EFFECTS OF FASTING ON PRAVASTATIN DISPOSITION IN PERFUSED RAT LIVER

Objective: Various nutrients such as glucose and cholesterol affect the expression of hepatic transporters. Although the pharmacokinetics of some drugs is affected by fasting, the fasting effects on drug hepatic disposition via alterations in transporters are unclear. Organic anion-transporting polypeptides and multidrug resistance-associated protein 2 (Mrp2/Abcc2) expressed in the liver are involved in hepatic disposition of pravastatin.Methods: An in situ perfused rat liver system was established. The mRNA and protein levels of transporters in the liver were examined by real-time reverse transcription PCR and western blotting. The localization of Mrp2 in hepatocytes was determined by immunostaining.Results: Pravastatin was rapidly eliminated from the perfusate. The cumulative biliary excretion amounts of pravastatin in fasting rats were significantly lower from 10 min compared with control. In fasting rats, the area under the plasma concentration-time curve (AUC)0‒∞ of pravastatin in the perfusate was significantly decreased, and hepatic clearance (CLh) and hepatic corrected clearance (CLcor) were significantly increased. The biliary clearance (CLbile) in fasting rats tended to decrease compared with that in control rats. Protein expression levels of transporters were unchanged after fasting. Confocal microscopy revealed a disruption of Mrp2 and ZO-1 colocalization in the liver of fasting rats.Conclusion: The biliary excretion of pravastatin was inhibited by fasting via decreased Mrp2 localization on the canalicular membrane

Inferior displacement of the lower eyelid during intraoperative quantification in blepharoptosis surgery

Hirohiko Kakizaki, Yasuhiro Takahashi, Masahiro Zako, Masayoshi IwakiDepartment of Ophthalmology, Aichi Medical University, Nagakute, Aichi, JapanPurpose: To examine inferior displacement of the lower eyelid during eye closing in intraoperative quantification of blepharoptosis surgery.Methods: A series of lower eyelid movements during eye closing in intraoperative quantification of blepharoptosis surgery were examined in 30 eyelids of 15 patients (6 males and 9 females; mean age 70.0 years; range 43–81 years) with bilateral aponeurotic blepharoptosis.Results: Inferior displacement of the lower eyelid was observed in all eyelids examined, although the extent varied in each patient (range 2.0–4.5 mm; mean 3.2 mm). Inferior displacement occurred with upward eye movement caused by Bell's phenomenon. Many wrinkles were simultaneously observed as a result of contraction of the orbicularis oculi muscle. After maintaining the inferiorly displaced state for several seconds, 20 lower eyelids in 10 patients naturally moved superiorly to a resting position. On the other hand, 10 lower eyelids in 5 patients remained in the same inferior position for more than 5 seconds, after which we had to manually elevate them to a resting position. The eyes then moved inferiorly to their resting position with a decrease in the number of lower eyelid wrinkles. Once the patients opened their eyes, inferior displacement of the lower eyelid completely disappeared.Conclusions: Inferior displacement of the lower eyelid during eye closing increases the amount of lagophthalmos. This phenomenon needs to be considered for quantifying the intraoperative lagophthalmos level during blepharoptosis surgery.Keywords: blepharoptosis surgery, eye closing, inferior displacement, intraoperative quantification, lower eyelid&nbsp

Effect of oral tranexamic acid on macular edema associated with retinal vein occlusion or diabetes

Purpose: Tranexamic acid (TXA) is a widely used antifibrinolytic agent that can also cause a decrease in vascular permeability. We hypothesized that TXA could improve macular edema (ME) that is caused by an increase in retinal vascular permeability. The aim of this study is to evaluate the efficacy of oral TXA for ME associated with retinal vein occlusion (RVO) or diabetic ME (DME).Patients and methods: Oral TXA (1,500 mg daily for 2 weeks) was administered to patients with persistent ME secondary to RVO (7 eyes) and DME (7 eyes). After 2 weeks (ie, the final day of administration) and 6 weeks (ie, 4 weeks after the final administration), best-corrected visual acuity and central macular thickness (CMT) were measured and compared with baseline. Analyses were performed for RVO and DME cases. No other treatment was performed during the study period.Results: In RVO cases, significant improvement in CMT was found between baseline (467.7±121.4 µm) and 2-week measurements after treatment (428.7±110.5 µm, p=0.024). No significant change was found in CMT between measurements taken at baseline and 6 weeks after treatment. In DME cases, no significant change was found in CMT between measurements taken at baseline and 2 or 6 weeks after treatment. In all analyses of best-corrected visual acuity, no significant change was observed.Conclusion: The results support the hypothesis that plasmin plays a role in the development of ME associated with RVO, and oral TXA administration may be useful as an adjuvant treatment when combined with other agents such as anti-vascular endothelial growth factor

Ocular parameters before and after steep Trendelenburg positioning for robotic-assisted laparoscopic radical prostatectomy

Purpose: Intraocular pressure (IOP) increases in patients in a steep Trendelenburg position during robotic-assisted laparoscopic radical prostatectomy (RALP). We hypothesized that a steep Trendelenburg position during RALP, an unusual systemic condition involving a transiently increased IOP, may induce ocular pathology that can be detected by detailed evaluations long after the surgery. This study aims to explore ocular structural and functional parameters in patients before and in the long term after the surgery.Patients and methods: A comparative observational study was performed. A total of 44 eyes of 22 male patients scheduled for RALP at Aichi Medical University from August 2012 to July 2013 were included. Clinical parameters before and after RALP were compared. Peri­operative IOP was measured immediately post-induction of anesthesia in the flat supine position (T1), immediately post-steep Trendelenburg position (T2), and prior to returning to a flat supine position while in a steep Trendelenburg position (T3). The thicknesses of the peripapillary retinal nerve fiber layer, ganglion cell complex (GCC), and central fovea were measured with spectral domain optical coherence tomography. Humphrey perimetry was performed before and at 3 and 6 months after surgery.Results: The average IOPs (mmHg) at each stage were T1=10.4, T2=21.7, and T3=29.6, and differed significantly. The mean visual acuity (logarithm of the minimal angle of resolution), IOP, mean deviation, and pattern standard deviation measured by the Humphrey field analyzer showed no statistically significant difference before and after surgery. The ganglion cell complex and retinal nerve fiber layer thicknesses measured at each location and the central fovea thicknesses measured before and after surgery did not differ significantly.Conclusion: No significant disorders in ocular structural and functional parameters were found until long after RALP

Effect of Ninjin’yoeito on the Loss of Skeletal Muscle Function in Cancer-Bearing Mice

Ninjin’yoeito (NYT), a traditional Japanese Kampo medicine formula, is used as a remedy for conditions, and physical weakness. Cancer cachexia is seen in advanced cancer patients and is defined by an ongoing loss of skeletal-muscle mass that leads to progressive functional impairment. In the present study, we examined the hypothesis whether NYT improves the functional loss of skeletal muscle cancer cachexia. Male C57/BL 6J mice with B16BF6 melanoma tumor showed decreased expression of myosin heavy chain (MHC) in the gastrocnemius muscle. Moreover, the expression of SOCS3 and phosphorylated STAT3 and AMPK was increased, and the expression of phosphorylated 4E-BP1 was decreased in the gastrocnemius muscle of tumor-bearing mice. These data suggested that amino acid metabolism was altered in tumor-bearing mice, which were normalized by the NYT intervention. The present study showed that NYT might be a novel therapeutic option for the treatment of sarcopenia occurring cancer cachexia