Uterine preservation with Cho suture in localized multifocal atonicity of uterus with failed medical management and uterine tamponade

Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality, and one of the common obstetrical emergencies. Quite commonly, it occurs in patients where PPH is not expected. Management has to be swift and precise according to the steps and the response initiated by the uterine musculature during the management. In our patient, we had a localized multifocal atony of the uterus, at points where the uterine sinuses were bleeding due to atony, and medical management and uterine tamponade failed, with a raised D-dimer level. As the stepwise management failed with uterine devascularisation failing to control PPH, a decision for uterine compression suture (UCS), Cho suture was taken

Farmakokinetika eprinomektina u ovaca nakon potkožne primjene.

The pharmacokinetics of eprinomectin was determined in lactating sheep following subcutaneous administration at a dose rate of 0.2 mg kg-1. The eprinomectin concentration in plasma was determined using High Performance Liquid Chromatography (HPLC) with a fluorescence detector. The kinetics of plasma concentrations were analysed using the non-compartment model. The maximum plasma concentration of 24.44 ng/mL occurred 2 days post-administration. Following subcutaneous administration of eprinomectin in sheep, the value of plasma elimination half-life, the area under the plasma concentration time curve (AUC) and mean residence time (MRT) were 388.52 ± 0.25 h. 4282.10 ng.h/mL and 374.50 h, respectively. The values of V (area), Vd(ss) and Cl(B) were 20.50 mL/kg, 13.70 mL/kg and 0.04 mL/h/kg, respectively. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and longer mean residence time with a lower dose than a pour-on application, and that an injectable formulation may be applied in lactating sheep with zero withdrawal period.Farmakokinetika eprinomektina određivana je u ovaca u laktaciji nakon potkožne primjene u dozi od 0,2 mg/kg. Njegova koncentracija u plazmi utvrđena je visoko učinkovitom tekućinskom kromatografijom s fluorescentnim detektorom. Kinetika koncentracija u plazmi analizirana je na osnovi modela bez odjeljaka. Najveća koncentracija u plazmi od 24,44 ng/mL dokazana je dva dana nakon primjene. Poluživot eliminacije iz plazme iznosio je 388,52 ± 0,25 sati, površina ispod krivulje koncentracije u plazmi (AUC) 4282,10 ng/h/mL, a prosječno vrijeme zadržavanja iznosilo je 374,50 sati. Vrijednost prividnog volumena raspodjele, Vd(area), iznosila je 20,50 mL/kg, prosječni vidljivi volumen raspodjele, Vd(ss), 13,70 mL/kg, a ukupni klirens 0,04 mL/sat/kg. Istraživanje je pokazalo da potkožna primjena eprinomektina pruža veću bioraspoloživost, duže vrijeme zadržavanja s manjom dozom u odnosu na veliku te da se injekcijska formulacija može primijeniti u ovaca u laktaciji

Priprava i karakterizacija čvrstih disperzija etorikoksiba s polietilenglikolom 4000 i polivinilpirolidonom K30

