Učinak pretkondicioniranja piperinom na farmakokinetiku peroralno primijenjenog marbofloksacina u štakora

The present study was carried out to evaluate the effect of piperine pre-conditioning on the pharmacokinetics of marbofloxacin in Wistar rats. Marbofloxacin was administrated at a dose rate of 5 mg/kg body weight alone, and along with piperine pre-conditioning at a dose of 10 mg/kg of body weight, orally for 5 days in Wistar rats. The mean values of the half-life (t1⁄2β), maximum drug concentration (Cmax) and area under the curve (AUC) were 1.19 ± 0.17 h, 2.71 ± 0.09 μg/mL and 12.25 ± 0.77 μg.h/mL, respectively, in piperine pretreated rats. The values were significantly higher than the values observed in rats administered with marbofloxacin alone (1.12 ± 0.31 h, 2.28 ± 0.20 μg/mL and 9.24 ± 0.59 μg.h/mL, respectively). The drug clearance (ClB) in piperine pretreated rats was 0.04 ± 0.02 L/h/kg, which was significantly lower than the clearance rate of the drug (0.53 ± 0.03 L/h/kg) in the animals administered with marbofloxacin alone. The study reveals that piperine has a significant effect on the pharmacokinetics of marbofloxacin, which may be due to an increase in the drug absorption and inhibition of elimination of the drug in rats.U ovom je radu istražen učinak pretkondicioniranja piperinom na farmakokinetiku marbofloksacina Wistar štakora. Marbofloksacin je apliciran u dozi od 5 mg/kg tjelesne mase peroralno, samostalno i nakon pretkondicioniranja piperinom u dozi od 10 mg/kg tjelesne mase peroralno tijekom 5 dana. U štakora tretiranih piperinom prosječne vrijednosti poluživota (t1⁄2β) bile su 1,19 ± 0,17 h, maksimalna koncentracija lijeka (Cmax) 2,71 ± 0,09 μg/mL, a površina ispod krivulje (AUC) 12,25 ± 0,77 μg.h/mL. Navedene vrijednosti bile su znakovito više od onih utvrđenih u štakora tretiranih samo marbofloksacin (1,12 ± 0,31 h, 2,28 ± 0,20 μg/mL i 9,24 ± 0,59 μg.h/mL). Klirens lijeka (ClB) u štakora tretiranih piperinom bio je 0,04 ± 0,02 L/h/kg što je bilo znakovito niže od klirensa lijeka (0,53 ± 0,03 L/h/ kg) u životinja koje su dobivale samo marbofloksacin. Ovo istraživanje pokazuje da piperin znakovito utječe na farmakokinetiku marbofloksacina, što može biti posljedica povećane apsorpcije lijeka i inhibicije uklanjanja lijeka u štakora

A study of evaluation of various risk factors of retinal vein occlusion

Background:A study of various ocular & systemic risk factors in Retinal Vein Occulation (RVO) at tertiary eye care centre.Methods:A prospective study included 50 eyes of 50 patients, in period of September 2010 to August 2012. Inclusion criteria: 1. Age >25 years, 2. All newly diagnosed cases of vein occlusion. Exclusion criteria: 1. Age <25 years 2. All other ocular diseases causing significant visual impairment. A detailed history, ophthalmic & systemic examinations with all necessary investigations-as and when required were done.Results: In our study, RVOs were more common in males – 26 (52%) & in 56-65 years of age group - 16 (32%). BRVO (Branch Retinal Vein Occlusion)s were more common than CRVO (Central Retinal Vein Occlusion) - Nonischemic (26%) >Ischemic (24%). In risk factors - most common was hypertension - in 38 (76%) patients. Followed by descending order, hyperlipidemia 27 (54%) >diabetes mellitus 16 (32%) >tobacco 14 (28%) >hyper homocystinemia 4 (8%) >severe alcohol 2 (4%). The complications were more in ischemic than Nonischemic-CRVO >BRVO - they were macular edema 43 (86%) >neovascularization at iris - 14 (28%) >neovascularization at angle - 10 (20%) >neovascular glaucoma – 4 (8%). Conclusion:RVOs are more common with increasing age, in males & most common risk factor is hypertensive. Most common cause for vision loss is macular edema - ischemic >non-ischemic.

Surface-enhanced Raman spectroscopy of the endothelial cell membrane

We applied surface-enhanced Raman spectroscopy (SERS) to cationic gold-labeled endothelial cells to derive SERS-enhanced spectra of the bimolecular makeup of the plasma membrane. A two-step protocol with cationic charged gold nanoparticles followed by silver-intensification to generate silver nanoparticles on the cell surface was employed. This protocol of post-labelling silver-intensification facilitates the collection of SERS-enhanced spectra from the cell membrane without contribution from conjugated antibodies or other molecules. This approach generated a 100-fold SERS-enhancement of the spectral signal. The SERS spectra exhibited many vibrational peaks that can be assigned to components of the cell membrane. We were able to carry out spectral mapping using some of the enhanced wavenumbers. Significantly, the spectral maps suggest the distribution of some membrane components are was not evenly distributed over the cells plasma membrane. These results provide some possible evidence for the existence of lipid rafts in the plasma membrane and show that SERS has great potential for the study and characterization of cell surfaces

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes