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Side effects of topical antiglaucoma drugs on the ocular surface: evaluation and challenge

Fudan University Journal of Medical Sciences.2012;39(1):86-93. doi:10.3969/j.issn.1672-8467.2012.01.017

Antiglaucoma medications are the first line therapy for the patients with primary open-angle glaucoma (POAG).As these intraocular pressure (IOP)-lowering agents are used for spanning years,good tolerability and better compliance are desired.Long-term application of antiglaucoma medications may exert side effects on ocular surface,which includes tear film,conjunctiva and cornea.These side effects can be attributable to the preservatives contained in the eye drops,e.g.,benzalkonium chloride (BAK).Preservative-free eye drops,vitamin A palmitate,antimetabolites,and new drug deliveries such as nanoemulsions and cationic emulsions,can contribute to minimizing the side effects as well as promoting the compliance and continuation of medication therapy.

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Systemic and cellular responses to intermittent hypoxia relevance to recurrent apnea syndrome

R.prabhakar NANDURI

Fudan University Journal of Medical Sciences.2012;39(1):1-4. doi:10.3969/j.issn.1672-8467.2012.01.001

Patients with sleep-disordered breathing with recurrent apneas exhibit autonomic dysfunction including elevated sympathetic nerve activity (SNA) and hypertension.Studies on experimental animals show that chronic intermittent hypoxia (CIH) resulting from recurrent apneas is a major stimulus for evoking autonomic dysfunction.In rodent models,CIH enhances arterial chemoreflex function in part due to enhanced carotid body sensitivity to hypoxia.The enhanced chemo-reflex leads to elevated sympathetic nerve activity.Recent studies suggest that transcriptional changes involving hypoxiainducible factor-1 and 2 (HIF-1,HIF-2) and the resulting reactive oxygen species-mediated signaling are critical cellular mechanisms underlying the chemoreflex-mediated excitation of sympathetic nervous system by CIH.

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The vagus nerve and pulmonary disease

Nana SONG ; Jun LIU ; Moldoveanu BOGDAN ; Guardiola JUAN ; Perez RAFAEL ; Jun YU

Fudan University Journal of Medical Sciences.2012;39(2):117-122. doi:10.3969/j.issn.1672 8467.2012.02.002

The vagus nerve innervates most visceral organs.Upon activation,vagal efferents release acetylcholine,which influences organ function.In addition,vagal afferents convey information regarding the mechanical and chemical environment of the organ to the central nervous system (CNS).This bidirectional communication provides a mechanism for reflex regulation of the biological function of the organ.In the lung,the vagus nerve modulates airway tone,perfusion and secretion,in addition to its effects on breathing pattern.Recently,the vagus nerve has been recognized to play a role in the pathogenesis of lung disease via neuro-immune interactions.The vagus nerve has significant influences in pulmonary diseases,such as asthma,chronic obstructive pulmonary disease (COPD),acute respiratory distress syndrome (ARDS),pulmonary fibrosis and lung cancer.In disease,the nerve is activated by cytokines,chemokines,and other mediators from many cell types to convey immunologic information to the CNS,which may alter disease outcome.Activation of the vagus nerve also releases neuropeptides to modulate immune cell behavior and can evoke the cholinergic anti-inflammatory pathway that regulates lung inflammation.Understanding the role of the vagus nerve in neuro-immune interaction may contribute significantly to the clinical management of pulmonary diseases.

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Recovery of respiratory motor function after spinal cord injury (SCI)

C.sieck GARY ; B.mantilla CARLOS

Fudan University Journal of Medical Sciences.2012;39(2):111-116. doi:10.3969/j.issn.1672-8467.2012.02.001

Upper cervical spinal cord injury SCI often results in diaphragm muscle (DIAm) paralysis.Clearly,it is important to understand how rhythmic phrenic activity can be restored in SCI patients.It is well establishedthatexcitatorypremotordrivetophrenicmotorneurons(PhMn)emanates predominantly from the ipsilateral medulla.As a result,after C2 spinal cord hemisection (SH) ipsilateral excitatory input is removed and rhythmic phrenic activity disappears on the affected side.However,a latent contralateral excitatory input to PhMn exists that can be strengthened with time (neuroplasticity) leading to functional recovery of rhythmic phrenic activity.Converging evidence suggests that neurotrophins (e.g.,brain-derived neurotrophic factor,BDNF) acting through tropomyosin related kinase receptors (e.g.,TrkB) play an important role in neuroplasticity.Our results indicate that intrathecal BDNF treatment enhances functional recovery of rhythmic phrenic activity,whereas intrathecal treatment with TrkB-Fc,a fusion protein that quenches extracellular BDNF delays functional recovery.Targeted enhancement of TrkB expression in PhMn using adeno-associated viral vectors (AAV) also enhances functional recovery,whereas siRNA-induced knockdown of TrkB in PhMn delays recovery.Together,these results indicate that enhancement of BDNF-TrkB signaling in PhMn may be effective therapy to promote functional recovery after upper cervical SCI.

