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      • KCI등재

        Recent progress in drying technologies for improving the stability and delivery efficiency of biopharmaceuticals

        Emami Fakhrossadat,Keihan Shokooh Mahsa,Mostafavi Yazdi Seyed Jamaleddin 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.1

        Background Most biopharmaceuticals are developed in liquid dosage forms that are less stable than solid forms. To ensure the stability of biopharmaceuticals, it is critical to use an effective drying technique in the presence of an appropriate stabilizing excipient. Various drying techniques are available for this purpose, such as freeze drying or lyophilization, spray drying, spray freeze-drying, supercritical fluid drying, particle replication in nonwetting templates, and fluidized bed drying. Area covered In this review, we discuss drying technologies and their applications in the production of stable solid-state biopharmaceuticals, providing examples of commercially available products or clinical trial formulations. Alongside this, we also review how different analytical methods may be utilized in the evaluation of aerosol performance and powder characteristics of dried protein powders. Finally, we assess the protein integrity in terms of conformational and physicochemical stability and biological activity. Expert opinion With the aim of treating either infectious respiratory diseases or systemic disorders, inhaled biopharmaceuticals reduce both therapeutic dose and cost of therapy. Drying methods in the presence of optimized protein/stabilizer combinations, produce solid dosage forms of proteins with greater stability. A suitable drying method was chosen, and the process parameters were optimized based on the route of protein administration. With the ongoing trend of addressing deficiencies in biopharmaceutical production, developing new methods to replace conventional drying methods, and investigating novel excipients for more efficient stabilizing effects, these products have the potential to dominate the pharmaceutical industry in the future.

      • Oxaliplatin, 5-Fluorouracil and Leucovorin (FOLFOX-4) as First Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer

        Haghighi, Shirin,Kasbkar, Hadi,Esmaeilpour, Keihan,Yasaei, Mehrdad Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

        Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

      • Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

        Bidgoli, Sepideh Arbabi,Khorasani, Hoda,Keihan, Heideh,Sadeghipour, Alireza,Mehdizadeh, Abolfazl Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

        Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

      • KCI등재

        Reoperation etiologies in the initial hospital stay after liver transplantation: a single-center study from Iran

        Seyed Mohammad Reza Nejatollahi,Maryam Nazari,Keihan Mostafavi,Fariba Ghorbani 대한이식학회 2023 Korean Journal of Transplantation Vol.37 No.2

        Background: Liver transplantation (LT) is widely recognized as a life-saving therapy for patients with end-stage liver disease. However, due to certain posttransplant complications, reoperations or endovascular interventions may be necessary to improve patient outcomes. This study was conducted to examine reasons for reoperation during the initial hospital stay following LT and to identify its predictive factors. Methods: We evaluated the incidence and etiology of reoperation in 133 patients who underwent LT from brain-dead donors over a 9-year period based on our experiences. Results: A total of 52 reoperations were performed for 29 patients, with 17 patients requiring one reoperation, seven requiring two, three requiring three, one requiring four, and one requiring eight. Four patients underwent liver retransplantation. The most common cause of reoperation was intra-abdominal bleeding. Hypofibrinogenemia was identified as the sole predisposing factor for bleeding. Frequencies of comorbidities such as diabetes mellitus and hypertension did not differ significantly between groups. Among patients who underwent reoperation due to bleeding, the mean plasma fibrinogen level was 180.33±68.21 mg/dL, while among reoperated patients without bleeding, it was 240.62±105.14 mg/dL (P=0.045; standard mean difference, 0.61; 95% confidence interval, 0.19–1.03). The initial hospital stay was significantly longer for the reoperated group (47.5±15.5 days) than for the non-reoperated group (22.5±5.5 days). Conclusions: Meticulous pretransplant assessment and postoperative care are essential for the early identification of predisposing factors and posttransplant complications. In order to enhance graft and patient outcomes, any complications should be addressed without hesitation, and appropriate intervention or surgery should not be delayed.

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