniazid, Rifampin, Pyrazinamide}
  • Marzieh Kazerani *, Maryam Kazerani, Kiarash Ashrafzadeh, Shamim Rahiman, Mahdi Mottaghy, Amin Samihi
    Background
    Tuberculosis (TB) is a major global health problem. The goal is to end the global TB epidemic. TB treatment averted 49 million deaths globally from 2000 to 2015. If everyone with TB had a timely diagnosis and high-quality treatment, the TB case fatality rate would be lower in all countries. The main source of infection is untreated smear positive pulmonary TB; the next step should be the examination of the sputum for Mycobacterium sp. Bacteriologic evaluation through culture and /smear microscopy is essential to monitor the response to treatment. Monitoring acid-fast bacilli (AFB) smear should be undertaken at 2, 5, and 6 months. The currently recommended treatment for the new cases of drug-susceptible TB is a 6-month regimen of 4 first-line drugs: isoniazid (INH), rifampin (RIF), ethambutol (ETM), and pyrazinamide (PZA). Treatment success rates of at least 85% for new cases of drug-susceptible TB are regularly reported to the world health organization (WHO) by its 194 member states. The global TB drug facility supplies a complete 6-month course for about US$ 40 per person.
    Objectives
    The current study aimed at evaluating the effectiveness of directly observed treatment short course (DOTS), AFB-negative/AFB-positive sputum after a 2- month treatment with the 4 first-line drugs.
    Methods
    A total of 700 patients with tuberculosis referred to Sanabad Health Center of Mashhad, Iran from March 2005 to March 2008 were retrospectively studied. Then, 360 new smear-positive pulmonary TB were chosen. After 2 months of treatment with 4 anti-tubercular agents, age, gender, nationality, and AFB -negative, AFB-positive of sputum smear were recorded in 2 groups.
    Results
    Females were infected more than males. There were treatment success rates of at least %86.4 for new cases of drug-susceptible TB. Age, gender, and nationality were not related to the changes in sputum (negative-positive).
    Conclusions
    DOTS were effective in the current study. In low- and middle-income countries, in patients with TB cavity, diabetes, malnutrition, immune disorder, and cigarettes smoking, the sputum smear and culture testing on the days 15 and 30 of treatment until the completion of the treatment should be done.
    Keywords: Tuberculosis, Pulmonary Tuberculosis, Anti-tubercular Agents, Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Mycobacterium tuberculosis}
  • Mahdi Behdani, Hoshang Rafatpanah, Alireza Mohammadzadeh*, Kiarash Ghazvini, Mostafa Amiri, Jalal Mardaneh
    Background
    Resistance to rifampin in multidrug-resistant M. tuberculosis (MDR-TB) is one of the major threats to the global public health system.
    Objectives
    The aim of the present study was to explore the molecular characterization of resistance against rifampin amongst multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates obtained from patients.
    Methods
    In this study, we used XDR (n = 6), MDR (n = 9) and rifampin sensitive (n = 39) isolates whose drug susceptibility patterns were identified by proportion method. A simple single-step multiplex-allele specific-polymerase chain reaction (MAS-PCR) assay was optimized to detect the three most frequent mutations in rifampin resistance-determining region (RRDR) fragment of rpoB gene. Additionally, single-strand conformational polymorphism (SSCP)-PCR and Sequencing were utilized.
    Results
    Out of nine MDR isolates, five were detected by MAS-PCR as rifampin resistant (sensitivity; 55.5%). In comparison with the proportion method, the sensitivity of SSCP for XDR, MDR and rifampin sensitive isolates were 83.3%, 77.7% and 97.4%, respectively. The DNA sequencing revealed that three of the 6 XDR isolates had several silent mutations, one isolate had one silent mutation, one strain had no mutations and only one isolate had mutations at codon 531.
    Conclusions
    In sum, although the molecular methods are rapid, they are not able to identify resistance against rifampin efficiently.