The objective of the present investigation was to study the influence of polyethylene glycol 4000 (PEG) and polyvinylpyrrolidone K30 (PVP) on in vitro dissolution of etoricoxib from solid dispersions. The preliminary studies were carried out using physical mixture of drug and carriers. The solid dispersions were prepared using the solvent evaporation method. A 32 factorial design was adopted in the solvent evaporation method using the concentration of PEG and PVP as independent variables. Full and reduced models were evolved for dependant variables, such as the percentage of drug release in 10 min (Q10), percentage of drug release in 30 min (Q30), percentage of drug release in 45 min (Q45) and percent dissolution efficiency (DE). The reduced models were validated using two check points. Q10 > 65%, Q30 > 75%, Q45 > 85% and DE > 80% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependant variables. PEG was found to be more effective in increasing the drug dissolution compared to PVP. Wettability study was carried out for pure drug and optimized batch. FT-IR spectroscopy, microscopic study, differential scanning calorimetry and X-ray diffraction study were carried out in order to characterize drug in the solid dispersions. Improved dissolution was attributed to decreased crystallinity of the drug, improved wetting and solubilizing effects of carriers such as PEG and PVP from the solid dispersion of etoricoxib. In conclusion, dissolution of etoricoxib can be modulated using appropriate levels of hydrophilic carriers.U radu je proučavan utjecaj polietilenglikola 4000 (PEG) i polivinilpirolidona K30 (PVP) na in vitro oslobađanje etorikoksiba iz čvrstih disperzija. Preliminarni pokusi provedeni su sa smjesom ljekovite tvari i polimernih nosača. Čvrste disperzije pripravljene su metodom uparavanja otapala. Za ovu metodu razvijen je 32 faktorijalni dizajn koristeći koncentraciju PEG i PVP kao nezavisne varijable. Za zavisne varijable razvijeni su potpuni i reducirani modeli, kao što su postotak oslobođene ljekovite tvari u 10 (Q10), 30 (Q30) ili 45 minuta (Q45) i postotak učinkovitosti oslobađanja (DE). Reducirani modeli su validirani pomoću dviju kontrolnih točaka. Q10 > 65%, Q30 > 80%, Q45 > 85% i DE > 80% su upotrebljeni kao ograničenja za izbor optimirane serije. Prikazane su konturne linije za pojedine zavisne varijable. Oslobađanje lijeka bilo je učinkovitije iz pripravaka s PEG-om. Vlaženje je proučavano za čistu ljekovitu supstanciju i omptimiranu seriju. Za karakterizaciju ljekovite tvari u čvrstim disperzijama korištene su FT-IR spektroskopija, mikroskopske studije, diferencijalna pretražna kalorimetrija i difrakcija rentgenskim zrakama. Povećano oslobađanje posljedica je smanjene kristaliničnosti ljekovite tvari, pojačanog vlaženja i solubilizacijskog učinka polimernih nosača u disperzijama. Može se zaključiti da se oslobađanje etorikoksiba može modulirati promjenom količine hidrofilnih nosača

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

Priprava kompleksa etorikoksiba s β-ciklodekstrinom metodom gnječenja i njihova karakterizacija

The binary system of etoricoxib with β-cyclodextrin (β-CD) was prepared by the kneading method. Drug-cyclodextrin interactions in solution were investigated by the phase solubility analysis. Differential scanning calorimetry, infrared spectroscopy, powder X-ray diffractometry and microscopic study were used to characterize the solid state of all binary systems, whereas their dissolution properties were evaluated according to the USP XXIII paddle method. The results indicate partial interaction of the drug with β-CD in the physical mixture and complete interaction in the kneaded complex. The dissolution of etoricoxib was notably increased as compared to pure drug as well as its physical mixture. The complex showed more than 75% drug released in 30 min.Metodom gnječenja pripravljen je binarni sustav etorikoksiba s β-ciklodekstrinom (β-CD). Tijekom 30 minuta iz kompleksa se oslobodilo više od 75% ljekovite tvari, što je značajno više u odnosu na fizičku smjesu etorikoksiba i β-CD ili na čistu ljekovitu tvar. Interakcije lijeka i ciklodekstrina u otopini ispitivane su analizom fazne topljivosti. Za karakterizaciju čvrstog stanja svih binarnih sustava korišteni su diferencijalna pretražna kalorimetrija, infracrvena spektroskopija, difrakcija rentgenskih zraka na praškastom uzorku i mikroskopija. Oslobađanje je praćeno metodom lopatice prema USP XXIII. Rezultati ukazuju na djelomičnu interakciju ljekovite tvari s β-CD u fizičkoj smjesi i potpunu interakciju u kompleksu

Farmakokinetika eprinomektina u ovaca nakon potkožne primjene.

