[Preliminary study of Boston keratoprosthesis in treatment of severe late stage ocular chemical burns].

OBJECTIVE: To evaluate preliminary clinical outcome of Boston type I keratoprosthesis in ocular chemical burn patients. METHODS: Six keratoprosthesis were implanted into 6 patients of bilateral blindness. Visual acuity in these patients before the operation was light perception and all of them were unsuitable for standard penetrating corneal transplantation. The causes for corneal opacity were alkali burn in 2, sulfate acid burn in 3 and ethanol injury in 1 patient. Shirmer's test revealed severe dry eye in 3 patients, only one eye had normal lacrimal secretion. All patients were male, with follow-up period ranged from 17 to 26 months (mean 24 months). RESULTS: The postoperative visual acuity ranged from 0.05 to 0.5, 5 of them was better than 0.1. The retention rate within the follow-up period was 100%. Intraocular pressure was in normal limit, no retinal detachment was detected by type B ultrasonic examination. Postoperatively, retro-keratoprosthestic membrane occurred in 2 cases and was treated with YAG laser membranectomy, one eye complicated with elevated intraocular pressure and treated with shunt implantation. CONCLUSION: The Boston type 1 keratoprosthesis is a viable option for patients with obsolete chemical burns.

Ocular safety and pharmacokinetics study of FK506 suspension eye drops after corneal transplantation.

PURPOSE: The aim of this study was to investigate the sensitization, pharmacokinetics, and absorption of FK506 after corneal transplantation. METHODS: New Zealand albino rabbits were divided into normal and corneal transplantation groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose, medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup. One drop (25 µL) of FK506 was administered topically to both eyes of the rabbits 4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were sacrificed after the administration of the last dose. Both eyes were enucleated; the left eye was used for pathologic examination and the right eye for the determination of FK506 distribution. The other 5 rabbits in each subgroup were sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes were enucleated for pathologic examination and tissue distribution determination as the former 5 rabbits in each subgroup (the second batch). RESULTS: Fluorescein staining and local ocular reaction provided evidence that there were no significant differences between control and FK506-instilled eyes in the rabbit model at any of the tested doses. Histologic examination revealed no ocular abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak serum concentration (C(max)) of systemic absorption ranged from 4.31±0.79 ng/mL to 14.89±6.85 ng/mL. CONCLUSION: Our study suggests that up to 0.1% FK506 administered 4 times a day (q.i.d.) topically is safe for the rabbit eye. However, further safety studies are required in view of systemic adverse effects.

Different mechanisms of cis-9,trans-11- and trans-10,cis-12- conjugated linoleic acid affecting lipid metabolism in 3T3-L1 cells.

Conjugated linoleic acid (CLA) has been shown to reduce body fat mass in various experimental animals. It is valuable to identify its influence on enzymes involved in energy expenditure, apoptosis, fatty acid oxidation and lipolysis. We investigated isomer-specific effects of high dose, long treatment of CLA (75.4 µmol/L, 8 days) on protein and gene expression of these enzymes in cultured 3T3-L1 cells. Proteomics identified significant up- or down-regulation of 52 proteins by either CLA isomer. Protein and gene expression of uncoupling protein (UCP) 1, UCP3, perilipin and peroxisome proliferator-activated receptor (PPAR) α increased whereas UCP2 reduced for both CLA isomers. And eight-day treatment of trans-10,cis-12 CLA, but not cis-9,trans-11 CLA, significantly up-regulated protein and mRNA levels of PKA (P<.05), CPT-1 and TNF-α (P<.01). Compared to protein expression, both isomers did not significantly influence the mRNA expression of HSL, ATGL, ACO and leptin. In conclusion, high-dose, long treatment of cis-9,trans-11 CLA did not promote apoptosis, fatty acid oxidation and lipolysis in adipocytes, but may induce an increase in energy expenditure. trans-10,cis-12 CLA exhibited greater influence on lipid metabolism, stimulated adipocyte energy expenditure, apoptosis and fatty acid oxidation, but its effect on lipolysis was not obvious.

Preparation of 0.05% FK506 suspension eyedrops and its pharmacokinetics after topical ocular administration.