    Keywords: Mycobacterium tuberculosis, Multidrug, Resistant, Extensively Drug, Resistant, Rifampin}
  • Jalil Rashedi, Behroz Mahdavi Poor, Abdolnasser Rafi, Mohammad Asgharzadeh, Jalal Abdolalizadeh, Seyyed Reza Moaddab
    Background
    Republic of Azerbaijan is considered as an area with high prevalence of multi-drug resistant tuberculosis. Uncontrolled travelling of Azerbaijanis people to Iran is the issue that needs to be considered as an important issue.
    Methods
    This study was conducted on 32 patients with tuberculosis from Baku–Nakhchivan and 48 patients from Iran during 2012 to 2014. Colonies of Mycobacterium tuberculosis were examined after isolating them from patients using proportional method on Lowenstein-Jensen media regarding resistance encounter with Rifampin, Isoniazid and Ethambutol.
    Results
    Among M. tuberculosis isolates belonging to 32 foreign patients; 69%, 72% and 56% of them were resistant to Rifampin, Isoniazid and Ethambutol, respectively (multidrug resistance tuberculosis: MDR-TB: 62.5%). From 48 isolates of Iranian patients; 8%, 4% and 4% were resistant to Rifampin, Isoniazid and Ethambutol, respectively (MDR-TB: 2.1%).
    Conclusions
    Resistant strains are common in Baku-Nakhchivan’s people. To prevent the transmission of these strains to Iranians, strategies such as; establishing a medical campus in border lines of both countries for clinical examinations and conducting screening tests regarding tuberculosis infection in applicants for entering Iran must be taken in to account.
    Keywords: Drug resistance, Iran, Proportional, Rifampin, tuberculosis}
  • Meysam Mohseni, Kambiz Gilani, Zohreh Bahrami, Noushin Bolourchian, Seyed Alireza Mortazavi
    The goal of this research is preparation, optimization and in-vitro evaluation of rifampin-loaded silica nanaoparticles in order to use in pulmonary drug delivery. Nanoparticles are exhaled because of thier small size, Preparation of nanoaggregates in micron-sized scale and re-disrpersion of them after the deposition in the lung is one approach in order to overcome this problem, which we used in this research. Rifampin was selected as a model lipophilic molecule since it is a well-documented and much used anti tuberculosis drug. A half factorial design was used to identify the significant parameters of spray drying process. The results showed that feed concentration, feed pH and interaction between feed flow rate and gas atomizer flow rate had statistically significant effect on the particle size of nanoaggregates. For optimization of spray drying process, the Box-Behnken design was employed and finally a quadratic equation which explains the relation between independent variables with aerodynamic diameter of nanoaggregates was obtained. Rifampin-loaded silica nanoaggregates underwent different in-vitro tests including: SEM, Aerosol performance and drug release. The in vitro drug release was investigated with buffer phosphate (pH=7.4). Regarding the drug release study a triphasic pattern of release was observed. The rifampin-loaded silica nanoaggregates was capable of releasing 90% drug content after 24h in combination patterns of release. The prepared rifampin-loaded nanoaggregates seem to have potential for use in a pulmonary drug delivery.
    Keywords: Spray drying, Rifampin, experimental design, silica nanoaggregates, Drug release}
  • مهرداد نشاط قراملکی*، داریوش مهاجری
    زمینه و هدف
    داروی ضد سل ریفامپین، برای کبد سمی است. این مطالعه با هدف تعیین اثرات پیشگیرانه عصاره سیاه دانه (Nigella sativa Linn) از سمیت کبدی ریفامپین در موش صحرایی انجام شد.
