Biodegradation of trichloroethylene and toluene by indigenous microbial populations in soil.

PubMed Central

Fan, S; Scow, K M

1993-01-01

The biodegradation of trichloroethylene (TCE) and toluene, incubated separately and in combination, by indigenous microbial populations was measured in three unsaturated soils incubated under aerobic conditions. Sorption and desorption of TCE (0.1 to 10 micrograms ml-1) and toluene (1.0 to 20 micrograms ml-1) were measured in two soils and followed a reversible linear isotherm. At a concentration of 1 micrograms ml-1, TCE was not degraded in the absence of toluene in any of the soils. In combination, both 1 microgram of TCE ml-1 and 20 micrograms of toluene ml-1 were degraded simultaneously after a lag period of approximately 60 to 80 h, and the period of degradation lasted from 70 to 90 h. Usually 60 to 75% of the initial 1 microgram of TCE ml-1 was degraded, whereas 100% of the toluene disappeared. A second addition of 20 micrograms of toluene ml-1 to a flask with residual TCE resulted in another 10 to 20% removal of the chemical. Initial rates of degradation of toluene and TCE were similar at 32, 25, and 18 degrees C; however, the lag period increased with decreasing temperature. There was little difference in degradation of toluene and TCE at soil moisture contents of 16, 25, and 30%, whereas there was no detectable degradation at 5 and 2.5% moisture. The addition of phenol, but not benzoate, stimulated the degradation of TCE in Rindge and Yolo silt loam soils, methanol and ethylene slightly stimulated TCE degradation in Rindge soil, glucose had no effect in either soil, and dissolved organic carbon extracted from soil strongly sorbed TCE but did not affect its rate of biodegradation. PMID:8328806

Activities of potential therapeutic and prophylactic antibiotics against blood culture isolates of viridans group streptococci from neutropenic patients receiving ciprofloxacin.

PubMed Central

McWhinney, P H; Patel, S; Whiley, R A; Hardie, J M; Gillespie, S H; Kibbler, C C

1993-01-01

All 47 sequential blood culture isolates of viridans group streptococci obtained from febrile neutropenic patients receiving quinolone prophylaxis were susceptible to vancomycin, teicoplanin, and imipenem. Resistance to benzylpenicillin (MIC for 50% of isolates [MIC50], 0.125 microgram/ml) and ceftazidime (MIC50, 4 micrograms/ml) was common. Most isolates were susceptible to amoxicillin, co-amoxiclav (amoxicillin-clavulanic acid at a 2:1 ratio by weight), azlocillin, clarithromycin, and erythromycin, with azithromycin showing comparable activity. The MIC90 of sparfloxacin was 1 microgram/ml; those for ciprofloxacin and ofloxacin were > 16 and 16 micrograms/ml, respectively. PMID:8285642

Pharmacological studies of stonefish (Synanceja trachynis) venom.

PubMed

Hopkins, B J; Hodgson, W C; Sutherland, S K

1994-10-01

The present study was designed to examine some of the pharmacological properties of venom from the stonefish (Synanceja trachynis), with particular reference to the presence in the venom of pain-producing/enhancing substances. Stonefish venom (1-6 micrograms/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum. No tachyphylaxis, or reduction in responses with time, was observed to venom (3 micrograms/ml) in ileum. The response to venom (3 micrograms/ml) was not significantly affected by the histamine antagonist mepyramine (0.5 microM), or a preceding anaphylactic response. Mecamylamine, 5HT-desensitization or EXP3174 failed to have any significant effect on responses to venom (3 micrograms/ml). Responses to venom (3 micrograms/ml) were significantly inhibited by the cyclooxygenase inhibitor indomethacin (5 microM), the leukotriene D4 receptor antagonist FLP55712 (1 microM), the thromboxane A2 receptor antagonist GR32191B (1 microM), the muscarinic receptor antagonist atropine (10 nM) and the neurokinin-1 receptor antagonist CP96345 (0.1 microM). Venom (6 micrograms/ml) produced contractile responses in the rat isolated vas deferens which were abolished by the alpha 1-adrenoceptor antagonist prazosin (0.3 microM) and significantly potentiated by the neuronal uptake inhibitor DMI (1 microM). However, noradrenergic transmitter depletion with reserpine (5 mg/kg, i.p.) did not significantly inhibit responses to venom (6 micrograms/ml). Histamine fluorometric and phospholipase A2 assays failed to detect significant quantities of either substance in the venom. These results suggest that stonefish venom may cause the release of acetylcholine, substance P, and cyclooxygenase products, or contain components which act at these receptors. The venom also appears to contain a component which is a substrate for neuronal uptake and has a direct action at alpha 1-adrenoceptors.

Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A.

PubMed

Jagielo, P J; Quinn, T J; Qureshi, N; Schwartz, D A

1998-01-01

To further determine the importance of endotoxin in grain dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides (RsDPLA) as a partial agonist of grain dust-induced airway inflammation. RsDPLA is a relatively inactive compound compared with lipid A derived from Escherichia coli (LPS) and has been demonstrated to act as a partial agonist of LPS-induced inflammation. To assess the potential stimulatory effect of RsDPLA in relation to LPS, we incubated THP-1 cells with RsDPLA (0.001-100 micrograms/ml), LPS (0.02 microgram endotoxin activity/ml), or corn dust extract (CDE; 0.02 microgram endotoxin activity/ml). Incubation with RsDPLA revealed a tumor necrosis factor (TNF)-alpha stimulatory effect at 100 micrograms/ml. In contrast, incubation with LPS or CDE resulted in TNF-alpha release at 0.02 microgram/ml. Pretreatment of THP-1 cells with varying concentrations of RsDPLA before incubation with LPS or CDE (0.02 microgram endotoxin activity/ml) resulted in a dose-dependent reduction in the LPS- or CDE-induced release of TNF-alpha with concentrations of RsDPLA of up to 10 micrograms/ml but not at 100 micrograms/ml. To further understand the role of endotoxin in grain dust-induced airway inflammation, we utilized the unique LPS inhibitory property of RsDPLA to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. Ten micrograms of RsDPLA intratracheally did not cause a significant inflammatory response compared with intratracheal saline. However, pretreatment of mice with 10 micrograms of RsDPLA intratracheally before exposure to CDE (5.4 and 0.2 micrograms/m3) or LPS (7.2 and 0.28 micrograms/m3) resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. These results confirm the LPS-inhibitory effect of RsDPLA and support the role of endotoxin as the principal agent in grain dust causing airway inflammation.

Anti-bacterial activity of synthetic N-heterocyclic oxidizing compounds.

PubMed

Babalola, G O

1998-01-01

Synthetic chlorochromate derivatives of pyridine and quinoline were active in vitro against type cultures of Escherichia coli (ATCC 128), Staphylococcus aureus (ATCC 14775), Pseudomonas aeruginosa (ATCC 10145) and Bacillus subtilis (NCTC 8236). The minimum inhibitory concentrations (MIC) were 125-250 micrograms ml-1 and 250-500 micrograms ml-1 for pyridinium chlorochromate and quinolinium chlorochromate, respectively. An established derivative of quinoline (Perfloxacin) had an MIC of 125-250 micrograms ml-1. The extinction time for 10(5) cfu in broth was 90 min for pyridinium chlorochromate and 120 min for quinolinium chlorochromate, except for B. subtilis which survived up to about 180 min and 360 min. A combination of the two compounds produced an antagonistic effect. The 50% lethal dose (LD50 toxicity) in mice was estimated at 76 micrograms g-1 and 33 micrograms g-1 body weight for the quinolinium and pyridinium chlorochromates. The compounds also exhibited some potential for suppressing a simulated staphylococcal infection in mice at the dosage levels of ca 22 micrograms g-1 for pyridinium chlorochromate and 45 micrograms g-1 for quinolinium chlorochromate.

The influence of cimetidine on the pharmacokinetics of 5-fluorouracil.

PubMed Central

Harvey, V J; Slevin, M L; Dilloway, M R; Clark, P I; Johnston, A; Lant, A F

1984-01-01

The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for 4 weeks (1000 mg daily) led to increased peak plasma concentrations of 5FU and also area under the plasma concentration-time curve (AUC). The peak plasma concentration after oral 5FU was increased by 74% from 18.7 +/- 4.5 micrograms/ml (mean +/- s.e. mean) to 32.6 +/- 4.4 micrograms/ml (P less than 0.05) and AUC was increased by 72% from 528 +/- 133 micrograms/ml-1 min (mean +/- s.e. mean) to 911 +/- 152 micrograms ml-1 min (P less than 0.05). After intravenous 5FU, AUC was increased by 27% from 977 +/- 96 micrograms ml-1 min (mean +/- s.e. mean) to 1353 +/- 124 micrograms ml-1 min (P less than 0.01). Total body clearance for 5FU following intravenous administration was decreased by 28% from 987 +/- 116 ml/min (mean +/- s.e. mean) to 711 +/- 87 ml/min (P less than 0.01). The elimination half-life of 5FU was not altered by cimetidine. The basis of the interaction between 5FU and cimetidine is uncertain but probably a combination of inhibited drug metabolism and reduced liver blood flow. The therapeutic implications are considerable and additional care should be taken in patients receiving the two drugs concomitantly. PMID:6487480

Mutation of Chinese Hamster V79 cells and transformation and mutation of mouse fibroblast C3H/10T1/2 clone 8 cells by aflatoxin B1 and four other furocoumarins isolated from two Nigerian medicinal plants.

