Design and evaluation of a brinzolamide drug-resin in situ thermosensitive gelling system for sustained ophthalmic drug delivery.

In this study a brinzolamide drug-resin ophthalmic thermosensitive in situ gelling system was developed and evaluated. Brinzolamide was combined with ion exchange resins to prolong the retention time of drugs in the eye and to reduce ocular and systemic side effects. Poloxamer F127 was used as gelling vehicle in combination with carbopol 934P, which acted as a viscosity-enhancing agent. They were prepared using the cold method. The optimized formulation exhibited a sol-gel transition at 33.2±1.1°C with pseudoplastic flow behavior. This formulation was stable and nonirritant to rabbit eyes. In vitro release studies demonstrated diffusion-controlled release of brinzolamide from the combined solutions over a period of 8 h. In vivo evaluation (the elimination of brinzolamide through tears and absorption of brinzolamide in aqueous humor) indicated that the solution combination was better able to retain the drug than commercial preparations. Thus this formulation is safe for ophthalmic use and significantly increases brinzolamide bioavailability in aqueous humor.

Analysis of carbon sink of steel slag in China.

Under the context of the elevated greenhouse gases, how to reduce carbon emissions and increase carbon absorption is the focus of current research on climate change. Based on data of Chinese crude steel production from 1963 to 2016 and greenhouse gas inventory method, we established steel slag carbon sequestration calculation method. The steel slag carbon sequestration from 1963 to 2016 was estimated and the uncertainty analysis was made. The results showed that annual carbon sink of steel slag in China increased from 3.75×103 t C in 1963 to 1359.32×103 t C in 2016. The steel slag accumulative carbon sink was 15×106 t C, with about ±30.4% total uncertainty during 1963-2016. The annual carbon sink of steel slag was composed of carbon sink of the current year steel slag and the previous years. Due to the dense structure and low carbonation rate of steel slag, the carbon sink of the current year was small, accounting for 37% of the total, while that of the previous years were relatively large, accounting for 63% of the total. Although annual carbon sink of steel slag was small, the long-term accumulative carbon sink for steel slag was very considerable, which could not be ignored. Future research should refine carbonation rate of steel slag under diffe-rent environmental conditions to reduce steel slag carbon accounting uncertainty, promote the deve-lopment of carbon capture and storage (CCS) technology with steel slag as raw material to increase effective carbon sequestration, which would provide scientific support for China's international negotiations on climate change.

Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice.

BACKGROUND: The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone 8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia. METHODS: Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF. RESULTS: Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P > 0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P < 0.05); but the expression of its receptor, TrkB, was not significantly affected. CONCLUSION: These results suggested that the molarless condition impaired learning and memory abilities in SAMP8 mice three months after teeth extraction, and this effect was accompanied by significantly reduced BDNF expression in the cortex and hippocampus.

Cyclosporine treatment in idiopathic membranous nephropathy nephrotic syndrome in adults: a retrospective study spanning 15 years.

BACKGROUND: Cyclosporine is effective in treating nephrotic syndrome (NS) with idiopathic membranous nephropathy (IMN) in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse. METHODS: Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed. RESULTS: Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was (7.47 ± 3.14) g/d, serum albumin (24.50 ± 6.29) g/L, and serum creatinine (82.62 ± 21.18) mmol/L. Cyclosporine was commenced at a mean dose of (3.46 ± 0.63) mg×kg(-1)×d(-1). Oral prednisone (0.40 ± 0.29) mg×kg(-1)×d(-1) was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months (range 1 - 93 months) and stopped in non-responders by month six. By month 3 (n = 47), the number in complete remission (CR) and partial remission (PR) was 3 and 24, which shifted to 12 and 17 by month 6 (n = 41). Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six (P < 0.05 in all variables compared with responders). There was a significant reversible serum creatinine increase within 25% during month 3 to 12 (P < 0.05 in all variables compared with baseline value). Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of (1.04 ± 1.06) mg×kg(-1)×d(-1). Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment (> 30% rise of serum creatinine), secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively. CONCLUSIONS: The observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.