The Effects of PLGA Microparticles on Intestinal Absorption of P-glycoprotein Substrate Using the Everted Rat Intestinal Sac Model

Katayoun Derakhshandeh,Aidin Hosseinalizadeh,Maryam Nikmohammadi 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

In addition to the effects of physical processes (solubility, tissue permeability, and formulation factors), p-glycoprotein (P-gp) efflux across the apical membrane of enterocytes can affect the rate and amount of compound diffusing across the basolateral membrane of the intestine and entering the blood stream. The first objective was the evaluation of a possible role of intestinal P-gp in the kinetic absorption of a model drug: furosemide. To achieve this goal, two series of transport experiments, apical to basolateral (A → B) and basolateral to apical (B → A) with and without verapamil -a known P-gp inhibitor- were performed. The second objective was to evaluate whether encapsulation into polymeric microparticles might improve the oral absorption of a poorly permeable drug. Thus, spherical poly lactic-glycolic acid (PLGA) microparticles of furosemide were designed, and the concentration of transported drug was evaluated using an in situ everted rat gut sac model. The results indicated that verapamil at various drug concentrations (5-100 μg/mL) significantly decreased the B → A (2-3 fold) and increased the A → B (1.5-2 fold) permeability of furosemide, which showed that this drug could be a P-gp substrate. We found that encapsulation of furosemide in PLGA microparticles can markedly increase (2-4 fold) intestinal absorption of drug even higher than verapamil does. We conclude that biodegradable microparticles are a promising strategy to increase the bioavailability of drugs and have advantages compared to P-gp inhibitors with pharmacological and severe side effects at doses required for efflux pump inhibition.

Reversal of multidrug resistance in cancer cells by novel asymmetrical 1,4-dihydropyridines

Omidreza Firuzi,Katayoun Javidnia,Elham Mansourabadi,Luciano Saso,Ahmad Reza Mehdipour,Ramin Miri 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.11

Multidrug resistance (MDR) is an importantobstacle that limits the efficacy of chemotherapy in manytypes of cancer. In this study, 14 novel asymmetrical DHPspossessing pyridyl alkyl carboxylate substitutions at C3 andalkyl carboxylate groups at C5 in addition to a nitroimidazoleor nitrophenyl moiety at C4 position were synthesized. Calciumchannel blocking (CCB) activity was measured inguinea pig ileal longitudinal smooth muscle. Cytotoxicitywas tested on 4 human cancer cell lines, while MDR reversalcapacity was examined on P-glycoprotein overexpressingdoxorubicin resistant MES-SA-DX5 and compared withnon-resistant MES-SA cells. Compounds showed differentCCB (IC50: 29.3 nM–4.75 lM) and cytotoxic activities(IC50: 6.4 to more than 100 lM). Several compounds havingnitrophenyl moiety at C4, could significantly reverse resistanceto doxorubicin at 0.5 and 1 lM. The most active oneswere 7e and 7g containing ethyl carboxylate and isopropylcarboxylate at C5, respectively. CCB activity, which isconsidered an undesirable effect for these agents, of 7e and7g were 33 and 20 times lower than nifedipine, respectively. In conclusion, the newly synthesized asymmetrical DHPcompounds showed promising MDR reversal and antitumoralactivities with low CCB effects and could be of therapeuticvalue in drug resistant cancer.

Comparison of Vitex agnus-castus Extracts with Placebo in Reducing Menopausal Symptoms: A Randomized Double-Blind Study

Rozita Naseri,Vahid Farnia,Katayoun Yazdchi,Mostafa Alikhani,Behrad Basanj,Safora Salemi 대한가정의학회 2019 Korean Journal of Family Medicine Vol.40 No.6

Background: Menopausal symptoms have remarkable negative effects on women’s quality of life, justifying the need to assess various therapeutic options. This research aimed to determine the effectiveness of Vitex agnus-castus extracts in alleviating menopausal symptoms in comparison with that of placebo. Methods: This study was a randomized controlled double-blind clinical trial with a study group of 52 women referred to a clinic in Kermanshah in 2017. The participants were randomly divided into two groups: Vitex group (26 subjects) and placebo group (26 subjects). Menopausal symptoms were assessed using the Greene Scale before and 8 weeks after the intervention. Results: After the intervention, the mean scores for total menopausal disorder, anxiety, and vasomotor dysfunction were significantly lower in the Vitex group than in the placebo group (P<0.05). The mean scores of the variables of somatic complications, depression, and sexual dysfunction did not show significant differences between the Vitex and placebo groups (P>0.05). Conclusion: Administration of Vitex agnus-castus extracts as a phytoestrogenic medicine can alleviate menopausal symptoms in women.

Leech Therapy for Linear Incisional Skin-Wound Healing in Rats

Kaveh Darabi Darestani,Sayid Mahdi Mirghazanfari,Katayoun Gohari Moghaddam,Somayeh Hejazi 사단법인약침학회 2014 Journal of Acupuncture & Meridian Studies Vol.7 No.4

Background: The aim of this study was to investigate the effects of leech therapy (LT), in com- parison with topical phenytoin (PHT), on incisional skin-wound healing in animal models. Methods: This experimental study included 15 male rats (5 animals in 3 groups) with approxi- mately equal body weights (350 ? 10 g). Skin wounds with lengths of 20 mm and depths of 0.5 mm were made on the dorsolateral region of rats 4 cm from the spine. The first group (PHT group) was treated daily with topical PHT (1%) while the second group (LT group) received LT at the beginning of the experiment. The control group received neither the drug nor the therapy. Wound healing was evaluated every day, and the study was continued until the wound had completely healed. Changes in the areas and the appearances of the skin wounds and his- tological differences (at the end of the experiment) were used to investigate the differences in wound healing among the groups. Results: The process of wound healing was significantly faster in the group treated with LT (p < 0.05) than in the group treated with the PHT. Conclusion: The study results showed that LT improved incisional skin-wound healing in rats.