PubMed

Uwaifo, A O; Billings, P C; Heidelberger, C

1983-03-01

Mutation by aflatoxin B1 (AFB1), imperatorin, marmesin, chalepin, and 8-methoxypsoralen (MOP), with and without black light (BL; long-wavelength ultraviolet light) activation, was determined at the hypoxanthine-guanine phosphoribosyltransferase locus (8-azaguanine resistance) in Chinese hamster V79 cells and at the ouabain locus in mouse C3H/1OT1/2 cells. Transformation by these furocoumarins under the same activation conditions was also investigated in C3H/1OT1/2 cells. In V79 cells, AFB1 induced a 4-fold maximum mutation frequency over controls under BL activation at a concentration of 5 micrograms/ml; marmesin induced a 2-fold increased mutation frequency at 1.5 micrograms/ml; MOP induced a 19-fold increase at 10 micrograms/ml; chalepin induced a 3-fold increase at 5 micrograms/ml; and imperatorin induced a 20-fold increase at 10 micrograms/ml. Essentially no mutation was observed at the ouabain-resistant (Ouar) locus in C3H/1OT1/2 cells with any of these compounds. In the transformation assays, type II and type III foci were observed at a 1-microgram/ml addition of AFB1 with or without BL activation; while with MOP and imperatorin, these types of foci were observed only with BL activation. Marmesin, although relatively more cytotoxic than the other furocoumarins studied, with a 50% lethal dose of less than 0.5 micrograms/ml, was not as mutagenic or potentially carcinogenic as were AFB1, imperatorin, or MOP with BL activation. These furocoumarins are considered to be involved in the etiology of the high incidence of skin cancer in Nigeria. Our experiments reinforce that concept and suggest that exposure to these furocoumarins may constitute a real carcinogenic hazard.

Saponin 1 Induces Apoptosis and Suppresses NF-κB-Mediated Survival Signaling in Glioblastoma Multiforme (GBM)

PubMed Central

Tang, Chi; Li, Bo; Wang, Yuangang; Gao, Zhenhui; Luo, Peng; Yin, Anan; Wang, Xiaoyang; Cheng, Guang; Fei, Zhou

2013-01-01

Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM. PMID:24278406

[Pharmacokinetic studies of flomoxef in the neonatal field].

PubMed

Kimura, K; Miyano, T; Shimomura, H

1991-11-01

Flomoxef (FMOX), a new broad spectrum oxacephem antibiotic, was studied in the neonatal field and the pharmacokinetic results obtained are summarized below. 1. Serum concentrations of FMOX after dosages of 20 mg/kg via 1 hour drip infusion were 21.8 +/- 7.59 micrograms/ml, 15.4 +/- 4.35 micrograms/ml, 4.3 +/- 2.88 micrograms/ml at 1, 2 and 5 hours after administration, respectively, and T 2/1 (beta)'s averaged 2.08 +/- 1.01 hours. 2. Urinary excretion rates were 53.38 +/- 16.94% in the first 7 hours after administration.

[Effect of qigong exercise on the blood level of monoamine neuro-transmitters in patients with chronic diseases].

PubMed

Liu, B; Jiao, J; Li, Y

1990-04-01

In this study, the authors, by means of fluorescence spectrophotometry, observed the variations of blood contents of monoamine neuro-transmitters (5-hydroxytamine 5-HT; norepinephrine NE; dopamine DA) in 68 subjects before and after adoption of Qigong exercises. A comparison of pre- and post-exercise showed a general reduction in 5-HT, varying from 0.43 +/- 0.21 to 0.21 +/- 0.13 microgram/ml (P less than 0.001). Variations in NE and DA tended to go up, NE being from 0.27 +/- 0.13 to 0.35 +/- 0.27 microgram/ml, DA from 0.86 +/- 0.69 to 1.19 +/- 0.81 micrograms/ml (P less than 0.02). Effects of Qigong exercises on different diseases: Subjects in each group showed reduction in blood 5-HT content after they had practised Qigong exercise. (1) Cardiovascular disease: 0.47 +/- 0.34 to 0.16 +/- 0.11 microgram/ml (n = 13); (2) gastric diseases: 0.37 +/- 0.19 to 0.22 +/- 0.13 microgram/ml (n = 20); (3) joint system diseases: 0.44 +/- 0.21 to 0.18 +/- 0.13 microgram/ml (n = 10); (4) respiratory system diseases: 0.40 +/- 0.22 to 0.22 +/- 0.12 microgram/ml (n = 8); (5) other diseases (neuroasthenia, neurosis, etc.): 0.46 +/- 0.22 to 0.25 +/- 0.14 microgram/ml (n = 13). In all these groups except the fourth group, variations in 5-HT content in comparison with the pre-exercise values were respectively P less than 0.01, less than 0.01, less than 0.05, less than 0.05. The difference was obvious. The post-exercise blood content of DA in various groups rose up remarkably.(ABSTRACT TRUNCATED AT 250 WORDS)

[In vitro susceptibilities of causative organisms isolated from patients with primary respiratory tract infections to BRL 25000 (clavulanic acid/amoxicillin)].

PubMed

Deguchi, K; Fukayama, S; Nishimura, Y; Yokota, N; Tanaka, S; Oda, S; Matsumoto, Y; Ikegami, R; Sato, K; Fukumoto, T

1985-10-01

The in vitro susceptibilities of various causative organisms recently isolated from patients with primary respiratory tract infections to BRL 25000 (a formulation of amoxicillin, 2 parts, and potassium clavulanate, 1 part), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined. beta-Lactamase producing strains were detected by nitrocefin chromogenic method and PCG acidometric method. The frequency of isolation of beta-lactamase production in strains of S. aureus, H. influenzae, B. catarrhalis and K. pneumoniae was 92%, 18%, 36% and 98%, respectively. Against S. aureus strains with MIC values to AMPC of less than or equal to 100 micrograms/ml and CEX of less than or equal to 25 micrograms/ml BRL 25000 showed MIC values in the range 0.39-6.25 micrograms/ml with inocula of 10(6) CFU/ml, while BRL 25000 required 12.5-100 micrograms/ml of concentrations for inhibition of the strains with MIC values to AMPC of greater than 100 micrograms/ml and CEX of greater than or equal to 25 micrograms/ml. Against S. pyogenes and S. pneumoniae BRL 25000 showed MIC values in the range less than 0.024-0.10 micrograms/ml with inocula of 10(6) CFU/ml, which is much more active than CCL, CEX, CDX and CXD and slight less active than AMPC. Against H. influenzae and B. catarrhalis BRL 25000 showed MIC values in the range 0.20-6.25 micrograms/ml with inocula of 10(6) CFU/ml, which showed most potent activity among the agents tested. The activity of BRL 25000 against K. pneumoniae was approximately equal to that of CCL and superior to that of AMPC, CEX, CDX and CXD.

In vitro activity of flomoxef compared to moxalactam, cefoxitin, cefotaxime, and clindamycin against anaerobes.

PubMed

Werner, H; Heizmann, W; Luft, G

1988-11-01

To assess the in vitro activity of flomoxef (6315-S), moxalactam, cefoxitin, cefotaxime, and clindamycin against anaerobes 197 clinical isolates (27 Bacteroides fragilis, 42 B. thetaiotaomicron, 10 B. vulgatus, 7 B. ovatus, 6 B. uniformis, 6 B. distasonis, 7 Bacteroides melaninogenicus group, 11 Bacteroides oralis group, 21 Clostridium difficile, 7 C. perfringens, 3 C. sporogenes, 3 Clostridium spp., 33 Propionibacterium acnes, 14 Peptococcaceae) were studied by means of agar dilution tests. The MIC90 of B. fragilis was less than 2 micrograms/ml for flomoxef, less than 4 micrograms/ml for moxalactam, less than 16 micrograms/ml for cefoxitin, less than 128 micrograms/ml for cefotaxime and less than 2 micrograms/ml for clindamycin. The respective MIC90's of B. thetaiotaomicron were less than 64, less than 128, less than 32, less than 256 and 8 micrograms/ml. Strains of the other Bacteroides species and groups were more susceptible to flomoxef and the other antibiotics than B. thetaiotaomicron. Against Clostridium difficile flomoxef (MIC90 less than 4 micrograms/ml) proved to be superior to the other agents tested. Most of the Clostridium strains other than C. difficile were also susceptible to flomoxef; anaerobic grampositive cocci and Propionibacterium acnes were very sensitive (MIC90's less than 1 and less than or equal to 0.125 micrograms/ml, respectively). Its anti-anaerobic activity, together with its efficacy against aerobes, should make flomoxef a useful adjunct to the arsenal of modern antibiotic therapy.

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Inhibition of inducible nitric oxide synthase expression by novel nonsteroidal anti-inflammatory derivatives with gastrointestinal-sparing properties.

PubMed Central

Cirino, G.; Wheeler-Jones, C. P.; Wallace, J. L.; Del Soldato, P.; Baydoun, A. R.

