OBJECTIVE:To discuss the characteristics and regularities of adverse drug reactions(ADR)occurring in our hospital.METHODS:A total of 1 451 ADR cases collected by ADR monitoring center in 2007 were analyzed statistically in respect of patients' age,routes of administration,drug category,ADR-involved organs or systems and clinical manifestations etc.RESULTS:Of the 1 451 ADR cases,72.16% of the ADR-inducing drugs were administered by intravenous drip,and most were associated with anti-infective drugs,predominantly penicillins,cephalosporins and quinolones.The ADR manifested predominantly as lesions of skin and its appendants.CONCLUSION:Rational drug use and ADR monitoring should be strengthened to reduce or avoid the occurrence of ADR.

Objective To evaluate the effects of Prinsepia utilis Royle oil (PURO) on the synthesis of ceramide and expression of acid ceramidase N-acylsphingosine amidohydrolase 1 (ASH1),and to explore the mechanisms underlying its moisturizing and skin barrier-repairing effects.Methods Keratinocytes from human foreskin tissue were classified into 2 groups to be cultured in keratinocyte-serum free medium (K-SFM) with or without the presence of PURO.Enzyme linked immunosorbent assay (ELISA) was performed to measure the level of ceramide in the culture supernatant of keratinocytes at 0,3,8,24 and 48 hours.The back of nude mice was divided into 4 areas,i.e.,test area,matrix area,blank control area and negative control area.Acetone and ether were used to destroy the epidermal barrier in the test,matrix,and blank control areas,then,the former 2 areas were topically treated with emulsions containing 1％ PURO and matrix,respectively,and the blank control area remained untreated.The epidermal barrier remained intact and untreated in the negative control area.Noninvasive methods were used to determine transepidermal water loss (TEWL),epidermal moisture content and skin lipid content in these areas on day 0,1,3,and 7.Skin tissue was obtained from these areas on day 0 and 7 followed by an immunohistochemical study for the quantification of ASH1 expression.Results The level of supernatant ceramide increased with time in the PURO-treated keratinocytes,which was significantly higher at 24 hours and 48 hours than at 0 hour (1.3817 ± 0.100 and 1.3737 ± 0.047 vs.0.7630 ± 0.143,both P ＜ 0.05).The supernatant ceramide was also elevated in the PURO-treated keratinocytes compared with untreated keratinocytes at 24 and 48 hours (both P ＜ 0.05).Noninvasive skin tests showed a gradual decrease in the TEWL,but an increase in the epidermal moisture content and skin lipid content with time in the 3 epidermal barrier-destroyed areas.As far as the test area was concerned,TEWL value was significantly lower on day 3 and 7 than on day 0 (10.85 ± 0.64 and 8.01 ± 0.58 vs.12.65 ± 0.71,both P ＜ 0.05),while a significant increment was observed in the skin lipid content on day 3 and 7 compared with day 0 (29.14 ± 0.40 and 31.30 ± 0.88 vs.27.02 ± 0.65,both P ＜ 0.05),as well as in the epidermal moisture content on day 1,3 and 7 compared with day 0 (13.98 ± 0.28,15.00 ± 0.38 and 15.86 ± 0.18 vs.11.74 ± 0.62,all P＜ 0.05).On day 7,there was a statistical decline in TEWL value,but an elevation in epidermal moisture content,skin lipid content and ASH1 expression in the test area compared with the matrix area and blank control area (all P ＜ 0.05).Also,the expression of ASH1 was upregulated on day 7 compared with day 0 in the 3 barrier-destroyed areas (all P ＜ 0.05).Conclusion PURO may exert skin-moisturizing and barrier-repairing effects by enhancing the synthesis of ceramide and expression of acid ceramidase ASH1.

Objective To evaluate the differences of clinical features,neuroimaging,angiography and laboratory findings between different stroke subtypes according to TOAST criteria in elderly patients.Methods 91 patients (aged ≥ 80 years) with acute ischemic stroke were retrospectively reviewed in Departement of Neurology from April 2009 to August 2010.Subtypes of ischemic stroke were analyzed according to the classification of TOAST.Risk factors,clinical manifestations,complications,prognosis,neuroimaging,cerebrovascular lesions,and laboratory findings of different TOAST subtypes were compared.Results Large-artery atherosclerosis (LAA) (34/91) was the most common cause of acute ischemic stroke in elderly patients,and most criminal lesions (25/34) located at the intracranial arteries.In the LAA group,patients with intracranial (25/34) or extracranial (12/34) occlusive diseases were more than those in other groups.Patients with cardioembolism (CE) had lower lipid levels.In the CE group,patients with poor shortterm prognosis (7/15) were more than in the LAA or small-artery occlusion (SAO) group,and patients with severe cerebral edema (4/15) were more than those in other groups.In patients of the SAO group,complications occurred infrequently (4/20),and none had poor short-term prognosis.Conclusions There were some differences among different TOAST subtypes in clinical features,neuroimaging,cerebrovascular diseases,and laboratory findings.The clinical significance of our findings needs to be explored further.