PURPOSE: To investigate the stability of FK506 eye suspension and its pharmacokinetics in rabbit aqueous humor, as well as its distribution in eye tissues. METHODS: Sedimentation rate, flocculation value, redispersion time, rheological study, and accelerated experiment were determined for evaluating the stability of FK506 suspension. In a single-dose pharmacokinetic study, six rabbits were instilled a 25-microL drop of 0.05% FK506 suspension and aqueous humor samples were collected at different intervals after administration. In a multiple-dose pharmacokinetic study, a 25-microL drop of FK506 suspension was instilled into the right eye of six rabbits four times a day for 7 days. On the eighth day, aqueous humor samples were collected before the administration of the first, second, third dose, and at different checkpoints after the third dose. For tissue distribution study, six eyes per time points (18 rabbits in total) were treated with single dose of FK506 suspension, and the eyes were enucleated at 60, 100, and 240 min after treatment, then eye tissues were collected. The concentrations of FK506 in all samples were determined by LC-MS/MS. RESULTS: The preliminary results indicated that the stability of FK506 suspension was in accord with the standards of Chinese pharmacopoeia. The maximum concentrations of aqueous humor after single dose and multiple dose administrations were 31.40 +/- 9.32 ng/mL and 37.73 +/- 11.25 ng/mL, respectively. The concentration of FK506 in cornea at 60, 100, and 240 min after a single dose were 402.0 +/- 96.8 ng/g, 363.8 +/- 84.5 ng/g, and 220 +/- 62.3 ng/g, respectively. Determination of pharmacokinetic parameters of single-dose and multiple-dose administration, as well as the FK506 concentrations in eye tissues, showed that the FK506 formulation and the dosing regimen ensured the therapeutic concentration of FK506 for treating corneal allograft rejection. CONCLUSIONS: Based on the stability, single-dose and multiple-dose pharmacokinetics, and tissue distribution, FK506 suspension eyedrops may be a suitable candidate for clinical application in ophthalmology.

Conjugated linoleic acid supplementation enhances antihypertensive effect of ramipril in Chinese patients with obesity-related hypertension.

BACKGROUND: Conjugated linoleic acid (CLA) refers to a group of positional and geometrical conjugated dienoic isomers of linoleic acid. Our aim was to investigate the effect of 8-week dietary CLA supplementation on blood pressure, concentrations of plasma adiponecin, leptin, and as well as angiotensin-converting enzyme (ACE) activity in obese hypertensive subjects. METHODS: Eighty obese individuals with stage 1 uncontrolled essential hypertension were randomized in a double-blind, placebo-controlled trial. Participants were randomized to a daily dose of 4.5 g/day CLA (nine 0.5-g capsules; a 50:50 isomer blend of c 9,t 11 and t 10,c 12 CLA) with 37.5 mg/day ramipril (group 1) or placebo with 37.5 mg/day ramipril (group 2) for 8 weeks. Baseline and endpoint systolic BP, diastolic BP, and concentrations of plasma adiponecin, leptin, angiotensinogen, and ACE activity were measured. RESULTS: Treatment with CLA significantly enhanced the reduction effect of ramipril on systolic BP and diastolic BP (P < 0.05). It also increased plasma adiponectin concentration (P < 0.05) and decreased plasma concentrations of leptin and angiotensinogen (P < 0.05); however, significant change was not observed in ACE activity. CONCLUSIONS: An 8-week long supplementation of CLA enhanced the effect of ramipril on blood pressure reduction in treated obese hypertensive patients. The antihypertensive effect of CLA might be related to the changed secretion of hypertensive adipocytokines in plasma.

Determination of tacrolimus in rabbit aqueous humor by liquid chromatography-electrospray ionization tandem mass spectrometry.

A simple, sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of tacrolimus (FK506) in rabbit aqueous humor. After a simple protein-precipitation by methanol, the post-treatment samples were separated on a reversed-phase, Thermo-Hypersil-BDS-C18 column with a mobile phase of a mixture of 0.1% formic acid in water, methanol and acetonitrile (5:85:10, v/v/v). Tacrolimus and ritonavir (internal standard, IS) were all detected by the selected reaction-monitoring (SRM) mode. The method developed was validated in rabbit aqueous humor with a daily working range of 0.5-100 ng/ml with correlation coefficient, r>0.99 and a sensitivity of 0.5 ng/ml as lower limit of quantification, respectively. This method was fully validated for the accuracy, precision, possible matrix effect and stability. The method proved to be accurate and specific, and was applied to the pharmacokinetic study of tacrolimus in rabbit aqueous humor.