NSAID对胰腺癌中COX-2的表达及其生长活力的影响

目的 :检测胰腺癌中COX 2表达 ,探讨COX 2抑制剂非甾体类消炎药 (NSAID)的抑癌机制。方法 :胰腺癌组织和细胞株中的COX 2检测分别采用免疫组化和细胞免疫化学分析 ,并使用MTT法及流式细胞仪检测细胞株生长活力和凋亡。结果 :胰腺癌组织中COX 2的表达增强 ,阳性率 73.3% (P <0 .0 5 )。SW 1 990和Capan 2细胞株均有COX 2表达 ,前者高表达 ,后者低表达。两种NSAID(NS398及ASA)均可抑制两种细胞株的生长 ,诱导细胞凋亡率显著升高 ,并与细胞株COX 2表达强度有关 ;对SW 1 990细胞株的作用强于Capan 2 ,NS398的抑制作用又强于ASA。结论 :COX 2在胰腺癌组织和细胞株中表达增强 ,NSAID抗胰腺癌机制可能是通过抑制COX 2活性 ,诱导胰腺癌细胞凋亡     

In vivo activity of cefodizime

Cefodizime has been shown to possess highin vivo antibacterial activity in a variety of experimental infection models involving different body systems and animal species: systemic infections, pneumonia and urinary tract infections in normal mice, intrauterine infections in normal rats, and meningitis in normal rabbits, as well as systemic infections in immunosuppressed animals. Most investigations found that the therapeutic efficacy of cefodizime frequently exceeded the one expected from itsin vitro values and in many cases compared favorably with those of other cephems, even when thein vitro susceptibility of the infecting organism to these drugs was markedly higher. These findings have been attributed either to the superior kinetic profile of cefodizime — prolonged serum half-life and excellent tissue penetration with long-lasting levels — or to a synergy between its high bactericidal activity and host defence mechanisms. The parallel consideration of the MIC₉₀ values of cefodizime and the pharmacokinetic profile of this agent in humans indicate that the vast majority of the relevant respiratory and urinary pathogens are covered by once-a-day cefodizime dosage regimens of either 1 or 2 g.Cefodizim erwies sich in einer Reihe von experimentellenin vivo Infektionsmodellen, die an verschiedenen Organsystemen und Versuchstierspezies durchgeführt wurden, als überaus wirksam: systemische Infektionen, Pneumonie und Harnwegsinfekte (normale Mäuse), intrauterine Infektionen (normale Ratten), Meningitis (normale Kaninchen), aber auch systemische Infektionen bei immunsupprimierten Versuchstieren. Zumeist attestierten die Untersucher Cefodizim eine therapeutische Wirksamkeit, die diejenige übertraf, die aufgrund derin vitro Daten zu erwarten war. Häufig erwies sich Cefodizim als wirksamer als die eingesetzten Referenz-Cepheme, gegenüber denen die untersuchten Keimein vitro in manchen Fällen eine deutlich günstigere Empfindlichkeit aufwiesen. Diese Befunde wurden entweder auf das überlegene pharmakokinetische Profil von Cefodizim — verlängerte Eliminationshalbwertszeit und ausgezeichnete Gewebsgängigkeit — zurückgeführt, oder aber auf einen Synergismus zwischen der hohen antibakteriellen Aktivität und einer gesteigerten Abwehrlage. Bei Betrachtung der MHK₉₀-Werte und des pharmakokinetischen Profils von Cefodizim kann geschlossen werden, daß die überwiegende Mehrzahl der bei Infektionen des Respirations- und Harntraktes relevanten Erreger mit einer einmal täglichen Gabe von 1 oder 2 g erfaßt wird.     

In vivo evaluation of antiparasitic effects of Artemisia abrotanum and Salvia officinalis extracts on Syphacia obvelata,Aspiculoris tetrapetra and Hymenolepis nana parasites

ObjectiveTo evaluate the effects of Salvia officinalis and Artemisia abrotanum extracts against digestive system parasites of mice.MethodsThe ethanol extract was prepared and dissolved in distilled water. The mebendazole was used as positive control and distilled water as negative control. After counting eggs per gram feces, infected mice with 16 eggs per gram feces contained two to three parasites of Syphacia obvelata, Aspicoloris terepetra and Hymenolipis nana designated in 4 groups. The first group was given extracts of Artemisia (150 mg/kg), the second group was given Salvia extract (150 mg/kg), the third group was given mebendazole (10 mg/kg) and finally the fourth group was given distilled water (2 mL/kg).ResultsThe ethanol extracts of Artemisia and Salvia plants reduced the number of parasite eggs per gram of feces. Results showed significant reduction (P-value<0.001) in the number of eggs excreted by Hymenolepis nana, Aspiculuris tetraptera, Syphacia obvelata in mice.ConclusionsThese results revealed that antiparasitic effects of Artemisia and Salvia are reasonable and these two plants might be used as antiparasitic natural products.     