Objective To investigate the correlation of epidermal distribution of lamellar bodies and expression of ceramidase with skin barrier dysfunction in polymorphous light eruption.Methods Forty-seven patients with polymorphous light eruption and 40 healthy volunteers were recruited into this study.Noninvasive instruments were used to measure skin sebum content,transepidermal water loss(TEWL)and water content in stratum corneum in all of the subjects.Then,tissue specimens were obtained from the lesions at sunexposed sites in the patients and normal skin of the healthy volunteers.The ultrastructure and distribution of lamellar bodies were observed with transmission electron microscopy in five lesion and control specimens.Immunohistochemistry was performed to detect the expression of ceramidase in the tissue specimens.Results Compared with the normal skin from healthy volunteers,the lesions from patients showed decreased number of lamellar bodies in the granular layer and prick cell layer with a disorganized arrangement.Ceramidase was positively expressed in 20 lesion specimens and 36 normal control specimens,weakly expressed in 21 lesion specimens and 4 normal control specimens,and negative in 6 lesion specimens; there was a significant difference in the expression of ceramidase between the lesion specimens and normal control specimens(P ＜ 0.01).The lesions also showed high TEWL(34.2191 ± 12.70 vs.16.8350 ± 6.50,P ＜ 0.01),lower water content in stratum corneum(22.7319 ± 8.71 vs.29.4250 ± 5.08,P ＜ 0.01)and similar skin sebum content compared with the normal skin.Conclusions There is a disturbance in the synthesis of ceramide in patients with polymorphous light eruption,which may contribute to the impairment of skin barrier.

Reuse of waste oil in cooking has been the social concern for long time, but until now there is no reliable method to identify the gutter oil.In this work, based on the generation of long-chain aliphatic aldehydes in the refinement of gutter oil, gutter oil and adulterate cooking oil were identified by determining hexanal, heptanal, octanal, nonanal and decanal in oil sample with high perfomance liquid chromatography (HPLC) method using O-(3-(9H-carbazol-9-yl)propyl)hydroxylamine as the fluorescent derivative reagent.At first, 10 μL of oil sample was dissolved in 200 μL of isopropanol, then reacted with O-(3-(9H-carbazol-9-yl)propyl)hydroxylamine to form the stable derivatives, extracted with acetonitrile and injected into HPLC for analysis.The derivatives were separated on a C18 column within 15 min with ACN-H2O (90∶10, V/V) as mobile phase.The fluorescence detector was set at λex/λem=292 nm/348 nm.The linear range of 5 kinds of long-chain aliphatic aldehydes was 0.01-1.00 μmol/L with limit of detection (LOD, S/N=3) of 0.05-0.10 nmol/L, and the spiked recoveries were 95.6%-101.4%.The results showed that the edible oils obtained from supermarket almost had no hexanal, heptanal, octanal, nonanal, decanal, but these aldehydes increased significantly in gutter oil.Thus the 5 kinds of long-chain aldehydes could be used as the indictor of gutter oil.Taking the advantage of good specificity, higher sensitivity, good accuracy and simplicity, the method was suitable for the rapid identification of gutter oil.

ObjectiveTo seek experimental evidence of epidermal barrier dysfunction in psoriasis,and to provide a basis for adjuvant therapy of psoriasis.MethodsPhysiometric methods were used to determine the value of sebum content,transepidermal water loss(TEWL) and water content of stratum corneum in 60 patients with psoriasis and 48 normal human controls.The ultrastructure of lamellar bodies was observed with transmission electron microscopy,and the expression of acid ceramidase in normal skin and psoriatic lesions was detected by using immunohistochemical techniques.ResultsCompared with the normal skin,TEWL value was increased(P ＜ 0.01),but water content of stratum corneum decreased(P ＜ 0.01 ) in psoriatic lesions,and sebum content was similar between normal skin and psoriatic lesions.As electron microscopy showed,lamellar bodies in keratinocytes were reduced in number with a disorganized arrangement and irregular size in psoriatic lesions.The expression of acid ceramidase also decreased in psoriatic epidermis.Conclusions The function of epidermal barrier in psoriasis is impaired,and to restore epidermal barrier function and enhance hydration may serve as an important adjuvant therapy of psoriasis.