1996-01-01

1. The effects of novel nitric oxide-releasing nonsteroidal anti-inflammatory compounds (NO-NSAIDs) on induction of nitric oxide (NO) synthase by bacterial lipopolysaccharide (LPS) were examined in a murine cultured macrophage cell line, J774. 2. LPS-induced nitrite production was markedly attenuated by the nitroxybutylester derivatives of flurbiprofen (FNBE), aspirin, ketoprofen, naproxen, diclofenac and ketorolac, with each compound reducing accumulated nitrite levels by > 40% at the maximum concentrations (100 micrograms ml-1) used. 3. Further examination revealed that nitrite production was inhibited in a concentration-dependent (1-100 micrograms ml-1) manner by FNBE which at 100 micrograms ml-1 decreased LPS-stimulated levels by 63.3 +/- 8.6% (n = 7). The parent compound flurbiprofen was relatively ineffective over the same concentration-range, inhibiting nitrite accumulation by 24 +/- 0.9% (n = 3) at the maximum concentration used (100 micrograms ml-1). 4. FNBE reduced LPS-induced nitrite production when added to cells up to 4 h after LPS. Thereafter, FNBE caused very little or no reduction in nitrite levels. Furthermore NO-NSAIDs (100 micrograms ml-1) did not inhibit the metabolism of L-[3H]-arginine to citrulline by NO synthase isolated from LPS-activated macrophages. 5. Western blot analysis demonstrated that NO synthase expression was markedly attenuated following co-incubation of J774 cell with LPS (1 microgram ml-1; 24 h) and FNBE (100 micrograms ml-1; 24 h). Thus taken together, these findings indicate that NO-NSAIDs inhibit induction of NO synthase without directly affecting enzyme activity. 6. In conclusion our results indicate that NO-NSAIDs can inhibit the inducible L-arginine-NO pathway, and are capable of suppressing NO synthesis by inhibiting expression of NO synthase. The clinical implications of these findings remain to be established. Images Figure 4 PMID:8730734

Relative resistance to erythromycin in Chlamydia trachomatis.

PubMed Central

Mourad, A; Sweet, R L; Sugg, N; Schachter, J

1980-01-01

Recent Chlamydia trachomatis isolates were tested in a tissue culture system for susceptibility to tetracycline, erythromycin, rosaramicin, rifampin, and clindamycin. Rifampin was the most active drug (minimal inhibitory concentration, less than or equal to 0.02 microgram/ml). Tetracycline and rasaramicin were highly active, with a concentration of less than or equal to 0.25 microgram/ml being chlamydicidal. Clindamycin was least active on a weight basis, requiring up to 16 microgram/ml to prevent the passage of chlamydiae into a drug-free tissue culture system. Relative resistance to erythromycin was detected; two isolates were capable of limited replication in 1 microgram/ml. PMID:7447426

Antioxidant and Inhibitory Effects of Saponin Extracts from Dianthus basuticus Burtt Davy on Key Enzymes Implicated in Type 2 Diabetes In vitro.

PubMed

Nafiu, Mikhail Olugbemiro; Ashafa, Anofi Omotayo Tom

2017-01-01

Dianthus basuticus is a plant of South African origin with various acclaimed pharmaceutical potentials. This study explored the antioxidant and antidiabetic activities of saponin extract from D. basuticus in vitro . Antioxidant activity of saponin was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (*NO)-free radical scavenging activity while antidiabetic potentials were measured by the α-amylase and α-glucosidase inhibitory activities of the saponin extract. The results showed that the saponin extract, compared with quercetin, displayed better DPPH (IC 50 = 6.95 mg/ml) and NO (IC 50 = 3.31 mg/ml) radical scavenging capabilities. Similarly, the saponin extracts elicited stronger α-glucosidase (IC 50 = 3.80 mg/ml) and moderate α-amylase (IC 50 = 4.18 mg/ml) inhibitory activities as compared to acarbose. Saponin exhibited a competitive mode of inhibition on α-amylase with same maximum velocity (Vmax) of 0.0093 mM/min for saponin compared with control 0.0095 mM/min and different the Michaelis constant (Km) values of 2.6 × 10 -6 mM and 2.1 × 10 -5 mM, respectively, while for α-glucosidase, the inhibition was uncompetitive, Vmax of 0.027 mM/min compared with control 0.039 mM/min and Km values of 1.02 × 10 -6 mM and 1.38 × 10 -6 mM, respectively. The gas chromatography-mass spectrometric analysis revealed the presence of bioactive like β- and α-amyrin, 3-O-methyl-D-glucose, methyl commate, and olean-12-en-3-beta-ol. Overall, the data suggested that the saponin extract from D. basuticus has potentials as natural antioxidants and antidiabetics. Saponin extract from Dianthus basuticus displayed promising antidiabetic and antioxidant activitySaponin competitively and uncompetitively inhibited a-amylase and a-glucosidase, respectivelyThe stronger inhibition of α-glucosidase and moderate inhibition of α-amylase by saponin extract from D. basuticus is promising good antidiabetes compared with existing drugs with associated side effects. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, Km: The Michaelis constant, Vmax: Maximum velocity, ROS: Reactive oxygen species, NIDDM: Non-insulin-dependent diabetes mellitus, UFS: University of the Free State, GC-MS: Gas chromatography-mass spectrometric, MS: Mass spectrometry, NIST: National Institute of Standards and Technology, DNS: 3,5-dinitrosalicylic acid, NO: Nitric oxide, RNS: Reactive nitrogen species, PNPG: p-Nitrophenyl-α-D-glucopyranoside.

Antioxidant and Inhibitory Effects of Saponin Extracts from Dianthus basuticus Burtt Davy on Key Enzymes Implicated in Type 2 Diabetes In vitro

PubMed Central

Nafiu, Mikhail Olugbemiro; Ashafa, Anofi Omotayo Tom

2017-01-01

Context: Dianthus basuticus is a plant of South African origin with various acclaimed pharmaceutical potentials. Aims: This study explored the antioxidant and antidiabetic activities of saponin extract from D. basuticus in vitro. Materials and Methods: Antioxidant activity of saponin was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (*NO)-free radical scavenging activity while antidiabetic potentials were measured by the α-amylase and α-glucosidase inhibitory activities of the saponin extract. Results: The results showed that the saponin extract, compared with quercetin, displayed better DPPH (IC50 = 6.95 mg/ml) and NO (IC50 = 3.31 mg/ml) radical scavenging capabilities. Similarly, the saponin extracts elicited stronger α-glucosidase (IC50 = 3.80 mg/ml) and moderate α-amylase (IC50 = 4.18 mg/ml) inhibitory activities as compared to acarbose. Saponin exhibited a competitive mode of inhibition on α-amylase with same maximum velocity (Vmax) of 0.0093 mM/min for saponin compared with control 0.0095 mM/min and different the Michaelis constant (Km) values of 2.6 × 10-6 mM and 2.1 × 10-5 mM, respectively, while for α-glucosidase, the inhibition was uncompetitive, Vmax of 0.027 mM/min compared with control 0.039 mM/min and Km values of 1.02 × 10-6 mM and 1.38 × 10-6 mM, respectively. The gas chromatography-mass spectrometric analysis revealed the presence of bioactive like β- and α-amyrin, 3-O-methyl-D-glucose, methyl commate, and olean-12-en-3-beta-ol. Conclusion: Overall, the data suggested that the saponin extract from D. basuticus has potentials as natural antioxidants and antidiabetics. SUMMARY Saponin extract from Dianthus basuticus displayed promising antidiabetic and antioxidant activitySaponin competitively and uncompetitively inhibited a-amylase and a-glucosidase, respectivelyThe stronger inhibition of α-glucosidase and moderate inhibition of α-amylase by saponin extract from D. basuticus is promising good antidiabetes compared with existing drugs with associated side effects. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, Km: The Michaelis constant, Vmax: Maximum velocity, ROS: Reactive oxygen species, NIDDM: Non-insulin-dependent diabetes mellitus, UFS: University of the Free State, GC-MS: Gas chromatography-mass spectrometric, MS: Mass spectrometry, NIST: National Institute of Standards and Technology, DNS: 3,5-dinitrosalicylic acid, NO: Nitric oxide, RNS: Reactive nitrogen species, PNPG: p-Nitrophenyl-α-D-glucopyranoside. PMID:29200716

[The study of flomoxef in the pediatric field].

PubMed

Sato, H; Narita, A; Nakazawa, S; Suzuki, H; Mastumoto, K; Nakanishi, Y; Nakazawa, S; Niino, K; Nakada, Y

1987-08-01

Flomoxef (FMOX; 6315-S), a new synthetic oxacephem antibiotic, was studied in the pediatric field and pharmacokinetic and clinical results obtained were summarized below. 1. The activity of FMOX against Staphylococcus aureus isolated from clinical patients, including latamoxef resistant strains was very high and MIC was approximately less than or equal to 0.39 microgram/ml. This MIC value was lower than other cephem antibiotics such as cefotaxime, cefotiam, cefmetazole, cefamandole. The distribution of MIC's of FMOX against Escherichia coli and Salmonella spp. ranged from 0.05 to 0.78 microgram/ml and from 0.05 to 0.39 microgram/ml, respectively. 2. Serum concentrations of FMOX after dosages of 20 mg/kg and 40 mg/kg with 1 hour intravenous drip infusion were 21.5-27.5 micrograms/ml, 6.00-7.81 micrograms/ml, 0.37-0.59 micrograms/ml at 1, 2, 5 hours after administration, respectively, and T1/2(beta) were 0.61-0.83 hour. Serum concentrations after one shot intravenous injection of 20 mg/kg FMOX were 56.7-90.2 and 0.20-0.26 micrograms/ml at 3-10 minutes and 6 hours after administration, respectively, T1/2(beta) was 1.22 hours and urinary excretion rate was 66.7-69.8% in 6 hours. 3. FMOX was administered to 32 cases (upper and lower respiratory tract infection, and purulent infections) at 3-4 times daily for 4-13 days. In these cases the daily dosage amounted to 41-119 mg/kg. Clinical effectiveness was 97% overall including resistance cases upon other cephem antibiotic treatment. All bacterial species identified including Branhamella catarrhalis, Streptococcus pyogenes, S. aureus, Streptococcus agalactiae, and Haemophilus influenzae were eradicated upon the treatment with FMOX. 4. Only 3 cases of soft stool, 1 case of elevated GOT and GPT, and 1 case of elevated GPT were observed, and all of these adverse reactions were normalized after the completion of treatment.