The pharmacokinetics of eprinomectin was determined in lactating sheep following subcutaneous administration at a dose rate of 0.2 mg kg-1. The eprinomectin concentration in plasma was determined using High Performance Liquid Chromatography (HPLC) with a fluorescence detector. The kinetics of plasma concentrations were analysed using the non-compartment model. The maximum plasma concentration of 24.44 ng/mL occurred 2 days post-administration. Following subcutaneous administration of eprinomectin in sheep, the value of plasma elimination half-life, the area under the plasma concentration time curve (AUC) and mean residence time (MRT) were 388.52 ± 0.25 h. 4282.10 ng.h/mL and 374.50 h, respectively. The values of V (area), Vd(ss) and Cl(B) were 20.50 mL/kg, 13.70 mL/kg and 0.04 mL/h/kg, respectively. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and longer mean residence time with a lower dose than a pour-on application, and that an injectable formulation may be applied in lactating sheep with zero withdrawal period.Farmakokinetika eprinomektina određivana je u ovaca u laktaciji nakon potkožne primjene u dozi od 0,2 mg/kg. Njegova koncentracija u plazmi utvrđena je visoko učinkovitom tekućinskom kromatografijom s fluorescentnim detektorom. Kinetika koncentracija u plazmi analizirana je na osnovi modela bez odjeljaka. Najveća koncentracija u plazmi od 24,44 ng/mL dokazana je dva dana nakon primjene. Poluživot eliminacije iz plazme iznosio je 388,52 ± 0,25 sati, površina ispod krivulje koncentracije u plazmi (AUC) 4282,10 ng/h/mL, a prosječno vrijeme zadržavanja iznosilo je 374,50 sati. Vrijednost prividnog volumena raspodjele, Vd(area), iznosila je 20,50 mL/kg, prosječni vidljivi volumen raspodjele, Vd(ss), 13,70 mL/kg, a ukupni klirens 0,04 mL/sat/kg. Istraživanje je pokazalo da potkožna primjena eprinomektina pruža veću bioraspoloživost, duže vrijeme zadržavanja s manjom dozom u odnosu na veliku te da se injekcijska formulacija može primijeniti u ovaca u laktaciji

In vitro i in vivo protuupalna, antibakterijska i farmakokinetička svojstva baikaleina