In vivo effects of nonsteroidal antiinflammatory drugs on rat skin and synovial mast cell-induced vasopermeability

Using our animal model of synovial mast cell-mediated arthritis in rats, we tested the effects of 3 nonsteroidal antiinflammatory drugs (NSAIDs) (aspirin, indomethacin, and ketoprofen) and an H1 and an H2 histamine receptor antagonist (diphenhydramine and cimetidine, respectively) on synovial and dermal mast cell-induced vasopermeability. Drug effects were assessed by quantifying the leakage of radiolabeled albumin into tissues following specific antigen-initiated activation of passively sensitized dermal and synovial mast cells. The 3 NSAIDs tested had different effects on synovial and dermal mast cell-induced vasopermeability. Aspirin and indomethacin significantly increased dermal and synovial plasma exudation (P less than or equal to 0.008). Ketoprofen decreased dermal (P = 0.015), but had no effect on synovial, vascular exudation. Complete histamine H1 and H2 receptor blockade with diphenhydramine and cimetidine, respectively, substantially decreased (P less than or equal to 0.0008), but did not completely inhibit, dermal and synovial mast cell-induced vasopermeability. However, the addition of indomethacin to the combined antihistamine regimen resulted in an increase in the leakage of the radiolabel into skin and synovium (back to control levels), despite the complete blockade of H1 and H2 receptors. Results of experiments with antihistamines and indomethacin suggest that mediators other than histamine are involved in synovial mast cell-induced inflammation. Furthermore, the differential response to ketoprofen indicates that the specific antigen-stimulated mediator release profiles of dermal and synovial mast cells are different. Our finding of enhanced synovial vascular leakage in animals treated with some NSAIDs, and no such effect by other NSAIDs, perhaps explains in part the diverse effects of these agents in humans with arthritis.     

Role of IL-1b and TNF-a in the regulation of NGF in experimentally induced arthritis in mice

The aim of this study was to investigate the effects of IL-1β and TNF-α on NGF levels in the knee joint in experimentally induced arthritis in adult mice. Out data showed that IL-1β, but not TNF-α, induces an increase in NGF levels, while concomitant injection of both cytokines enhances the effect of IL-1β on NGF presence. Analysis of NGF levels in the knee joint of carrageenan- and IL-1β-induced inflammation after administration of antibodies against TNF-α supports this hypothesis. Our studies also showed that exogenous administration of NGF antibody reduces the enhanced level of TNF-α occurring in arthritic mice. This latter observation indirectly suggests that NGF is implicated in the upregulation of TNF-α in these animal models of joint inflammation. The functional significance of NGF or NGF antibody in inflammatory arthritis is discussed. Received: 16 March 1998 / Accepted: 2 July 1998     

In vivo analysis of gallstone composition by computed tomography.

In vivo computed tomography (CT) of the gallbladder was performed in 39 patients with known cholelithiasis and subsequently correlated with the chemical composition of the retrieved gallstones. Six CT patterns were identified: pattern 1, negative defect within the bile; pattern 2, nonvisualization of calculi; pattern 3, faint homogeneous central calcification; pattern 4A, thin rim of calcification; pattern 4B, thick rim of calcification; pattern 5, dense homogeneous central calcification. These CT patterns correlated well with cholesterol (p = 0.05) and calcium bilirubinate (p = 0.01) contents and CT attenuation values (p less than 0.001). The most common pattern was CT pattern 2 (56.5%). The authors conclude that there is good correlation of the CT pattern with gallstone composition. This simple approach can be used to help identify patients for therapy with chemical dissolution and/or lithotripsy.     