Bioequivalence of clavulanate potassium and amoxicillin (1:7) dispersible tablets in healthy volunteers.

PubMed

Hu, Guoxin; Dai, Zongshun; Long, Lihong; Han, Ying; Hou, Shuxian; Wu, Li

2002-01-01

To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross-over study was conducted in 18 healthy volunteers. A single oral dose of 1,000 mg Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main parameters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46 +/- 1.11 micrograms/ml and 18.81 +/- 7.26 micrograms/ml, Tmax: 1.12 +/- 0.23 h and 1.30 +/- 0.34 h, AUC(0-6 h): 5.18 +/- 2.24 micrograms.h/ml and 45.09 +/- 14.53 micrograms.h/ml, t1/2: 1.43 +/- 0.44 h and 1.09 +/- 0.22 h., respectively. The relative bioavailability of T to R were 96.5 +/- 19.2% and 98.4 +/- 26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

PubMed

Matsuo, K; Uete, T

1992-10-01

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

1992-01-01

We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

[Study on active constituents of traditional Chinese medicine reversing multidrug resistance of tumor cells in vitro].

PubMed

Zhang, H; Yang, L; Liu, S; Ren, L

2001-09-01

To screen drugs reversing multidrug resistance of tumor cells from active constituents of traditional Chinese medicine and to study the reversal action. The kill effects of the drugs on tumor cell lines in vitro were determined with MTT method. The Jin's formula was used to analyse the effect of drug combination. 5 micrograms/ml rhynchophylline, 2 micrograms/ml jatrorrhizine and 1.25 micrograms/ml indirulin could reverse multidrug resistance for vincristine on KBv200 cell line by 16.8, 5.1 and 4 fold respectively. 1.56-12.5 micrograms/ml curcumine combining with vincristine could sensitize antitumor effect both on KB and KBv200 cell lines. All rhynchophylline, jatrorrhizine and indirulin could reverse multidrug resistance for vincristine on KBv200 cell line. Curcumine combinating vincristine could sensitize antitumor effect both on kB and kBv200 cell lines.

[Pharmacokinetic and clinical studies on flomoxef in the perinatal period in obstetrics and gynecology].

PubMed

Yamamoto, T; Yasuda, J; Okada, H; Iwasaku, K

1991-06-01

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period in obstetrics and gynecology were performed and the results obtained are summarized as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined after intravenous injection of 1 g. The maternal serum concentration was 41.9 micrograms/ml at 16 minutes after administration, and gradually decreased thereafter to 1.36 micrograms/ml at 5 hours 19 minutes. The concentration of FMOX in umbilical cord serum was 17.5 micrograms/ml at 16 minutes after administration, then gradually decreased thereafter, was slightly higher than that in maternal serum after approx. 3 hours and was 2.88 micrograms/ml at 5 hours 19 minutes. The amniotic fluid concentration was 0.31 micrograms/ml at 16 minutes after administration, increased to 7.85-15.8 micrograms/ml at approx. 3 hours, and gradually decreased while maintaining relatively high levels. 2. One or two grams of FMOX were given by intravenous drip infusion twice daily to 17 patients with perinatal infections for 5 to 7 days. Clinical efficacies were evaluated as excellent in 7 cases and good in 10, suggesting that FMOX was effective in all cases. No subjective side effects were observed in any of the 17 patients. As to abnormal laboratory findings, a minor degree of elevation of GPT was observed in 1 patient and that of GOT.GPT in 1. No other abnormal changes in laboratory examinations were observed. Considering the above results, we conclude that FMOX is a useful antibiotic in perinatal infections.

[Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from animals to ofloxacin and commonly used antimicrobial agents].

PubMed

Takahashi, I; Yoshida, T; Higashide, Y; Sakano, T

1990-01-01

Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from chickens, pigs and cattle to ofloxacin (OFLX) and commonly used antimicrobial agents were investigated. 1. E. coli (28 isolates) demonstrated the highest level of susceptibility of OFLX (MIC 0.10-0.39 micrograms/ml for all the isolates) among all the test drugs. Commonly used antimicrobial agents to which these isolates responded with relatively high susceptibilities (MIC50 0.78-6.25 micrograms/ml) included oxolinic acid (OXA), ampicillin (ABPC), kanamycin (KM) and chloramphenicol (CP) with their MIC50 values in the increasing order as above. Drugs to which these isolates responded with moderate to weak susceptibilities (MIC50 25 approximately greater than 800 micrograms/ml) were doxycycline (DOXY), streptomycin (SM), spectinomycin (SPCM) and sulfadimethoxine (SDMX) in the increasing order of MIC50. E. coli isolates with resistances to all the test drugs other than OFLX and OXA amounted to 7.1-57.1% of the isolates examined and 20 isolates (71.4%) in total. 2. Susceptibilities to OFLX and 4 existing pyridonecarboxylic acid derivatives of E. coli (48 samples) isolated recently from diarrheal pigs were compared. When evaluated in terms of MIC50, the values of OFLX and norfloxacin were both 0.10 micrograms/ml. The values increased by differences of 0.39-3.13 micrograms/ml in an order of OXA, pipemidic acid and nalidixic acid. 3. Salmonella (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.20-0.39 micrograms/ml for all the isolates) among all the test drugs. The drugs to which these isolates responded with relatively high to moderate susceptibilities (MIC50 0.78-12.5 micrograms/ml) included ABPC, OXA, DOXY, KM, CP and SM with their MIC50 values increasing in this order. The drugs to which the isolates responded with low susceptibilities (MIC50 above 100 micrograms/ml) were SPCM and SDMX. Of all the 28 Salmonella isolates tested, 7.1-32.1% were resistant to all the test drugs other than OFLX and OXA. These resistant isolates amounted to a total of 12 isolates (42.9%). 4. S. aureus (28 isolates) were highly susceptible to OFLX (MIC50 and MIC90 were both 0.78 micrograms/ml). Commonly used antimicrobial agents to which the isolates responded with high to relatively high susceptibilities (MIC50 0.10-6.25 micrograms/ml) were, in the increasing order of MIC50: DOXY, ABPC, tylosin, tiamulin, KM, OXA and CP. Drugs with moderate to low bacterial susceptibilities (MIC50 12.5-100 microns/ml) were SD, SDMX and SPCM. Isolates resistant to all the test drugs except OFLX and SDMX amounted to 3.6-50% of the 28 isolates examined and they totalled 20 isolates (71.4%).(ABSTRACT TRUNCATED AT 400 WORDS)

Metronidazole excretion in human milk and its effect on the suckling neonate.

PubMed Central

Passmore, C M; McElnay, J C; Rainey, E A; D'Arcy, P F

1988-01-01

1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast-feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty-five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml-1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml-1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml-1 to 2.41 micrograms ml-1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml-1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast-feed their infants. PMID:3203060

In-Vitro Activity of Saponins of Bauhinia Purpurea, Madhuca Longifolia, Celastrus Paniculatus and Semecarpus Anacardium on Selected Oral Pathogens

PubMed Central

Jyothi, K. S.; Seshagiri, M.

2012-01-01

Objective: Dental caries, periodontitis and other mucosal diseases are caused by a complex community of microorganisms. This study aimed to investigate the antimicrobial properties of saponins of four important oil yielding medicinal plant extracts on selected oral pathogens that are involved in such diseases. Materials and Methods: Saponins were extracted from Bauhinia purpurea, Madhuca longifolia, Celastrus paniculatus and Semecarpus anacardium and purified. Antimicrobial properties of these saponins against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Staphylococcus aureus and Lactobacillus acidophilus were determined using well diffusion method. The minimum inhibitory concentration (MIC) was determined as the lowest concentration of saponins inhibiting bacterial growth after 14 h of incubation at 37°C. The bactericidal activity was evaluated using the viable cell count method. Results: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Madhuca longifolia saponin on Streptococcus mutans MTCC 890, Streptococcus mitis and Staphylococcus aureus was 18.3 ± 0.15/34.4 ± 0.24 μg/ml, 19.0 ± 0.05/32.2 ± 0.0 μg/ml and 21.2 ± 0.35/39.0 ± 0.30 μg/ml, respectively and Bauhinia purpurea saponin on Streptococcus mutans MTCC 890, Staphylococcus aureus and Lactobacillus acidophilus was 26.4 ± 0.20/43.0 ± 0.40 μg/ml, 29.0 ± 0.30/39.6 ± 0.12 μg/ml and 20.2 ± 0.05/36.8 ± 0.23 μg/ml, respectively. Conclusion: The strong antimicrobial activity of Madhuca longifolia and Bauhinia purpurea may be due to the presence of complex triterpenoid saponins, oleanane type triterpenoid glycosides or atypical pentacyclic triterpenoid saponin. Hence, these extracted saponins may be used in food and oral products to prevent and control oral diseases. PMID:23323183

[Bacteriological and clinical studies on flomoxef in the pediatric field].

