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111.
Quique Bassat Bernhards Ogutu Abdoulaye Djimde Kirstin Stricker Kamal Hamed 《Antimicrobial agents and chemotherapy》2015,59(8):4366-4374
Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated Plasmodium falciparum malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance. 相似文献
112.
Amit Ranjan Sabiha Shaik Arif Hussain Nishant Nandanwar Torsten Semmler Savita Jadhav Lothar H. Wieler Niyaz Ahmed 《Antimicrobial agents and chemotherapy》2015,59(10):6087-6095
Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum β-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT2 gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131. 相似文献
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Erkan Cure Medine C. Cure Levent Tumkaya Yildiray Kalkan Ibrahim Aydin Aynur Kirbas Arif Yilmaz Suleyman Yuce Mehmet F. Gokce 《Saudi Journal Of Gastroenterology》2014,20(5):297-303
Background and Aim:
Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury.Materials and Methods:
Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure.Results:
The I/R group''s TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes.Conclusion:
Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery. 相似文献117.
Safar Farajnia Vahideh Ahmadzadeh Asghar Tanomand Kamal Veisi Shiva Ahdi Khosroshahi Leila Rahbarnia 《Immunopharmacology and immunotoxicology》2014,36(5):297-308
Recombinant antibodies are increasingly being employed as therapeutic agents especially in combination with anti-cancer drugs. The single-chain antibody fragments are small antigen-binding proteins which provide the most commonly used antibody formats for diagnostic and therapeutic purposes. These antibody fragments have more rapid tumor penetration and clearance from the serum relative to full-length monoclonal antibodies. There are in vitro antibody-display technologies such as phage display, cell surface display, ribosome display and mRNA display that can be used to isolate high specificity and affinity single-chain antibodies against a wide variety of targets. We review these strategies for generation of stable and active antibody fragments in the present article. 相似文献
118.
S. M. Shakil Hussain Muhammad Shahzad Kamal Theis Solling Mobeen Murtaza Lionel Talley Fogang 《RSC advances》2019,9(52):30154
The solubility and heat stability of surfactants are the prerequisites for their oilfield applications. Most commercial surfactants undergo hydrolysis at high temperature and prolonged heating at 40 °C or above leads to decomposition. In this report, three cationic poly(ethylene oxide) gemini surfactants (GSs) containing flexible and rigid spacers were synthesized for oilfield applications. The chemical structures of the GSs were elucidated with the aid of 13C NMR, 1H NMR, FT-IR, and MALDI-TOF MS. The GSs exhibit pronounced solubility in deionized water, seawater, and formation brine and no cloudiness, phase separation, or precipitation were detected after keeping GS solutions in an oven at 90 °C for three weeks. According to thermal gravimetric analysis, the degradation temperature of all the GSs was above 240 °C, which is higher than the existing oilfield temperature (≥90 °C). The critical micelle concentration (CMC) of the synthesized GSs decreases upon increasing the temperature. Additionally, CMC values were observed to increase even further with increasing salinity. The low CMC values of gemini surfactants containing a flexible structure indicate that they create a more closely packed micelle structure compared with gemini surfactants with a rigid structure. The distinct surface and thermal features of the synthesized GSs reveal them to be appropriate materials for high salinity and elevated temperature reservoirs.Synthesis of new cationic poly(ethylene oxide) gemini surfactants containing flexible and rigid spacer groups to tolerate harsh reservoir condition. 相似文献
119.
Ibrahim H. Eissa Ahmed M. Metwaly Amany Belal Ahmed B.M. Mehany Rezk R. Ayyad Khaled El‐Adl Hazem A. Mahdy Mohammed S. Taghour Kamal M.A. El‐Gamal Mohamad E. El‐Sawah Souad A. Elmetwally Mostafa. A. Elhendawy Mohamed M. Radwan Mahmoud A. ElSohly 《Archiv der Pharmazie》2019,352(11)
In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G‐2, Hep‐2, and Caco‐2). Compounds 18b, 19b, 23, 25b , and 26 showed strong potencies against all tested cell lines with IC50 values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC50 values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities. Compounds 19b and 19c exhibited high activities against Topo II (IC50 = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC50 value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell‐cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G‐2 cells. It has revealed cell‐cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl‐2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA–Topo II complex to examine the binding patterns of the synthesized compounds. 相似文献
120.