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The influence of age on retinal nerve fiber layer thickness in adults

Xiaoyun MA ; Gezhi XU

Fudan University Journal of Medical Sciences.2009;36(2):216-220.

Objective To evaluate the association of age and retinal nerve fiber layer (RNFL) thickness by means of scanning laser polarimetry in a sample of healthy Chinese eyes. Methods One hundred and fifty eyes of 150 healthy subjects underwent RNFL scan in two different modes (Variable Cornea Compensation,VCC;Enhanced Cornea Compensation,ECC) of Glaucoma Diagnosis Variable Cornea Compensation Nerve Fiber Analyzer.The parameters included temporal-superior-nasal-inferior-temporal (TSNIT) average,superior average,inferior average,TSNIT standard deviation,and nerve fiber indicator (NFI). Results Mean values of TSNIT average,superior average,inferior average,TSNIT standard deviation and NFI in VCC mode were (57.12±6.26),(69.35±4.21),(67.59±7.06),(25.46±4.02),(17.35±7.59),while the parameters' values in ECC mode were (56.15±5.32),(68.24±6.63),(66.90±2.40),(24.80±6.76),(18.84±8.51),respectively.The differences between the values of VCC and ECC modes were not statistically significant.The parameters' values of total subjects were associated with age.But there were no significant associations between age and parameter values in the eyes of those older than 40 years old subjects. Conclusions There are no significant differences between the RNFL values detected by VCC and ECC modes in 150 healthy Chinese eyes.Age has influence on RNFL thinning in 21-70 years old healthy eyes,but not in the eyes of older than 40 years old people.

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Effects of hawthorn leaf flavonoids on reducing blood lipids and preventing fatty liver in the quails

Xiyun YE ; Minhua XU ; Xiaofeng LI ; Yaofa WANG

Fudan University Journal of Medical Sciences.2009;36(2):142-148.

Objective To investigate the effect of hawthorn leaf flavonoids (HLFs) with the different concentrations in prevention of high blood lipids and fatty liver in quails. Methods Sixty quails were divided into six groups:normal (N),high lipids food model (M),positive control (ZBT),HLF1,HLF2 and HLF3 groups.The animals in the N group were fed with normal food,while the M group was feed with high lipids food to establish the animal model of fatty liver.Besides high-fat diet,HLF1,HLF2 and HLF3 groups were also fed with 1 mL HLFs in the doses of 20 mg/kg,40 mg/kg and 80 mg/kg respectively.The ZBT group was fed with 1 g/kg of ZhiBiTuo and used as the positive control.After the experiments of six months,the serum and liver of the quails were taken and used to evaluate the contents of total cholesterol (TC),triglyceride (TG),high density lipid cholesterol(HDL-C),low density lipid cholesterol (LDL-C),superoxide dismutase (SOD),malondialdehyde (MDA),glutathione (GSH),alanine amino transferase (ALT) and glutamic oxaloacetic transaminase (AST).Meanwhile,the microscopic and electronic microscopic sections were used to observe the pathological changes of the livers of the quails. Results Compared with the M group,HLFs significantly lowered the content of TC,TG,LDL-C,MDA,AST and ALT in the serum and livers of the quails in other groups (P<0.001).However,the levels of HDL-C,SOD and GSH of the other groups were increased markedly (P<0.001).Moreover,the ratios of increase/decrease in the three HLF groups were depended on the concentrations of HLFs.Also,better liver structure and less lipid accumulation were also observed in the HLF groups when compared to the M group. Conclusions These results showed HLFs can lower blood lipid and cholesterol accumulation,improve the antioxidant capacity and protect the physiological function of liver.So,HLFs were effective in preventing and treating high blood lipids and fatty liver induced by high-fat diet.

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A sensitive HPLC method for determination of amphotericin B and itraconazole in cerebrospinal fluid and its application to patients with cryptococcal meningitis

Zheng JIANG ; Liping ZHU ; Cunjing YU ; Yunqiu YU

Fudan University Journal of Medical Sciences.2008;35(6):866-872.