PubMed

Sunakawa, K; Ishizuka, Y; Kawai, N; Saito, N; Iwata, S; Sato, Y; Akita, H; Kusano, S; Aoki, T

1987-08-01

Bacteriological and clinical studies on flomoxef (FMOX, 6315-S) were performed and the results obtained are summarized below. 1. The MIC values of FMOX against 307 clinically isolated strains of Staphylococcus aureus were 0.024 to 100 micrograms/ml with a peak MIC of 0.39 microgram/ml, and the MIC90 value was 1.56 micrograms/ml. The MIC90 against methicillin resistant S. aureus (MRSA) was 25 micrograms/ml. 2. FMOX was administered to 15 children with pediatric bacterial infections, and the effectiveness was rated excellent or good in all cases. 3. In bacteriological evaluation, 7 of 11 strains identified prior to the treatment were eliminated (63.6%). 4. As side effects, diarrhea or soft stool was found in 3 cases and eruption in 1 case. As abnormal laboratory values, eosinophilia and thrombocytosis were found in 1 case each. 5. On the intestinal bacterial flora, FMOX had a marked influence just as did other Group 4 and 5 cephems antibiotics. 6. FMOX interfered little with the coagulation system or platelet aggregation.

In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin.

PubMed

Kim, Doo; Kordick, Dorsey; Divers, Thomas; Chang, Yung Fu

2006-12-01

Antimicrobial susceptibility testing was conducted with 6 different spirochetal strains (4 strains of Leptospira spp. and 2 strains of Borrelia burgdorferi) against 3 antimicrobial agents, commonly used in equine and bovine practice. The ranges of MIC and MBC of amoxicillin against Leptospira spp. were 0.05 - 6.25 microgram/ml and 6.25 - 25.0 microgram/ml, respectively. And the ranges of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of amoxicillin against B. burgdorferi were 0.05 - 0.39 microgram/ml and 0.20 - 0.78 microgram/ml, respectively. The ranges of MIC and MBC of enrofloxacin against Leptospira spp. were 0.05 - 0.39 microgram/ml and 0.05 - 0.39 microgram/ml, respectively. Two strains of B. burgdorferi were resistant to enrofloxacin at the highest concentration tested for MBC (>or=100 microgram/ml). Therefore, the potential role of tilmicosin in the treatment of leptospirosis and borreliosis should be further evaluated in animal models to understand whether the in vivo studies will confirm in vitro results. All spirochetal isolates were inhibited (MIC) and were killed (MBC) by tilmicosin at concentrations below the limit of testing (

High-level penicillin resistance and penicillin-gentamicin synergy in Enterococcus faecium.

PubMed Central

Torres, C; Tenorio, C; Lantero, M; Gastañares, M J; Baquero, F

1993-01-01

Thirty-seven Enterococcus faecium strains with different levels of penicillin susceptibility were studied in time-kill experiments with a fixed concentration (5 micrograms/ml) of gentamicin combined with different penicillin concentrations (6 to 600 micrograms/ml). Synergy was defined as a relative decrease in counts of greater than 2 log10 CFU per milliliter after 24 h of incubation when the combination of the antibiotics was compared with its most active component alone. The minimal synergistic penicillin concentrations found were 6 micrograms/ml for 16 of 16 strains for which penicillin MICs were < or = 25 micrograms/ml, 20 to 100 micrograms/ml for 14 of 17 strains for which penicillin MICs were 50 to 200 micrograms/ml, and 200 to 500 micrograms/ml for 4 of 4 strains for which MICs penicillin were > 200 micrograms/ml. Penicillin-gentamicin synergy was observed even in high-level penicillin-resistant E. faecium strains at penicillin concentrations close to one-half the penicillin MIC. The possibility of treating infections caused by high-level penicillin-resistant E. faecium strains with penicillin-gentamicin combinations in particular cases may depend on the penicillin levels attainable in vivo. PMID:8285628

A stimulatory effect of Artemisia leaf extract on the proliferation of cultured endothelial cells.

PubMed

Kaji, T; Kaga, K; Miezi, N; Ejiri, N; Sakuragawa, N

1990-02-01

To investigate the effect of the hot water extract from Artemisia leaf (Artemisia princeps Panpanini) (AFE) on the proliferation of endothelial cells, the cells from bovine aorta were cultured for up to 96 h in the presence of 1, 5, 10 or 50 micrograms/ml AFE in RPMI1640 medium supplemented with 10% fetal bovine serum. After a 72 h culture, the cell number was significantly increased by AFE at 1, 5 and 10 micrograms/ml. An increase in the cell number by 5 micrograms/ml AFE observed after a 72 or 96 h treatment. The incorporations of both [3H]thymidine and [14C]leucine by the growing cells were significantly increased by 5 micrograms/ml AFE after a 72 h treatment. In addition, the incorporation of [3H]thymidine by either growing or confluent cells was significantly increased by 50 micrograms/ml AFE after a 72 h treatment. The stimulatory activity of AFE was recognized in the low-molecular-weight fraction (molecular weight less than or equal to 10000 dalton). These results clearly indicated that AFE contained some low-molecular-weight component(s) which stimulates the proliferation of vascular endothelial cells in vitro.

Pharmacokinetics of cephem antibiotics in exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy.

PubMed Central

Ito, K; Hayasaki, M; Tamaya, T

1990-01-01

Many cephalosporin antibiotics have recently been invented and attempts have been made to use them clinically. The choice of which of these drugs should be used has been difficult in gynecology. The efficacies of these drugs depend on their antibacterial spectra, potencies, and concentrations in tissues. This study was designed to investigate the pharmacokinetics of various cephem antibiotics in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. These cephem antibiotics were cefoxitin, cefotiam, cefotetan, cefpiramide, cefminox, cefotaxime, ceftizoxime, cefoperazone, cefmenoxime, cefbuperazone, ceftazidime, cefpimizole, flomoxef, and cefuzonam. The maximum concentrations after administration of a 1-g dose in the exudate of the pelvic retroperitoneal space were 37.9 micrograms/ml with cefminox, 30.3 micrograms/ml with cefpimizole, 21.6 micrograms/ml with flomoxef, 21.5 micrograms/ml with ceftazidime, and 17.6 micrograms/ml with cefbuperazone, which were relatively high. When selecting antibiotics for prophylactic use against infections in the retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy, on the basis of drug transfer, flomoxef, cefminox, cefbuperazone, ceftazidime, and cefpimizole were considered to be the drugs of first choice at a dose of 1 g. PMID:2393276

[Laboratory and clinical evaluations of flomoxef sodium in neonates].

PubMed

Iwai, N; Nakamura, H; Miyazu, M; Kasai, K; Watanabe, Y; Taneda, Y; Ozaki, T; Matsui, S; Maki, T; Tauchi, N

1991-11-01

Flomoxef sodium (FMOX) was evaluated experimentally and clinically in neonates. 1. Serum concentrations and urinary excretions of the drug were examined after a bolus intravenous injection at 20 mg/kg to 22 neonates 1-30 days after birth (durations of pregnancy 31-43 weeks, weights at birth 1,650-4,040 g) and 5 infants 50-95 days after birth (durations of pregnancy 33-40 weeks, weights at birth 1,720-3,308 g). Serum concentrations were 10.8-67.6 micrograms/ml (mean 32.7 +/- 2.8 micrograms/ml) and 25.1-52.0 micrograms/ml (mean 38.9 +/- 4.3 micrograms/ml) in the neonates and the infants, respectively, at their peaks (0.5 hour value), decreased thereafter with half-lives of 0.96-5.59 hours (mean 2.20 +/- 0.26 hours value), and 0.97-1.54 hours (mean 1.22 +/- 0.12 hours value), respectively. Serum levels decreased to 0.2-17.1 micrograms/ml (mean 2.9 +/- 0.6 micrograms/ml) and N.D. -1.1 micrograms/ml (mean 0.4 +/- 0.2 micrograms/ml) after 8 hours, respectively. The urinary recovery rates of the drug in the first 8 hours after administration were 15.0-96.0% (mean 53.7 +/- 4.9%) and 29.9-73.3% (mean 62.4 +/- 9.4%) in the neonates and in the infants, respectively. 2. FMOX was administered to 78 neonates (durations of pregnancy 31-42 weeks, weights at birth 1,420-3,860 g) in whom bacterial infections were established or suspected, and clinical, bacteriological, and side effects were evaluated. In 47 neonates examined (1 with sepsis, 3 with acute upper respiratory infections, 18 with acute pneumonia, 1 with umbilical infection, 1 with impetigo, 4 with acute urinary tract infections, 1 with acute otitis externa, 1 with periproctal abscess, and 17 with intrauterine infections), the treatment was markedly effective in 41, and effective in 6, with an overall efficacy rate of 100%. The bacterilogical effects of the drug on 3 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 1 strain of Streptococcus agalactiae, 9 strains of Escherichia coli, and 2 strains of Haemophilus influenzae which were responsible for these infections were all rated as "eradicated". Moreover, the drug, administered with or without prophylactic intentions showed complete prophylactic effects in all 27 cases tested. No side effects were observed in any of the patients. Concerning abnormal clinical laboratory results, increases in GOT were noted in 2, eosinophilia in 1, and thrombocytosis in 1, but these abnormalities were invariably mild and the normalized in 1 patient without treatment. The results suggest that FMOX is useful and safe also in neonates.

In vitro studies of the antirhinovirus activity of soluble intercellular adhesion molecule-1.