Background Trans-corneally subretinal injection in rodent model is a useful method for genetic therapy,stem cell transplantation and the study on the ophthalmic research.Standarized operation process is critical for the successful treatment.However,there is no literature to report the detailed procedure and the influence of this technique on morphology and function of retina.Objective This sudy was to introduce a method of trans-corneally subretinal injection and evaluate its influence on the morphology and function of retina.Methods Trans-corneallly subretinal injection was performed on the left eyes of 2-month-old SPF C57BL/6J mice after dilation of pupils.A 301/2G disposable needle was used to puncture the cornea within the pupil area near limbus and avoid touching the lens and irises under eye surgery microscope.Then,a 33G blunt needle was used to insert into the vitreous and toward subretinal space via corneal puncture.Normal saline with 0.1％ fluorescein sodium of 1 μl was slowly injected into the space,and 2.5％ hydroxypropyl methylcellulose was dropped on ocular surface for the observation of the fundus clearly.According to the percentage of the retina filled with subretinally injected solution,the experimental eyes were divided into 80％-100％ area group,50％-70％ area group after injection,and the mice in the pseudo-injected group,in which injection procedure stopped just before the solution was pushed in to the subretinal space did not inject any solution after punctured.The right uninjected eyes of the mice served as normal control group.Four eyes were selected for each group.The structural changes were evaluated by optical coherance tomograpby (OCT) 1 day,2 days,3 days and 5 weeks after injection,and retinal function was assessed by the recored of electroretinography (ERG) 5 weeks after injection.The retinal sepcimens were prepared to examin the morphological changes by hematoxylin and esosin staning.The use of care followd the Regulations for the Administration of Affair Concerning Experimental Animals of Zhejiang Province.Results About 70％ of the injected eyes showed that retinal blebs filled with injected green fluorescein solution occupied 50％ or more retinal area with minimal damages.The focal detachment between neurosensory retinal layer and retinal pigment epithelium (RPE) was exhibited 1 day postinjection,and almost all the retinas retached 2 days after injection.In the fifth week after injection,the amplitudes of ERG b wave were (386.25±37.88),(357.50±41.03),(324.25±53.45) and (410.50±14.88) μV in the sham operation group,50％-70％ area group,80％-100％ area group and normal control group,respectively,showing a significant difference among the 4 groups (F=3.574,P=0.047),and the amplitudes of b wave in the normal control group were higher than those in the 80％-100％ area group (all at P ＜ 0.05).The detachment between retinal neuroepithelium layer and RPE layer,cell proliferation and transposition in the outer nuclear layer were dispalyed under the light microscope in the sham operation group,50％-70％ area group and 80％-100％ area group,and the disordered outer segment of photoreceptors at the injecting area was seen in the 50％-70％ area and 80％-100％ area groups at five weeks after injection.However,retinal sructure and morphology were normal at the non-injection area.Conclusions Trans-corneally subretinal injection is an effective and safe way for subretinal injection.

Stargardt disease (STGD) is an inherited disorder of retinal pigment epithelium.Three genes have been found to be implicated in STGD including Abca4 (adenosine triphosphate-binding cassette,sub-family A,member 4),Elovl4 (elongation of very long chain fatty acids protein 4) and Prom1 (prominin-1).Target genes can be delivered to the retina by various methods such as lentivirus (LV) vectors,adeno-associated virus (AAV) vectors and non-viral nano-particles.The Abca4-/-,Elovl4-/-and Prom1-/ mice model are used to study the pathogenesis mechanism and treatment of STGD.Retinal function improved significantly upon gene therapy in these models.Based on these works using animal model,phase Ⅰ /Ⅱ a clinical trial of Abca4-associated STGD gene therapy are underway.As a LV vector,equine infectious anemia virus (EIAV) is used to carry the Abca4 gene.These studies will evaluate three dose levels of the EIAV vector for safety,tolerability and biological activity.Moreover,some preclinical attempts to deliver Abca4 via AAV have been made using a modified AAV vectors because of the large size of the ABCA4 cDNA.The good responses in animal models render STGD a very attractive object for human gene therapy after the successful of the phase Ⅰ /Ⅱ clinical trials of Leber's congenital amaurosis.

Objective To investigate the relationship of Toll-like receptors (TLRs) 2 and 4 with the occurrence of chloasma.Methods Peripheral blood samples were collected from 40 patients with chloasma and 40 healthy human controls,and skin samples were also collected from the lesions of 10 of the patients and normal skin of 10 of the healthy controls.Real time (RT)-PCR was performed to measure the mRNA expressions of TLR2 and TLR4 in skin lesions and blood samples.An immunohistochemical test was conducted to observe the expressions of TLR2 and TLR4 in skin lesions.Statistical analysis was carried out by t test.Results The expressions of TLR2 and TLR4 mRNAs were both significantly higher in skin lesions of the patients than in normal skin of the controls (9.72 ± 2.93 vs.5.10 ± 2.69,t =3.67,P＜ 0.01; 9.52 ± 2.88 vs.4.77 ± 1.90,t =4.36,P＜ 0.01),while no significant difference was found in the mRNA expressions of TLR2 or TLR4 in peripheral blood between the patients and controls (both P ＞ 0.05).As the immunohistochemical test revealed,TLR2 was absent in both the epidermis and vascular endothelial cells in 6 normal control skin samples,weakly expressed in the basal layer of the epidermis but absent in vascular endothelial cells in 4 normal skin samples,and no TLR4 expression was observed in either the epidermis or vascular endothelial cells in these control skin samples.Among the 10 skin samples from chloasma lesions,3 showed TLR2 expression in the whole epidermis,7 in both basal cell layer and prickle cell layer but not in vascular endothelial cells in the superficial dermal layer,all showed strong TLR4 expression in the basal cell layer and weak TLR4 expression in the prickle cell layer,and 3 exhibited TLR4 expression in vascular endothelial cells in the superficial dermal layer.Conclusion TLR-mediated immune responses in local skin might be related to the occurrence of chloasma.

Animals ; Cells, Cultured ; Ethanol ; toxicity ; Hepatocytes ; drug effects ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Transcription Factor RelA ; metabolism