In vivo activity of perifosine against Leishmania amazonensis

Miltefosine has been established as the first oral administration drug against cutaneous and visceral leishmaniasis. Other alkyl-phospholipids such as edelfosine have been tested against Leishmania showing an in vitro antiparasitic activity. Perifosine in vitro activity has been previously demonstrated against different Leishmania species including Leishmania amazonensis. In this study edelfosine and perifosine were orally administered to BALB/c mice at doses of 1 and 2.5 mg/kg/day during 28 days and 5 mg/kg/day during 14 days, starting the treatment 2 weeks after the first treatment scheme. Lesion sizes and parasitic burden as well as viability were determined in order to establish the treatment effectiveness. An assay to compare miltefosine at standard dose of 2.5 mg/kg/day during 28 days to an in vivo treatment with perifosine at the most effective treatment scheme observed in this study 5 mg/kg/day during 14 days, was also developed. Perifosine showed the higher activity in the in vivo assay and is showing as a new possibility within the alkyl-phospholipids group for the treatment against cutaneous leishmaniasis caused by L. amazonensis.     

PHⅡ-7的体内外抗肿瘤活性及机制

目的研究PHⅡ-7的体内外抗肿瘤活性,为肿瘤的治疗提供新思路。方法采用MTT法检测PHⅡ-7对18种细胞系（其中包括5对敏感肿瘤细胞和相应耐药细胞株）的体外抗肿瘤活性;建立人白血病细胞K562和K562／A02裸鼠移植瘤模型,研究PHⅡ-7的体内抗肿瘤活性。结果PHⅡ-7对人肿瘤细胞的生长均有抑制作用,IC50为0．35-18．68μmol／L;其对于多药耐药（MDR）类细胞亦显示出较强的抑制作用。PHⅡ-7对耐药肿瘤细胞（K562／A02）移植瘤模型的抑制率为62％,对敏感肿瘤细胞（K562）移植瘤模型的抑制率为52％。结论PHⅡ-7体内外均可抑制肿瘤细胞的生长,其抗耐药肿瘤的作用可能存在多种机制。本研究为肿瘤的治疗提供了新思路。     

In vivo adrenocorticotropin-releasing activity of neurohypophyseal hormones and their analogs

The ability of 21 neurohypophyseal hormones and related synthetic peptides to raise plasma ACTH or corticosterone concentrations was studied in female rats anesthetized with chlorpromazine, morphine, and pentobarbital. Corticotropin-releasing factor (CRF) activity was significantly correlated with pressor but not with antidiuretic or oxytocic activity. However, peptides with little or no pressor but very potent antidiuretic activity had weak CRF activity if given in a dose greater than 4 antidiuretic units/100 g BW; the dose-response slopes of these analogs were significantly flatter than that of arginine vasopressin. Pretreatment with antagonists with antipressor but not antiantidiuretic activity consistently reduced the CRF activity of the analogs with potent pressor activity. We conclude that the CRF activity of the neurohypophyseal hormones is primarily related to pressor activity.     

In vitro effect of nonsteroidal antiinflammatory drugs on proteoglycanase and collagenase activity in human osteoarthritic cartilage.

The effects of several nonsteroidal antiinflammatory drugs, used at concentrations achievable in synovial fluid, on human osteoarthritic (OA) cartilage metallo-protease activity in vitro was studied. Acetaminophen and ketoprofen had no effect; sodium salicylate, indomethacin, and diclofenac slightly decreased proteoglycanase activity. Piroxicam and tenoxicam suppressed proteoglycanase activity by 48.2% and 68.3%, respectively, and suppressed collagenase activity by 19.1% and 36.8%, respectively. Use of these NSAIDs may help to decrease cartilage catabolism in patients with OA.     

In vivo activity of asialo-erythropoietin in combination with asialo-glycoproteins

Summary In vitro active asialo-erythropoietin has no effect on hemesynthesis in vivo. Asialo-glycophorin induces a very low ⁵⁹Fe-uptake rate in heme in exhypoxic polycythemic mice. The combination of asialo-erythropoietin and asialo-glycophorin or asialo-fetuin induced an activation comparable to the activation by native erythropoietin. Obviously the combination of asialo-erythropoietin and tested glycoproteins influence the activity of erythropoiesis-stimulating capacity of asialo-erythropoietin.Supported by the Stiftung Volkswagenwerk     

In vivo enzyme activity in inborn errors of metabolism

Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.     

In vitro activity of chloroquine and quinine in combination with desferrioxamine against Plasmodium falciparum

The activity of chloroquine and quinine, alone and in combination with desferrioxamine (7 μmol/liter), was evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum by a semimicroassay system. The addition of desferrioxamine had no effect on the activity of chloroquine against both clones. Desferrioxamine had no effect on the activity of quinine against the susceptible clone but had slightly enhanced quinine action against the resistant clone. Further development of desferrioxamine as an antimalarial drug may be of limited interest. © 1993 Wiley-Liss, Inc.     