PubMed Central

Arruda, E; Crump, C E; Marlin, S D; Merluzzi, V J; Hayden, F G

1992-01-01

We studied the in vitro antirhinovirus activity of a soluble form of intercellular adhesion molecule-1 (sICAM-1). sICAM-1 inhibited the cytopathic effect of 10 representative human rhinovirus (HRV) serotypes of the major receptor group with, 50% effective concentrations (EC50s) of 0.1 to 7.9 micrograms/ml. Cell type-dependent variation in the inhibitory activity of sICAM-1 was observed for two major receptor group serotypes in HeLa cells (EC50, greater than 32 micrograms/ml), and no inhibitory effect was observed for two serotypes which use different cell receptors. Yield reduction assays showed that sICAM-1 inhibited the replication of HRV serotype 39 (HRV-39) in human adenoid explants in a concentration-dependent manner. No direct inactivation of infectivity of HRV-39 (EC50, 0.5 microgram/ml) was observed after incubation with sICAM-1 (32 micrograms/ml) for up to 24 h. Single-cycle-of-replication experiments with the addition of sICAM-1 at 10 micrograms/ml at different times showed that the inhibitory effect occurs only when sICAM-1 is added within 30 min after infection. In experiments in which absorption was carried out at 4 degrees C and then a single cycle of replication incubation was carried out at 33 degrees C, it was found that sICAM-1 at 10 micrograms/ml was inhibitory only when it was present during the absorption period. Our data show that sICAM-1 is inhibitory for representative major receptor group serotypes of HRV in two cell lines and human respiratory epithelium, that the interaction of sICAM-1 with HRV is readily reversible by dilution, and that the inhibitory effect of sICAM-1 on virus replication is present early in the infection cycle. PMID:1358025

[Laboratory and clinical study of intravenous miconazole].

PubMed

Sawae, Y; Okada, K; Kumagai, Y

1987-02-01

Laboratory and clinical study was carried out on miconazole (MCZ), a new synthetic imidazole. The antifungal activity of MCZ was studied and expressed as MICs for clinical isolates. The drug proved to have the highest activity against Cryptococcus neoformans, with MICs of no more than 0.16 micrograms/ml for all isolates of this species. MICs of Torulopsis glabrata were 0.08-5 micrograms/ml for all isolates and those of Candida albicans and Candida tropicalis were 5-20 micrograms/ml for more than 90% of the isolates. Most of other strains were less than 10 micrograms/ml. When 3 healthy adult men were administered each with 200 mg of MCZ by intravenous drip infusion for 1.25 hours, the mean serum MCZ concentration was 1.39 micrograms/ml at the end of the infusion, then decreased rapidly to 0.49 microgram/ml in following 30 minutes, and then decreased gradually to 0.17 microgram/ml 6 hours later. The mean cumulative urinary excretion rate of the drug was as low as 3.0% at this stage. A total of 25 patients with ages of 30-78 years, comprising 17 men and 8 women, were treated with 200-1,800 mg of MCZ daily for 3-93 days. The clinical effectiveness was ascertained in 19 cases among the patients; 9 cases with candidiasis, 3 with cryptococcosis and 7 with aspergillosis. Clinical responses were excellent in 2, good in 9 and poor in 8 cases, and its efficacy rates was 58%. The efficacy rate of the combination therapy with other antifungal agents was 60% in comparison with 57% of MCZ alone. Adverse reactions to the drug such as nausea, vomiting and anorexia were observed in 3 cases (12%). Abnormal changes in laboratory parameters were also observed: 3 patients with elevations of GOT and GPT, and another with eosinophilia.

Effects of nisin and temperature on survival, growth, and enterotoxin production characteristics of psychrotrophic Bacillus cereus in beef gravy.

PubMed

Beuchat, L R; Clavero, M R; Jaquette, C B

1997-05-01

The presence of psychrotrophic enterotoxigenic Bacillus cereus in ready-to-serve meats and meat products that have not been subjected to sterilization treatment is a public health concern. A study was undertaken to determine the survival, growth, and diarrheal enterotoxin production characteristics of four strains of psychrotrophic B. cereus in brain heart infusion (BHI) broth and beef gravy as affected by temperature and supplementation with nisin. A portion of unheated vegetative cells from 24-h BHI broth cultures was sensitive to nisin as evidenced by an inability to form colonies on BHI agar containing 10 micrograms of nisin/ml. Heat-stressed cells exhibited increased sensitivity to nisin. At concentrations as low as 1 microgram/ml, nisin was lethal to B. cereus, the effect being more pronounced in BHI broth than in beef gravy. The inhibitory effect of nisin (1 microgram/ml) was greater on vegetative cells than on spores inoculated into beef gravy and was more pronounced at 8 degrees C than at 15 degrees C. Nisin, at a concentration of 5 or 50 micrograms/ml, inhibited growth in gravy inoculated with vegetative cells and stored at 8 or 15 degrees C, respectively, for 14 days. Growth of vegetative cells and spores of B. cereus after an initial period of inhibition is attributed to loss of activity of nisin. One of two test strains produced diarrheal enterotoxin in gravy stored at 8 or 15 degrees C within 9 or 3 days, respectively. Enterotoxin production was inhibited in gravy supplemented with 1 microgram of nisin/ml and stored at 8 degrees C for 14 days; 5 micrograms of nisin/ml was required for inhibition at 15 degrees C. Enterotoxin was not detected in gravy in which less than 5.85 log10 CFU of B. cereus/ml had grown. Results indicate that as little as 1 microgram of nisin/ml may be effective in inhibiting or retarding growth of and diarrheal enterotoxin production by vegetative cells and spores of psychrotrophic B. cereus in beef gravy at 8 degrees C, a temperature exceeding that recommended for storage or for most unpasteurized, ready-to-serve meat products.

Effects of nisin and temperature on survival, growth, and enterotoxin production characteristics of psychrotrophic Bacillus cereus in beef gravy.

PubMed Central

Beuchat, L R; Clavero, M R; Jaquette, C B

1997-01-01

The presence of psychrotrophic enterotoxigenic Bacillus cereus in ready-to-serve meats and meat products that have not been subjected to sterilization treatment is a public health concern. A study was undertaken to determine the survival, growth, and diarrheal enterotoxin production characteristics of four strains of psychrotrophic B. cereus in brain heart infusion (BHI) broth and beef gravy as affected by temperature and supplementation with nisin. A portion of unheated vegetative cells from 24-h BHI broth cultures was sensitive to nisin as evidenced by an inability to form colonies on BHI agar containing 10 micrograms of nisin/ml. Heat-stressed cells exhibited increased sensitivity to nisin. At concentrations as low as 1 microgram/ml, nisin was lethal to B. cereus, the effect being more pronounced in BHI broth than in beef gravy. The inhibitory effect of nisin (1 microgram/ml) was greater on vegetative cells than on spores inoculated into beef gravy and was more pronounced at 8 degrees C than at 15 degrees C. Nisin, at a concentration of 5 or 50 micrograms/ml, inhibited growth in gravy inoculated with vegetative cells and stored at 8 or 15 degrees C, respectively, for 14 days. Growth of vegetative cells and spores of B. cereus after an initial period of inhibition is attributed to loss of activity of nisin. One of two test strains produced diarrheal enterotoxin in gravy stored at 8 or 15 degrees C within 9 or 3 days, respectively. Enterotoxin production was inhibited in gravy supplemented with 1 microgram of nisin/ml and stored at 8 degrees C for 14 days; 5 micrograms of nisin/ml was required for inhibition at 15 degrees C. Enterotoxin was not detected in gravy in which less than 5.85 log10 CFU of B. cereus/ml had grown. Results indicate that as little as 1 microgram of nisin/ml may be effective in inhibiting or retarding growth of and diarrheal enterotoxin production by vegetative cells and spores of psychrotrophic B. cereus in beef gravy at 8 degrees C, a temperature exceeding that recommended for storage or for most unpasteurized, ready-to-serve meat products. PMID:9143127

Determination of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in human plasma by solid-phase extraction and column-switching high-performance liquid chromatography with ultraviolet detection.

PubMed

Ono, I; Matsuda, K; Kanno, S

1996-04-12

A column-switching high-performance liquid chromatography method with ultraviolet detection at 210 nm has been developed for the determination of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (AY4166, I) in human plasma. Plasma samples were prepared by solid-phase extraction with Sep-Pak Light tC18, followed by HPLC. The calibration graph for I was linear in the range 0.1-20 micrograms/ml. The limit of quantitation of I, in plasma, was 0.05 microgram/ml. The recovery of spiked I (0.5 microgram/ml) to drug-free plasma was over 92% and the relative standard deviation of spiked I (0.5 microgram/ml) compared to drug-free plasma was 4.3% (n = 8).

Estimation of protective levels of anti-O-specific lipopolysaccharide immunoglobulin G antibody against experimental Escherichia coli infection.

PubMed

Schiff, D E; Wass, C A; Cryz, S J; Cross, A S; Kim, K S

1993-03-01

Serum obtained after immunization with an O18 polysaccharide-toxin A conjugate vaccine was evaluated for the estimation of protective levels of anti-O-specific lipopolysaccharide (LPS) immunoglobulin G (IgG) antibody against bacteremia and death caused by a homologous serotype of Escherichia coli K1 strains. Passive transfer of rabbit serum conferred significant protection from a lethal E. coli infection in a neonatal rat model. The overall incidence of bacteremia and mortality was 4% in rat pups receiving undiluted postvaccination serum, while that in control animals was 100% (P < 0.001). The overall incidences of bacteremia were 5 and 72% for animals with serum anti-O18 LPS IgG concentrations of > 1.0 and < 1.0 microgram/ml, respectively, while the overall incidences of mortality for animals with serum anti-O18 LPS IgG levels of > 1.0 and < 1.0 microgram/ml were 0 and 72%, respectively (P < 0.001). Protection against E. coli infection was also demonstrated with human anti-O18 polysaccharide IgG. None of the animals with human anti-O18 LPS IgG levels of > 1 microgram/ml had bacteremia after bacterial challenge, whereas all animals with bacteremia at 18 h had levels of < 1 microgram/ml. These findings suggest that serum anti-O18 LPS IgG concentrations of > 1.0 microgram/ml may provide protection against bacteremia and death caused by a homologous E. coli K1 infection.

