Interaction of secreted phospholipase A2 and Pulmonary surfactant and its pathophysiological relevance in acute respiratory distress svndrome

Phospholipases A_2(PLA_2s)belong to a family of enzymes that hydrolyze phospholipids at the sn-2 position leading to the liberation of fatty acids and lysophospholipids(Fig 1). Mammaliall PLA_2s are divided into two major classes according to their location: high molecular mass intracellular PLA_2 and low molecular mass secreted PLA_2(sPLA_2)(Fig 2). There have been Substantial progresses in understanding the regulation of sPLA_2 expression. especiallv the type-ⅡA sPLA_2     

Ubiquitin–proteasome system-targeted therapy for uveal melanoma: what is the evidence?

Uveal melanoma(UM)is a rare ocular tumor.The loss of BRCA1-associated protein 1(BAP1)and the aberrant activation of G protein subunit alpha q(GNAQ)/G protein subunit alpha 11(GNA11)contribute to the frequent metastasis of UM.Thus far,limited molecular-targeted therapies have been developed for the clinical treatment of UM.However,an increasing number of studies have revealed the close relationship between the ubiquitin proteasome system(UPS)and the malignancy of UM.UPS consists of a three-enzyme cascade,i.e.ubiquitin-activating enzymes(E1s);ubiquitin-conjugating enzymes(E2s);and ubiquitin-protein ligases(E3s),as well as 26S proteasome and deubiquitinases(DUBs),which work coordinately to dictate the fate of intracellular proteins through regulating ubiquitination,thus influencing cell viability.Due to the critical role of UPS in tumors,we here provide an overview of the crosstalk between UPS and the malignancy of UM,discuss the current UPS-targeted therapies in UM and highlight its potential in developing novel regimens for UM.     

Preparation of PLA or PLGA Microspheres with Estradiol the Effects of THF—adding on the Properties of MS

Aim: polylactic acid(PLA) or polylactide-co-glycolide(PLGA) was used as biodegradable and biocompatible carriers to achieve sustained release of estradial-PLGA/PLA-Microspheres(E2-PLGA/PLA-MS).THF was added in the organic phase to study its effects on the properties of MS.Methods:MS were formed by an emulsification-solvent extraction method with mixture of ethyl acetate(EtoAc) and tetraphydrofuran(THF) as the organic solvents,and then the properties and in vitro drug release behavior were examined.Results:The results indicated that the drug loading efficiency decreased when THF added.but when the ratio of EtoAc was more than 50%,there was no obvious effcet of THF ration,but the particle size increased accordingly.The carriers‘ properties and the drug contents were the main factors influencing the in vitro drug release.Conclusions:By controlling the technology and formulation,we can get sustained-release E2 biodegradable microsperes with proper particle size,drug content and low burst-release,although THF with readily solubility in water was used in the organic phase.     

Gene cloning, expression, purification and characterization of lipoprotein- associated phospholipase A2 in Pichia pastoris

AIM To express and purify Lipoprotein -associated phospholipase A2 (Lp-PLA2), and to establish a screening model for Lp-PLA2 inhibitors through the recombinant Lp-PLA2. METHODS The full-length gene of Lp-PLA2 was cloned from the differentiated THP-1 cells by RT-PCR and PCR. The Lp-PLA2 gene was subcloned into the Pichia expression vector pPIC9 and introduced a sequence encoding a C-terminal stretch of six histidine residues at the same time. The recombinant plasmid was transformed into Pichia pastoris GS115 by spheroplasting and the gene was then integrated into the GS115 genome. Lp- PLA2 was expressed in the yeast strain GS115 by inducing with 0.5% methanol.     

经尿道前列腺电汽化术

Forty-four cases of benign prostate hyperplasia were underwent using transurethral electrovaporization of prostate (TUVP). The average age of the patients was 71.3,and the mean operation time was 55min. The mean indwelling catheter time was 54h, capable of voiding fredy after the removal of the catheter. International prostate symptom score(I-PSS) dropped from 28.9 before the procedure to 7.2 postoperatively. Q_max increased from 4.9ml/s to 18.3ml/s. Neither transurethral resection syndrome nor severe bleeding occurred in the patients. TUVP was daimed to be effective and safe with less bleeding and few complications and less trauma to the patients     

Leflunomide increased the renal exposure of acyclovir by inhibiting OAT1/3 and MRP2

Rheumatoid arthritis patients can be prescribed a combination of immunosuppressive drug leflunomide(LEF)and the antiviral drug acyclovir to reduce the high risk of infection.Acyclovir is a substrate of organic anion transporter(OAT)1/3 and multidrug resistance-associated protein(MRP)2.Considering the extraordinarily long half-life of LEF’s active metabolite teriflunomide(TER)and the kidney injury risk of acyclovir,it is necessary to elucidate the potential impact of LEF on the disposition of acyclovir.Here we used a specific MRP inhibitor MK571 and probenecid(OAT1/3 and MRP2 inhibitor)to assess the effects of MRP2 and OAT1/3 on the pharmacokinetics and tissue distribution of acyclovir in rats.We showed that LEF and probenecid,but not MK571 significantly increased the plasma concentration of acyclovir.However,kidney and liver exposures of acyclovir were increased when coadministered with LEF,probenecid or MK571.The kidney/plasma ratio of acyclovir was increased to approximately 2-fold by LEF or probenecid,whereas it was increased to as much as 14.5-fold by MK571.Consistently,these drugs markedly decreased the urinary excretion of acyclovir.TER(0.5−100μmol/L)dose-dependently increased the accumulation of acyclovir in MRP2-MDCK cells with an IC50 value of 4.91μmol/L.TER(5μmol/L)significantly inhibited the uptake of acyclovir in hOAT1/3-HEK293 cells.These results suggest that LEF/TER increased the kidney accumulation of acyclovir by inhibiting the efflux transporter MRP2,which increased its kidney/plasma ratio and renal injury risk.However,the inhibitory effects of LEF/TER on OAT1/3 reduced the tubular cells’uptake of acyclovir and increased the plasma concentration.     