Objective To establish a sensitive, rapid and simple high-performance liquid chromatography (HPLC) method for the determination of amphotericin B (AraB) and itraconazole (ITZ) in human cerebrospinal fluid (CSF). Methods Solid-phase extraction (SPE) was involved in sample preparation in this method, followed by reverse-phase separation under two different chromatographic systems. Results The tinearity for both AraB and ITZ ranged from 5 ng/mL to 100 ng/mL and the inter-day and intra-day RSD were both below 7.6% at the concentrations of 20,50 and 100 ng/mL. Conclusions The method we established has been applied to the therapeutic drug monitoring on cryptococcal-meningitis-infected patients who were given comedication of these two drugs.

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Treatment of port wine stains with photodynamie therapy in Chinese patients

Mengying LIN ; Leihong XIANG

Fudan University Journal of Medical Sciences.2008;35(2):300-303.

Port wine stains affect patients on either cosmetic or functional, and even psychological aspects. Although many therapeutic modalities have been applied, the effective clearance rate of this bothersome problem is still limited to some extent. Photodynamic therapy is a state-of -the-art option for patients with port wine stains. In this article, clearance rates and adverse effects of different photo-dynamic therapy measures (including photosensitizers and light sources) for Chinese patients were re-viewed.

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Expression of small glutamine-rich TPR-containing protein in the developing mouse brain

Ling SONG ; Yuanyuan RUAN ; Yanlin WANG ; Xiaojing YUN ; Ying ZHANG

Fudan University Journal of Medical Sciences.2007;34(6):793-799.

Purpose The aim of this study was to reveal the role of SGT,the small glutamine-rich tetratricopeptide repeat (TPR)-containing protein,in the developing mouse brain through examining the expression profile of SGT during the development stage. Methods In this study, quantitative RT-RCR and Western blot were applied to investigate the expression of SGT mRNA and protein in the mouse whole brain. Western bolt was also used to detect the expression of SGT in the hippocampus, cerebral cortex, striatum and cerebellum. Immunohistochemical analysis on postnatal and adult mouse brain was performed to examine the subcellular localization of SGT. Results Our data showed that the levels of SGT mRNA and protein in the mouse whole brain were both high during the postnatal stage and declined in the adult. Regional expression of SGT protein in the hippocampus, cerebral cortex, striatum and cerebellum showed a similar expression profile.Immunohistochemical analysis found that in the P14 mouse brain, SGT was abundant in all the CA regions of hippocampus as well as most regions of cerebral cortex and striatum. In the cerebellum, SGT was mainly distributed in Purkinje cells. In the sections of the adult mouse brain, faint expression was observed in the regions mentioned above. Conclusions Our findings firstly exhibit the expression pattern of SGT in the mouse brain development,which might shed new light on further functional analysis of SGT in the central nervous system.

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Bioavailability and pharmacokinetics of two sustained release formulations of mizolastine in healthy volunteers

Zhiwen ZHANG ; Lijun ZHANG ; Jiang WU ; Xianyi SHA ; Xiaoling FANG

Fudan University Journal of Medical Sciences.2007;34(2):216-222.

Purpose The aim of this study was to compare the pharmacokinetic(PK) profile and relative bioavailability of two sustained release tablets containing 10 mg mizolastine in healthy, young Chinese volunteers. Methods A single oral dose of mizolastine was given under fasting conditions to volunteers aged from 21 to 24 years in this open-label, randomized, crossover study. A ten-day washout period was applied between each of the two formulations. Plasma samples were obtained before dosing and at predetermined time points after dosing up to 48 hours and were analyzed for plasma concentration with a high-performance-liquid chromatography-UV method. PK parameters representing the extent and the rate of absorption of mizolastine were obtained. An analysis of variance, 90% confidence intervals, and two one-sided tests were employed for statistical analysis of relative difference between the two formulations. Results According to the pharmacokinetic and statistical analysis, parameters were not statistically different between the two formulations except the peak concentration (cmax). The point estimates of the ratios of AUC0→t, AUC0→∞ of mizolastine were (101.26 + 9.82) % and (102.52 + 8.61)% with 90% confidence intervals (CIs) of 95. 5% - 106. 5% and 97. 7% -106.9% respectively, comprised in the stipulated 80% - 125% range; for cmax values, the ratios was 82.17% - 15.32% with the 90% CIs of 71. 7% - 91.1%, fell in the recommended range of 70% -143%. Conclusions The results indicate that there is no statistically significant difference in PK parameters except cmax between the two sustained release tablets of mizolastine. The 90% CIs of AUC0→t,AUC0→∞ and cmax are within the predefined range. Thus, the two sustained release tablets of mizolastine are considered bioequivalent and generally well tolerated.

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