    روش بررسی
    در این مطالعه تجربی آزمایشگاهی، 40 سر موش صحرایی نر ویستار به طور تصادفی به چهار گروه مساوی تقسیم شدند: 1- گروه شاهد؛ 2- گروه داروی سمی؛ 3- گروه شاهد مثبت و 4- گروه تحت درمان با عصاره که به ترتیب نرمال سالین، ریفامپین (با دوز 500 میلی گرم بر کیلوگرم)، سیلیمارین (با دوز 50 میلی گرم بر کیلوگرم) توام با ریفامپین و عصاره الکلی سیاهدانه (دوز 250 میلی گرم بر کیلوگرم) به علاوه ریفامپین را از طریق گاواژ به مدت یک ماه دریافت کردند،. در پایان، سطح سرمی آلانین آمینو ترانسفراز، آسپارتات آمینو ترانسفراز، آلکالین فسفاتاز، بیلی روبین، آلبومین و پروتئین موش ها اندازه گیری شد. میزان مالون دی آلدئید و فعالیت سوپراکسید دیسموتاز، کاتالاز، گلوتاتیون پراکسیداز و گلوتاتیون ردوکتاز کبد اندازه گیری شد. آسیب شناسی بافتی جهت ارزیابی درجات مختلف آسیب کبد انجام گرفت. گروه ها با آزمون آماری آنالیز واریانس یک طرفه و آزمون تعقیبی توکی مقایسه شدند.
    یافته ها
    سیلیمارین و عصاره سیاهدانه به طور معنی داری میزان سرمی آنزیم های شاخص عملکرد کبد، بیلی روبین و میزان مالون دی آلدئید کبد را کاهش و سطوح آلبومین، پروتئین سرم و سطوح کبدی آنزیم های آنتی اکسیدانی را در موش های تیمارشده با ریفامپین افزایش داد (0/01>p). در آسیب شناسی بافتی، سیلیمارین و عصاره سیاهدانه، آسیب ناشی از ریفامپین را بهبود بخشید. نتایج هیستوپاتولوژی با یافته های بیوشیمیایی هم راستا بود.
    نتیجه گیری
    طبق نتایج این مطالعه، عصاره سیاهدانه با خواص آنتی اکسیدانی، کبد را در برابر آسیب اکسیداتیو ناشی از ریفامپین محافظت می کند.
    کلید واژگان: سیاهدانه, ریفامپین, کبد, آنتی اکسیدان ها, موش صحرایی}
    Mehrdad Neshat Gharamaleki*, Daryoush Mohajeri
    Background And Objectives
    Anti-tuberculosis drug, rifampin, is toxic for liver. This study was conducted to determine the preventive effects of black cumin (Nigella sativa Linn.) extract against rifampin-induced hepatotoxicity in rats.
    Methods
    In this experimental study, 40 male Wistar rats were randomly divided into 4 equal groups: 1- control group, 2- toxic drug group, 3- positive control group, and 4- extract treatment group, respectively received normal saline, rifampin (at a dose of 500mg/kg), silymarin (at a sose of 50mg/kg) plus rifampin, and ethanolic extract of black cumin (250mg/kg) plus rifampin, daily through gavage for one month. Finally, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, albumin, and protein, were assessed. Malondialdehyde level and activities of liver superoxide dismutase, catalase, glutathione peroxidise, and glutathione reductase, were measured. Histopathological analysis was performed to evaluate the various degrees of liver injury. The groups were compaired using statistical tests of one-way ANOVA and Tukey, s post-test.
    Results
    Silymarin and black cumin extract significantly decreased the serum levels of liver function biomarkers, bilirubin, and malondialdehyde and increased the serum levels of albumin and protein and the levels of liver antioxidant enzymes in the rats treated with rifampin (p<0.01). Histopathologically, silymarin and black cumin extract improved the rifampin-induced hepatic injury. Histopathological results were consistent with biochemical findings.
    Conclusion
    Accordind to the results of this study, black cumin extract with antioxidant properties, protects liver tissue against rifampin-induced oxidative damage.
    Keywords: Nigella sativa, Rifampin, Liver, Antioxidants, Oxidative Stress, Rats}
نکته
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