Baicalein is a bioactive flavone originally isolated from the roots of Scutellaria baicalensis, Scutellariala teriflora and Oroxylum indicum. The in vitro and in vivo anti-inflammatory and antibacterial properties of baicalein and pharmacokinetics after its single intramuscular administration were studied in Wistar rats. The in vitro anti-inflammatory activity of baicalein (10, 50 and 100 µM) was tested for its ability to inhibit the COX-2 enzyme by measuring PGE2 levels and determination of nitric oxide (NO) production in lipopolysaccharide (LPS) treated RAW 264.7 macrophage cells, in which baicalein was found to have significant inhibition of NO and PGE2 production in RAW 264.7 macrophage cells as compared with the LPS control group. The in vivo anti-inflammatory activity of baicalein (200 mg/kg) was assessed using the carrageenan-induced rat paw oedema model, following intramuscular injection. A significant percentage of inhibition of oedema volume was observed when compared with the carrageenan control group. In vitro and in vivo antibacterial activities of baicalein were determined by the micro broth dilution technique and neutropenic rat thigh infection model, wherein baicalein did not show any antibacterial property. Concentrations of baicalein were determined in rat plasma by high performance liquid chromatography (HPLC) after a single intramuscular administration at a dose of 200 mg/kg body weight, in which the mean peak plasma drug concentration (Cmax) of 0.77 ± 0.02 μg/mL was achieved at 0.08 h. The mean elimination half-life (t½β), the apparent volume of distribution (Vd(area)), total body clearance (Cl(B)) and mean residence time (MRT) were observed as 0.63 ± 0.06 h, 601.03 ± 28.18 L/kg, 677.39 ± 35.36 L/h/kg and 0.76 ± 0.06 h, respectively. Conclusively, in the present study, baicalein did not show in vitro or in vivo antibacterial property, but proved to have good anti-inflammatory activity. The available anti-inflammatory drugs have proved to have side effects in veterinary and human therapeutics. In this situation, baicalein may become an effective alternative to non-steroidal anti-inflammatory drugs and should also be studied in target animal species. Further research should be carried out to improve the solubility and bioavailability of baicalein through injectable routes.Baikalein je bioaktivni flavon izvorno izoliran iz korijena biljaka Scutellaria baicalensis, Scutellariala teriflora i Oroxylum indicum. U ovom su radu istraživana in vitro i in vivo protuupalna i antibakterijska svojstva baikaleina te farmakokinetika nakon njegove pojedinačne intramuskularne primjene u wistar štakora. In vitro protuupalno djelovanje baikaleina (10, 50 i 100 µM) analizirano je s obzirom na sposobnost inhibicije enzima COX-2 mjerenjem razine PGE2 i određivanjem proizvodnje dušikova oksida (NO) u makrofagnim stanicama RAW 264,7 tretiranim lipopolisaharidom (LPS). Ustanovljeno je da baikalein znakovito inhibira proizvodnju NO i PGE2 u makrofagnim stanicama RAW 264,7 u usporedbi s LPS kontrolnom skupinom. In vivo protuupalno djelovanje baikaleina (200 mg/ kg) procijenjeno je pomoću modela za mjerenje edema šape nakon intramuskularne injekcije karagenana, te je uočena znakovita inhibicija volumena edema u usporedbi s kontrolnom skupinom. In vitro i in vivo antibakterijsko djelovanje baikaleina određeno je metodom razrjeđivanja mikrobujona te modelom infekcije bedra neutropeničnog štakora, pri čemu baikalein nije pokazao antibakterijska svojstva. Koncentracije baikaleina utvrđene su u plazmi štakora tekućinskom kromatografijom visoke djelotvornosti (HPLC) nakon pojedinačne intramuskularne primjene u dozi od 200 mg/kg tjelesne mase u kojoj je prosječna vršna koncentracija lijeka (Cmax) bila 0,77 ± 0,02 μg/mL, a postignuta je za 0,08 h. Prosječan poluživot eliminacije (t½β) bio je 0,63 ± 0,06 h, providni volumen distribucije (Vd(površina)) 601,03 ± 28,18 L/kg, ukupni tjelesni klirens (Cl(B)) 677.39 ± 35.36 L/h/kg, a prosječno vrijeme zadržavanja (MRT) 0,76 ± 0,06 h. Zaključeno je da u ovom istraživanju baikalein nije pokazao in vitro i in vivo antibakterijska svojstva, ali je pokazao dobro protuupalno djelovanje. S obzirom na to da dostupni protuupalni lijekovi imaju nuspojave u liječenju ljudi i životinja, baikalein bi mogao biti učinkovita alternativa nesteroidnim protuupalnim lijekovima te bi ga trebalo istražiti i kod ciljanih životinjskih vrsta. Potrebna su daljnja istraživanja kojima bi se poboljšala topljivost i bioraspoloživost baikaleina injekcijskom primjenom

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

Plutajuće matriks tablete: Dizajniranje i optimizacija kombiniranjem polimera

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.Cilj rada bio je razvoj i optimizacija plutajućih sustava za isporuku lijekova u želucu (GFDDS) s domperidonom kao modelom lijeka. Box-Behnkenovo dizajniranje korišteno je u formuliranju GFDDS. Nezavisne varijable u dizajniranju bila su tri polimera: hidroksipropil metilceluloza K4M (HPMC K4M) (X1), Carbopol 934P (X2) i natrijev alginat (X3), a zavisne varijable usporeno vrijeme plutanja (FLT), ukupno vrijeme plutanja (TFT), vrijeme potrebno za oslobađanje 50% lijeka (t50) i difuzijski eksponent (n). Pripravljeno je ukupno sedamnaest formulacija. Analizirani su podaci o oslobađanju ljekovite tvari. Količina HPMC značajno utječe na svojstva plutanja, dok količina karbopola ima negativni učinak na svojstvo plutanja, ali kontrolira oslobađanje ljekovite tvari. Natrijev alginat nema značajni učinak na svojstva plutanja, ali utječe na stvaranje gela. Kvadratni matematički model može se upotrijebiti za predviđanje formulacija sa željenim profilom oslobađanja i svojstvima plutanja

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