Inhibitors of Alzheimer’s BACE-1 with 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structure

Ramin Miri,Omidreza Firuzi,Nima Razzaghi-Asl,Katayoun Javidnia,Najmeh Edraki 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.4

b-site amyloid precursor protein cleavingenzyme (BACE-1) is a validated target for Alzheimer therapydue to its distinctive role in pathogenesis of AD. In thepresent contribution, a series of new 3,5-bis-N-(aryl/heteroaryl)carbamoyl-4-aryl-1,4-dihydropyridine structureswere synthesized as BACE-1 inhibitors (6a–6n). In vitroBACE-1 inhibitory activities were determined by enzymaticfluorescence resonance energy transfer assay. Synthesizeddihydropyridine (DHP) analogues exhibited weak to goodinhibitory activities while 6i, 6n and 6a were found to be themost potent molecules with 83.76, 79.45 and 72.47 %BACE-1 inhibition at 10 lM, respectively. Structure binding/activity relationship elucidations revealed that superiorBACE-1 inhibitory activities were observed for DHPderivatives bearing fused/non-fused thiazole groups andparticularly 3,5-bis-N-(6-ethoxy-2-benzothiazolyl) moiety. Binding maps showed that enhanced activity may beattributed to the additional H-bond and hydrophobic interactionswith S2–S3 subpockets of BACE-1.

Review Article : The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain

( Taraneh Moini Zanjani ),( Haleh Ameli ),( Farzaneh Labibi ),( Katayoun Sedaghat ),( Masoumeh Sabetkasaei ) 대한통증학회 2014 The Korean Journal of Pain Vol.27 No.3

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

A Comparative Study of the Effect of Flaxseed Oil and Sunflower Oil on the Coagulation Score, Selected Oxidative and Inflammatory Parameters in Metabolic Syndrome Patients

( Atefeh Akrami ),( Elham Makiabadi ),( Moein Askarpour ),( Katayoun Zamani ),( Amir Hadi ),( Amin Mokari-yamchi ),( Siavash Babajafari ),( Shiva Faghih ),( Abdollah Hojhabrimanesh ) 한국임상영양학회 2020 Clinical Nutrition Research Vol.9 No.1

Metabolic syndrome (MetS) is a chronic disease with inflammatory and hypercoagulable states. The current study aimed to compare the effects of flaxseed oil and sunflower oil consumption on the coagulation score and selected oxidative and inflammatory parameters in patients with MetS. In this randomized controlled clinical trial, 60 patients with MetS were allocated into 2 groups. One group received 25 mL/day flaxseed oil and the other group received 25 mL/day sunflower oil for 7 weeks. Maintenance diet including 15% protein, 55% carbohydrate, and 30% fat from daily total energy intake was designed for each participant. Serum levels of total antioxidant capacity (TAC) and interleukin 6 (IL-6), as well as coagulation score were measured before and after the intervention. Three 24-hour food records were taken during the study. Fifty-two of participants (27 in sunflower oil and 25 in flaxseed oil groups) completed the study. The baseline characteristics and dietary intakes were similar between patients. After 7 weeks, no significant difference was observed between the 2 groups regarding the serum TAC level and coagulation score (p > 0.05). However, serum IL-6 levels significantly decreased in the flaxseed oil group compared to the sunflower oil group (p = 0.017). No side effect was observed during the study due to the use of sunflower and flaxseed oils. We observed that consumption of flaxseed oil improved serum IL-6 levels but had no effect on oxidative stress and coagulation score in patients with MetS. Further studies are needed to confirm the veracity of our results.

The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain

Zanjani, Taraneh Moini,Ameli, Haleh,Labibi, Farzaneh,Sedaghat, Katayoun,Sabetkasaei, Masoumeh The Korean Pain Society 2014 The Korean Journal of Pain Vol.27 No.3

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

The effect of the Iranian family approach-specific course (IrFASC) on obtaining consent from deceased organ donors’ families

Ehsan Radi,Matin Ghanavati,Batoul Khoundabi,Jamal Rahmani,Katayoun Nahafizadeh,Mahdi Shadnoush,Behrooz Broumand,Omid Ghobadi 대한이식학회 2022 Korean Journal of Transplantation Vol.36 No.4

Background: A family approach and obtaining consent from the families of potential brain-dead donors is the most important step of organ procurement in countries where an opt-in policy applies to organ donation. Health care staff’s communication skills and ability to have conversations about donation under circumstances of grief and emotion play a crucial role in families’ decision-making process and, consequently, the consent rate. Methods: A new training course, called the Iranian family approach-specific course (IrFASC), was designed with the aim of improving interviewers’ skills and knowledge, sharing experiences, and increasing coordinators’ confidence. The IrFASC was administered to three groups of coordinators. The family consent rate of participants in the same intervals (12 months for group 1, 6 months for group 2, and 3 months for group 3) was measured before and after the training course. The Wilcoxon signed-rank test was used to make comparisons. Results: The family consent rate was significantly different for all participants before and after the training, increasing from 50.0% to 62.5% (P=0.037). Furthermore, sex (P=0.005), previous training (P=0.090), education (P=0.068), and duration of work as a coordinator (P=0.008) had significant effects on the difference in families’ consent rates before and after IrFASC. Conclusions: This study showed that the IrFASC training method could improve the success of coordinators in obtaining family consent.