[Microbiological and pharmacokinetic studies on flomoxef in ophthalmologic field].

PubMed

Ooishi, M; Sakaue, F; Oomomo, A; Tazawa, H

1989-05-01

Microbiological and pharmacokinetic studies were carried out on flomoxef (FMOX, 6315-S), a new oxacephem parenteral antibiotic, in the ophthalmologic field. The results obtained are summarized as follows. FMOX has a broad antimicrobial activity spectrum against Gram-positive and Gram-negative bacteria. The MIC distribution against Staphylococcus aureus isolated from clinical cases was less than or equal to 0.20 - greater than or equal to 100 micrograms/ml with the peak value of 0.39 micrograms/ml. Concentrations of FMOX in aqueous humor and ocular tissues were determined after intravenous injection of 50 mg/kg to rabbits. FMOX showed a peak level of 2.2 micrograms/ml in the aqueous humor at 1/2 hour after administration with the ratio to serum level of 3.4%. Levels of FMOX in external and internal ocular tissues were 12.7 - 76.5 micrograms/g, less than 0.8 - 34.4 micrograms/g (ml) at 1/2 hour after administration, respectively. From these results, we concluded that FMOX may be expected to be a useful and valuable agent against infections in the ophthalmologic field.

The Cytotoxicity of Dacarbazine Potentiated by Sea Cucumber Saponin in Resistant B16F10 Melanoma Cells through Apoptosis Induction.

PubMed

Baharara, Javad; Amini, Elaheh; Nikdel, Najme; Salek-Abdollahi, Farzaneh

2016-01-01

Malignant melanoma is a highly aggressive malignant melanocytic neoplasm which resists against the most conventional therapies. Sea cucumber as one of marine organisms contains bioactive compounds such as polysaccharide, terpenoid and other metabolites which have anti-cancer, anti-tumor, anti-inflammatory and antioxidant properties. The present study was designed to investigate the anticancer potential of saponin extracted from sea cucumber Holothuria leucospilata alone and in combination with dacarbazine on B16F10 melanoma cell line. The B16F10 cell line was treated with different concentrations of saponin (0, 4, 8, 12, 16, 20 μg/ml), dacarbazine (0, 1200, 1400, 1600, 18000, 1200, 1400, 1600, 2000 μg/ml) and co-administration of saponin-dacarbazine (1200 da+8 sp, 1200 da+4 sp) for 24 and 48 hr and the cytotoxic effect was examined by MTT, DAPI, acridine orange/propodium iodide, flow cytometry and caspase colorimetric assay. The results exhibited that sea cucumber saponin, dacarbazine, and co-administration of saponin-dacarbazine inhibited the proliferation of melanoma cells in a dose and time dependent manner with IC50 values of 10, 1400 and 4+1200 μg/ml, respectively. Morphological observation of DAPI and acridine orange/propodium iodide staining documented typical characteristics of apoptotic cell death. Flow cytometry assay indicated accumulation of IC50 treated cells in sub-G1 peak. Additionally, saponin extracted induced intrinsic apoptosis via up-regulation of caspase-3 and caspase-9. These results revealed that the saponin extracted from sea cucumber as a natural anti-cancer compound may be a new treatment modality for metastatic melanoma and the application of sea cucumber saponin in combination with dacarbazine demonstrated the strongest anti-cancer activity as compared with the drug alone.

[Fundamental studies on legionellosis--the growth with in Acanthamoeba sp. and antibiotics susceptibility of Legionella spp. isolated from soil samples in Japan].

PubMed

Furuhata, Katsunori; Miyamoto, Hiroshi; Hara, Motonobu; Fukuyama, Masafumi

2003-02-01

As part of an epidemiological study of legionellosis, we investigated the growth within Acanthamoeba sp. and antibiotic susceptibility of 62 strains of Legionella spp. isolated from surface soils nationwide in 2001. 1) All strains tested grew in Acanthamoeba sp., suggesting that the strains were pathogenic. The minimum bacterial number required for the growth in the amoeba was 10(3)-10(8) CFU/ml and there were differences between the strains. 2) Susceptibility to 10 drugs was investigated using the Etest. The MIC90 values of imipenem, as a beta-lactam, and rifampicin, as an antitubercular agent, were 0.047 microgram/ml and 0.064 microgram/ml, respectively, showing high sensitivity. In contrast, sensitivity to minocycline, as a tetracycline, and piperacillin, as a beta-lactam, was low and the MIC90 values were 12 micrograms/ml and 16 micrograms/ml, respectively. Sensitivity to minocycline was particularly low, with a MIC value of 32 micrograms/ml, in two strains. The above findings suggested that all soil-derived strains were pathogenic, and susceptibility of the strains tended to be slightly lower than that of clinical isolates.

In vitro susceptibility of Trichophyton rubrum isolates to griseofulvin and tioconazole. Induction and isolation of a resistant mutant to both antimycotic drugs. Mutant of Trichophyton rubrum resistant to griseofulvin and tioconazole.

PubMed

Fachin, A L; Maffei, C M; Martinez-Rossi, N M

1996-01-01

The in vitro susceptibility of three clinical Trichophyton rubrum isolates to griseofulvin and tioconazole, determined by the minimal inhibitory concentration (MIC), was 2 and 0.5 to 1.0 micrograms/ml, respectively. One mutant (gril) obtained after mutagenic treatment of one of these isolates was selected and showed simultaneous resistance to griseofulvin (MIC > 2000 micrograms/ml) and tioconazole (MIC = 1.0 microgram/ml). The clinical importance and the possibility of a multidrug resistance (MDR)-type mechanism being involved in this event is discussed.

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

PubMed Central

Fantin, B; Leclercq, R; Arthur, M; Duval, J; Carbon, C

1991-01-01

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin. PMID:1834013

In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens.

PubMed

Pijpers, A; Van Klingeren, B; Schoevers, E J; Verheijden, J H; Van Miert, A S

1989-09-01

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline-susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n = 17) 0.25-0.5 micrograms/ml; B. bronchiseptica (n = 20) 0.25-1.0 micrograms/ml; H. pleuropneumoniae (n = 20) 0.25-0.5 micrograms/ml; S. suis Type 2 (n = 20) 0.06-0.25 micrograms/ml. For 19 oxytetracycline-resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 micrograms/ml for oxytetracycline to 0.5 micrograms/ml for minocycline. Strikingly, minocycline showed no cross-resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampicillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lincomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.

Kinetics of absorption and elimination of ofloxacin in humans after oral and rectal administrations.

PubMed

Eboka, C J; Okor, R S; Akerele, J O; Aigbavboa, S O

1997-06-01

Ofloxacin pharmacokinetics have been studied in four healthy subjects after a single oral or rectal dose, each of 200 mg. For the oral dose tmax was about 2 h, Cmax 1.96 +/- 0.56 micrograms/ml and AUC1-15 15.22 micrograms/ml.h. Two-phase elimination pharmacol kinetics were observed for the oral dose, t1/2 for the rapid elimination phase was 3.3 h and for the slow phase 10 h. With the rectal dose tmax was 6 h, Cmax 0.71 +/- 0.44 microgram/ml and AUC0-15 7.58 micrograms/ml.h. The relative rectal bioavailability (AUC rectal/AUC oral) was 49.8%. Elimination rate of the rectal dose was generally slow (t1/2 = 9 h), an observation attributable to the sustained-release effect of the rectal suppository base, PEG 6000. The indication is that the rectal formulation cannot be substituted totally for the oral without first increasing the rectal dose; the 200 mg suppository can however be employed as a follow-up therapy to the oral dose in certain situations.

Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents.

PubMed Central

Vildé, J L; Dournon, E; Rajagopalan, P

1986-01-01

The activity of serial concentrations of different antimicrobial agents on the multiplication of Legionella pneumophila within human monocyte-derived macrophages was studied. The results led to the definition of a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). According to the MIECs, the antimicrobial agents tested were classified in three groups: very active (MIEC less than or equal to 0.06 microgram/ml), such as erythromycin, rifampin, and pefloxacin; active (1 microgram/ml greater than or equal to MIEC greater than or equal to 0.1 microgram/ml), such as sulfamethoxazole-trimethoprim or doxycycline; and ineffective, such as cefoxitin, which was not active within macrophages at as high as 64 micrograms/ml despite a low MIC (0.2 microgram/ml) on bacterial charcoal-yeast extract agar. The activity of netilmicin was difficult to assess because of its effect on extracellular legionellae. Combinations of erythromycin with rifampin and pefloxacin with erythromycin, rifampin, doxycycline, or netilmicin showed an additive effect and no antagonism. These results obtained in a cellular model are in agreement with the efficacy of antimicrobial agents in experimental infections and in Legionnaires disease. They sustain clinical interest in the new quinolones, such as pefloxacin, and in combinations of antimicrobial agents for the treatment of Legionnaires disease. PMID:3492176

Haemolytic and Antimicrobial Activites of Saponin-Rich Extracts from Guar Meal

USDA-ARS?s Scientific Manuscript database

Saponin-rich GM extract was prepared by refluxing 25 g of GM with 250 ml of EtOH/H2O (1:1, v/v) for 3 h then filtering and distilling EtOH at 50oC. The refluxed extract was partitioned with equal volume of BuOH obtaining crude saponin-rich GM extract with 4.8 ± 0.6% DM of GM that was purified by RP...