Drug development and immunotoxicity

Immunotoxicity of drugs has to be evaluated same as other kinds of toxicities,since the functions of the immune system are vital to human survival,consisting of the protection of the body from invading pathogens and to provide immune surveillance against arising tumor cells.A given drug‘s effect on the immune system can be classified as (1)immuno-suppression/activation.(2)antigenicity and hypersensitivity,(3)autoimmunity.The guidance of immumotoxicity has highlighted on immuno-suppression in Harmonizing Congress among EC,USA and Japan.In this paper,the strategy and methods to evaluate immunotoxicity,mainly immuno-suppression,of the drugs will be show.complexity and variety of immuno-systems make assessment of immumotoxicity complex.The testing in rats to assess immune function is thought to be the first choice for immunotoxicity evaluation in a drug development,and then other suitable testing should be added depending on the mature of drugs.     

Increased expression of α-synuclein in different age APP transgenic mice model of Alzheimer＇ s disease and intervention by Chinese components

AIM To investigate the expression change of α-synuclein in the brain of different age AD-like an-imal model and to explore the pathology mechanism of α-synuclein in neural degeneration and protective effect of 2 kinds of Chinese components. METHODS A generally accepted animal model of Alzheimer‘ s disease-APP V717I transgenic (Tg) mouse was observed from 4 to 16 month old. The Tg mice wererandomly divided into model group(4 month, 10 month and 16 month old), Shen-wu capsule with the dose of 0.4g and 1.2g/kg/d, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside(TSG), one of effective components in Polygonum muhiflorum, at dose of 0. 05,0.1 and 0.2g/kg/d.     

陇东蛇丹墨的制作方法

Objective To make good use of ophidian medicinal materials, preserve and develop Chinese folk medicine. Method Through sufficient investigation, it‘s known that the making of Shedanmo (a kind of Chinese folk medicine in east of Gansu province ,made from fermented snake) can be divided into three steps:catching,compounding,and fermenting.Result The qualified Shedanmo,which is fermented well,should be black and brown ropy liquid full of fishniness. Conclusion According to folk recipe, Shedanmo is widely used to treat inflamed wound effectively.It‘s of dual significance to explore the rare folk treasure in enriching the species of Chinese traditional medicine and the full use of ophidiam medieinal materials.     

Ca^2＋ sparks evoked by depolarization of rat ventricular myocytes involve multiple release sites

AIM:To investigate the fundamental nature of calcium release events (Ca^2 ‘sparks’) evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling. METHODS: High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca^2 sparks and sparks evoked by depolarization. RESULTS: 1)Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35mV appeared to arise at single sites spacing about 1.80μm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at halfmaximal amplitude:FWHM) followed single Gaussian distributions with means of 2.6μm. 2)Different to this,transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9μm for spontaneous sparks and ith means of 1.9 and 3.1 μm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca^2 sparks evoked by depolarization are not ′unitary′ events, but often involve multiple sites of origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca^2 released during sparks directly triggered by influx through L-type Ca^2 channels may, in turn, trigger neighboring sites. The restricted involvement of only a few transverse release sites preserves the essential feature of the ‘local control’ theory of E-C coupling.     

Degraded and undegraded carrageenans and experimental gastric and duodenal ulceration

The prevention of histamine-induced gastric and duodenal ulceration in the guinea-pig has been examined using a series of undegraded and degraded carrageenans. Undegraded carrageenans were active at lower doses than degraded carrageenans. The high viscosity of the undegraded carrageenans in solution prevented their use in larger doses. Degradation of carrageenan without serious loss of sulphate, gives a product which allows the dose to be increased to an extent that its effect more than offsets the slight loss in activity caused by the degradation. No single feature of carrageenan structure can be related to anti-ulcer activity although degradation, and hence reduction of molecular size, generally reduces activity. Sulphate contents over 30% have little apparent effect on activity; κ-carrageenans were not consistently different in anti-ulcer activity from Λ-carrageenans. This contrasts with the antipeptic activity of carrageenans where κ-carrageenans are less active than their Λ-counter-parts. As with antipeptic activity, the degree of anti-ulcer activity is probably determined by a combination of structural features which includes molecular size and polyanionic properties.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Alcohol and Substance Use and Abuse in Women and Children

No abstract available for this article.     

Glucosidase and fucosidase inhibitors and Advances in nucleosides and nucleotides.

The American Chemical Society Symposium "Glucosidase and fucosidase inhibitors" took place on 1 April 1998 and was organized by Professors Zbigniew J Witczak (UConn, School of Pharmacy, CT, USA), Kuniaki Tatsuta (Waseda University, Tokyo, Japan) and Waldemar Priebe, MD (Anderson Cancer Center, University of Texas, USA). Professor Witczak provided introductory remarks including the status of existing glucosidase inhibitors, and chaired the morning session, which consisted of six lectures. The symposium was well received, and was particularly attractive for those interested in networking, as attendance was about sixty. In addition, some participants and attendees presented posters on the subject during the regular poster session organized by the Division of Carbohydrate Chemistry.