Synthesis and Studies of Novel Optically Active Schiff's Base Derivatives and their Antimicrobial Activities

Abstract: Several new Schiff's base derivatives were prepared by condensing various substituted benzaldehyde with 1-(4-aminophenyl)-2-{4-[(S)-(4-chlorophenyl)(phenyl) methyl]-1-piperazinyl}ethanone in presence of acid catalyst under reflux condition. All the compounds were characterized by elemental analysis and spectral studies. The newly synthesized compounds were evaluated for their antibacterial and antifungal activity

Farmakokinetika ceftriaksona u teladi

The pharmacokinetics of ceftriaxone was determined after a single intravenous and intramuscular administration at the dose rate of 10 mg/kg in crossbred cow calves. The drug concentration in plasma was quantified through High Performance Liquid Chromatography with UV detection. Following intravenous administration the drug was rapidly distributed (t1/2α: 0.13 ± 0.01 h; Vd(area); 0.44 ± 0.07 L/kg) and eliminated (t1/2β: 1.58 ± 0.06 h) from the body with a clearance rate of 3.15 ± 0.41 mL/min/kg. Following intramuscular administration, the peak plasma drug concentration (Cmax) was 15.34 ± 2.39 μg/mL at 0.25 hours (Tmax) suggesting very rapid absorption. The drug was extensively distributed (Vd(area): 1.16 ± 0.15 L/kg) and slowly eliminated (t1/2β: 5.02 ± 0.51 hours; Cl(B): 2.71 ± 0.29 mL/min/kg) following intramuscular administration. The absolute bioavailability of ceftriaxone was 47.0 ± 5.0% following intramuscular injection. However, it can be used at a dosage of 10 mg/kg intramuscularly, repeated at twelve-hourly intervals, for the treatment of susceptible bacteria infections in calves.Farmakokinetika ceftriaksona određivana je u križane teladi nakon njegove jednokratne intravenske i intramuskularne primjene u dozi od 10 mg/kg. Koncentracija lijeka u plazmi određivana je tekućinskom kromatografifi jom visokog učinka s UV zrakama. Raspodjela lijeka bila je brza nakon intravenske primjene (t1/2α: 0,13 ± 0,01 h; Vd(area): 0,44 ± 0,07 L/kg), a izlučivanje (t1/2β: 1,58 ± 0,06 h) iz tijela s klirensom od 3,15 ± 0,41 mL/min/kg. Nakon intramuskularne primjene vršna koncentracija u plazmi iznosila je (Cmax) 15,34 ± 2,39 μg/mL tijekom 0,25 sati (Tmax) što upućuje na vrlo brzu apsorpciju. Raspodjela lijeka bila je izrazito dobra (Vd(area) 1,16 ± 0,15 L/kg), a izlučivanje sporo (t1/2β: 5,02 ± 0,51 sati; Cl(B): 2,71 ± 0,29 mL/min/kg) nakon intramuskularne primjene. Apsolutna biološka raspoloživost nakon intramuskularne primjene ceftriaksona iznosila je 47,0 ± 5,0%. Međutim, on se može rabiti u dozi od 10 mg/kg i.m. te ponavljati u razmacima od 12 sati radi liječenja bakterijskih zaraza u teladi

Termoreverzibilni mukoadhezivni in situ hidrogel za oftalmičku primjenu: dizajniranje i optimizacija koristeći kombinaciju polimera

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 32 full factorial design was employed with two polymers Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 3336 ºC. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Cilj rada bio je razvoj i optimizacija termoreverzibilnog sustava za isporuku lijekova koji gelira in situ. Sustav je napravljen na bazi Pluronic F 127, a sadrži moksifloksacin hidroklorid kao modelni lijek. U radu je primjenjeno 32 potpuno faktorijsko dizajniranje s dva polimera, Pluronic F 68 i Gelrite kao nezavisnim varijablama koji su kombinirani s Pluronic F 127. Kao zavisne varijable odabrane su temperatura geliranja, čvrstoća gela, jačina bioadhezije, viskoznost i in vitro oslobađanje lijeka nakon 1 i 10 h. Pronađeno je da Pluronic F 68 u kombinaciji s Pluronic F 127 ima značajan učinak na temperaturu geliranja u rasponu od 33 do 36 C. S druge strane, Gelrite ima povoljan učinak na jačinu bioadhezije, čvrstoću gela i oslobađanje lijeka. Razvijen je kvadratni matematički model pomoću kojeg se može predvidjeti temperatura geliranja, čvrstoća gela, jačina bioadhezije i oslobađanje ljekovite tvari

Peningkatan Prestasi Belajar CAD Mahasiswa Teknik Otomotif Non-Reguler FT UNY melalui Pembuatan “Pohon Kata” Perintah dalam Program AutoCAD

Penelitian ini bertujuan meningkatkan prestasi belajar mata kuliah Computer Aided Design (CAD) mahasiswa prodi Teknik Otomotif Non-Reguler yang dinyatakan dalam bentuk rerata nilai akhir semester yang berasal dari komponen nilai tugas harian, nilai ujian tengah semester dan nilai ujian akhir semester. Penelitian quasi-eksperimen ini terdiri dari tahapan penelitian diawali dengan penyusunan materi pembelajaran sejumlah pokok bahasan tertentu dalam satu job sheet (lembar kerja), dilanjutkan dengan pembuatan bantuan “Pohon Kata” perintah dalam Auto CAD kepada kelas eksperimen yang ditentukan secara random dari dua kelas peserta kuliah Auto CAD pada Semester Genap 2008/2009. Kedua kelas diamati prestasinya, baik kecepatan penyelesaiannya maupun kualitas kebenaran gambarnya. Prestasi belajar kedua kelas juga diukur melalui pemberian ujian tengah semester dan ujian akhir semester. Setelah data prestasi kedua kelas terkumpul dilanjutkan dengan analisis statistik melalui uji beda (t-test) setelah sebelumnya dilakukan uji persyaratan analisis yang ternyata dapat dipenuhi. Hasil penelitian ini disimpulkan bahwa: prestasi belajar CAD mahasiswa pada kelas yang diberi perlakuan strategi pembelajaran menggunakan “Pohon Kata” perintah dalam Program Auto CAD lebih baik dibanding prestasi belajar CAD mahasiswa pada kelas yang tidak diberi perlakuan (75,41>70,89), dengan demikian pembelajaran CAD menggunakan media “Pohon Kata” perintah dalam Program Auto CAD dapat meningkatkan prestasi belajar mahasiswa Teknik Otomotif Program Non-Reguler

Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the β-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies

Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors

The growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human β-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity β-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of -9.53 and -8.46 as an antagonist of functional β2- and β1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human β2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent β2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]-butan-2-ol (ICI 118551) (J. Cardiovasc. Pharmacol. 1983, 5, 430-437.

Synthesis and in vitro and in vivo characterization of highly β1-Selective β-Adrenoceptor partial agonists

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),1 a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1’s aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of −7.75 and −5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1- selectivity

Weaving indigenous agricultural knowledge with formal education to enhance community food security : school competition as a pedagogical space in rural Anchetty, India

In communities from the remote rural regions of Anchetty, young learners’ informal learning experiences often come through interactions with local agriculture and the environment in which they and their families work and learn. These informal learning experiences are essential to what are otherwise called ‘indigenous knowledge systems’. For primary school students in Anchetty, the ways in which they engage in learning community-based agricultural knowledge are challenged by school-based formal education processes. Using a school competition as a pedagogical strategy for integrative space, this paper supports and explores the meaning and characteristics of indigenous agricultural knowledge (IAK)