In vitro and in vivo antitumor activity of melatonin receptor agonists

Abstract: Melatonin has been shown to inhibit the proliferation of estrogen receptor α (ERα)‐positive human breast cancer cells in vitro and suppress the growth of carcinogen‐induced mammary tumors in rats. Melatonin’s antiproliferative effect is mediated, at least in part, through the MT1 melatonin receptor and mechanisms involving modulation of the estrogen‐signaling pathway. To develop melatonin analogs with greater therapeutic effects, we have examined the in vitro and in vivo antimitotic activity of two MT1/MT2 melatonin receptor agonists, S23219‐1 and S23478‐1. In our studies, both agonists are quite effective at suppressing the growth of MCF‐7 human breast cancer cells. At a concentration of 10^?6 m , S23219‐1 and S23478‐1 inhibited the growth of MCF‐7 cells by 60% and 73%, respectively. However, S23478‐1 is more effective than melatonin and S23219‐1 at repressing the expression and transactivation of the ERα, and modulating the expression of pancreatic spasmolytic polypeptide (pS2), an estrogen‐regulated gene. The melatonin agonist S23478‐1 exhibited enhanced antitumor potency in the subsequent studies in our animal model. At a dosage of 25 mg/kg/day, S23478‐1 is more efficacious than melatonin at inducing regression of the established N‐nitroso‐N‐methyl‐urea‐induced rat mammary tumors. This dose of S23478‐1 (25 mg/kg/day) generated a significant (P < 0.05) overall regression response of 52%. Furthermore, at this dosage, S23478‐1 is more effective than melatonin at suppressing the estrogen‐signaling pathway and promoting tumor cell apoptosis, significantly increasing the expression of the pro‐apoptotic protein Bax, while decreasing the expression of ERα and the anti‐apoptotic protein Bcl‐2.     

丁酸盐与非甾体抗炎药对大肠腺癌细胞HT-29的作用

目的 观察丁酸盐和非甾体抗炎药（NSAIDs)对大肠腺癌细胞HT－29的作用,并探讨其可能的作用机制。方法 用酶联免疫法定量检测HT－29细胞所分泌的前列腺素（PG）E2;流式细胞仪检测细胞的凋亡率;电镜观察凋亡细胞的形态学。结果 丁酸盐可刺激细胞分泌大量的PGE2,阿司匹林和NS－398则抑制PGE2的分泌,3种药物均具有促进细胞凋亡的作用,且其作用呈浓度和时间依赖性（P＜0．05）;药物联用可使其作用不同程度地增强。结论 单用丁酸盐和2种NSAIDs制剂均有促凋亡作用,联用可通过下调环氧化酶－2的表达进一步增强疗效。     

河北省南水北调饮水含氟量及化学成分的调查

目的 探讨河北省南水北调中线供水区饮水氟含量与水质其它化学成分的关系及对地氟病的影响。方法 按南水北调中线供水区地方氟中毒调查实施方案要求,对51个重点村采集的近、中、远水样进行水氟含量与水总硬度、水总碱度、pH、水碘等化学成分的测定分析。结果 南水北调中线供水区水氟含量与水的硬度呈负相关,与水的总碱度、水碘含量呈正相关。结论 南水北调中线供水区水氟与水质中其它化学成分有关,对地氟病有一定影响。     

Antimicrobial activity of Algerian propolis in foodborne pathogens and its quantitative chemical composition

ObjectiveTo evaluate the antimicrobial activity of propolis samples collected from different regions of Algeria and their chemical composition.MethodsThe antibacterial activity of ethanolic extract of Algerian propolis against Bacillus cereus (IPA), Staphylococcus aureus (ATCC25923R), Escherichia coli (ATCC25922) and Pseudomonas aeruginosa (ATCC27893R) was evaluated by the disc diffusion method and determined as an equivalent of the inhibition zones diameters after incubation of the cultures at 37 °C for 24 h. The investigation of the polyphenol and flavonoid contents was done spectrophotometrically.ResultsThe ethanolic extract of Algerian propolis samples inhibited the growth of all examined microorganisms with the highest antimicrobial activity against the Gram-positive bacteria. Polyphenol and flavonoids contents were variable, depending on the propolis samples and a positive correlation between antimicrobial activity and chemical composition was observed.ConclusionsAntimicrobial activity, polyphenol and flavonoid contents were variable, depending on the propolis sample. The strong antimicrobial activity of Algerian propolis may be due to high total phenolic and flavonoid contents and this study suggests potential use of propolis in foods.