Acetanilide and paracetamol pharmacokinetics before and during phenytoin administration: genetic control of induction?

PubMed Central

Cunningham, J L; Evans, D A

1981-01-01

1 Steady state plasma concentrations (SSPCs) of acetanilide (AA) and its metabolite, paracetamol (PL), were studied in 27 healthy volunteer subjects before and at the end of an 11-day exposure to phenytoin (DPH). Plasma concentrations of DPH were estimated. Plasma concentrations of DPH varied from 5.1 to 20.4 microgram ml-1 (mean +/- s.e.mean 12.2 +/- 0.9). 2 The SSPC of AA before exposure to DPH varied from 0.06 to 0.67 microgram ml-1 (mean +/- s.e.mean 0.24 +/- 0.02), and following exposure from 0.03 to 0.47 microgram ml-1 (mean +/- s.e.mean 0.15 +/- 0.02). 3 The SSPC of PL before exposure to DPH varied from 1.2 to 4.4 microgram ml-1 (mean +/- s.e.mean 2.7 +/- 0.13), and following exposure from 1.1 to 3.8 microgram ml-1 (mean +/- s.e.mean 2.2 +/- 0.13). 4 SSPCs of AA and of PL decreased significantly during DPH administration (P less than 0.01 for AA, P less than 0.001 for PL). 5 Correlations were observed between the SSPCs of the drugs measured, suggesting a common influence on their kinetics. 6 Similarity was observed between the changes in plasma levels of AA and PL following DPH ingestion. There was, however, wide inter-subject variability in this regard. In some subjects no change was observed even though they had DPH demonstrable in their plasma. Consequently it may be speculated that the effects of DPH may be under genetic control. PMID:7272175

Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

PubMed Central

Landoy, Z; West, T E; Vladutiu, A O; Fitzpatrick, J E

1985-01-01

A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, P<0.001). The Cordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories. PMID:3897269

Determination of apalcillin and its metabolites in human body fluids by high-pressure liquid chromatography.

PubMed Central

Borner, K; Lode, H; Elvers, A

1982-01-01

We describe two methods for the quantitative analysis of apalcillin and its metabolites in serum and urine by reverse-phase high-pressure liquid chromatography (HPLC), a fast isocratic method for the parent drug, and a gradient method that allows the simultaneous assay of two metabolites. Serum was deproteinized with acetonitrile, and urine was diluted with buffer solution. The detection limit was about 0.5 micrograms/ml at a detection wavelength of 254 nm and 1.5 micrograms/ml at 310 nm. Within-batch precision (coefficient of variation) varied from 10.2 to 1.1% for concentrations of 7.8 and 185.3 micrograms/ml of serum, respectively. Recovery rates of 95.1 and 97.7% were found in spiked sera. Results obtained by HPLC correlated well with those from a standard microbiological assay (agar diffusion test); the resulting bivariate regression equation for serum was y-bioassay = 2.5 micrograms/ml + 0.992 X xHPLC, and that for urine was ybioassay = 12.0 micrograms/ml + 1.009 X xHPLC. At a detection wavelength of 315 nm, no interferences were observed in 10 healthy volunteers. Healthy subjects who were given 2 g of apalcillin intravenously excreted 18% of the parent drug within 24 h in the urine. Two inactive compounds were furthermore identified in urine as the isomeric forms of the penicilloic acids. Their excretion within 24 h amounted to 6.9 and 11.2% of the dose. PMID:6818901

The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non-pregnant women.

PubMed Central

Heikkilä, A; Pyykkö, K; Erkkola, R; Iisalo, E

1992-01-01

1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam (n = 12) were studied in pregnant (n = 27) and non-pregnant (n = 12) subjects. 2. In early pregnancy (9-14 weeks of gestation) the mean peak plasma drug concentration (Cmax = 19 +/- 9 micrograms ml-1) after an intravenous injection of 200 mg mecillinam was significantly lower (P less than 0.05) and the volume of distribution (V = 49 +/- 20.1) significantly larger (P less than 0.05) than in non-pregnant subjects (Cmax = 35 +/- 18 micrograms ml-1, V = 29 +/- 12.1). In late pregnancy (39-40 weeks of gestation) the plasma mean peak concentration (Cmax = (29 +/- 14 micrograms ml-1) after parenteral administration of 200 mg mecillinam was slightly lower and the volume of distribution (V = 65 +/- 29.1, V = 0.9 +/- 0.4 l kg-1) significantly larger than that in non-pregnant subjects (V = 0.4 +/- 0.3 l kg-1). Also after oral administration of 200 mg pivmecillinam, equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant subjects (Cmax = 1.8 +/- 1.2 micrograms ml-1) was slightly lower than that in non-pregnant subjects (Cmax = 1.7 +/- 1.2 micrograms ml-1). 3. The mean half-life of elimination after parenteral administration of mecillinam was significantly longer during both early (t1/2,Z = 133 +/- 38 min, P less than 0.05) and late pregnancy (t1/2,Z = 107 +/- 41 min, P less than 0.05) as compared with the non-pregnant state (t1/2,Z = 75 +/- 21 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1389936

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922.

PubMed Central

Furneri, P M; Bisignano, G; Cerniglia, G; Nicoletti, G; Cesana, M; Tempera, G

1994-01-01

The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90% of isolates tested [MIC90s], 0.5 to 4 micrograms/ml. Ofloxacin had the lowest MIC90s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 micrograms/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 micrograms/ml). PMID:7872762

Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.

PubMed Central

Horwitz, M A; Silverstein, S C

1983-01-01

We have previously reported that virulent egg yolk-grown Legionella pneumophila, Philadelphia 1 strain, multiplies intracellularly in human blood monocytes and only intracellularly under tissue culture conditions. In this paper, we have investigated the effect of erythromycin and rifampin on L. pneumophila-monocyte interaction in vitro; erythromycin and rifampin are currently the drugs of choice for the treatment of Legionnaires' disease. The intracellular multiplication of L. pneumophila is inhibited by erythromycin and rifampin, as measured by colony-forming units, whether the antibiotics are added just before or just after infection of monocytes with L. pneumophila, or 2 d after infection when L. pneumophila is in the logarithmic phase of growth in monocytes. Intracellular multiplication of L. pneumophila is inhibited by 1.25 microgram/ml but not less than or equal to 0.125 microgram/ml erythromycin and 0.01 microgram/ml but not less than or equal to 0.001 microgram/ml rifampin. These concentrations of antibiotics are comparable to those that inhibit extracellular multiplication of L. pneumophila under cell-free conditions in artificial medium; the minimal inhibitory concentration is 0.37 microgram/ml for erythromycin and 0.002 microgram/ml for rifampin. Multiplication of L. pneumophila in the logarithmic phase of growth in monocytes is inhibited within 1 h of the addition of antibiotics. Intracellular bacteria inhibited from multiplying by antibiotics are not killed. By electron microscopy, the bacteria appear intact within membrane-bound vacuoles, studded with ribosomelike structures. L. pneumophila multiplying extracellularly on artificial medium is killed readily by relatively low concentrations of erythromycin and rifampin; the minimal bactericidal concentration is 1 microgram/ml for erythromycin and 0.009 microgram/ml for rifampin. In contrast, L. pneumophila multiplying intracellularly is resistant to killing by these concentrations of erythromycin and rifampin or by concentrations equal to or greater than peak serum levels in humans. Extracellular L. pneumophila in stationary phase is also resistant to killing by erythromycin and rifampin. These findings, taken together with our previous work, indicate that, in vivo, L. pneumophila is resistant to killing by erythromycin and rifampin. Inhibition of L. pneumophila multiplication in monocytes by antibiotics is reversible; when the antibiotics are removed from infected monocyte cultures after 2 d, L. pneumophila resumes multiplication. This study indicates that patients with Legionnaires' disease under treatment with erythromycin and rifampin require host defenses to eliminate L. pneumophila, and that inadequate host defenses may result in relapse after cessation of therapy. PMID:6848556

Vitamin A (retinol and retinyl esters), alpha-tocopherol and lipid levels in plasma of captive wild mammals and birds.

PubMed

Schweigert, F J; Uehlein-Harrell, S; von Hegel, G; Wiesner, H

1991-02-01

Vitamin A (retinol and retinyl esters), vitamin E and lipids were determined in a wide variety of wild mammals and birds held in captivity. In mammals plasma levels of vitamin A were generally below 500 ng/ml and those of vitamin E were highly variable (0.1-2 micrograms/ml). In primates, vitamin E levels were 3 to 8 micrograms/ml. Whereas in Marsupialia, Chiroptera, primates, Rodentia, Proboscidea, Sirenia, Perissodactyla and Artiodactyla only retinol was found, retinyl esters (basically retinol palmitate/oleate) represented 10 to 50% of the total plasma vitamin A in some birds of the order Ciconiiformes and Falconiformes. Retinol levels in birds were higher compared to mammals (500-2,000 ng/ml). The same was true for lipids as well as for vitamin E levels (1-26 micrograms/ml) in the plasma of birds.

Comparative activity of several beta-lactam antibiotics against anaerobes determined by two methods.

PubMed

Zabransky, R J; Birk, R J

1987-01-01

The susceptibility of 120 strains of several species of anaerobes to a number of second and third generation beta-lactam antibiotics was determined by the National Committee for Clinical Laboratory Standards reference agar dilution and microdilution methods. The antibiotics tested were cefoperazone, cefotaxime, cefotetan, ceftizoxime, cefoxitin, and imipenem. The MIC50s ranged from 0.125 to 16 micrograms/ml. The MIC90s were lowest with imipenem at 0.5 micrograms/ml, followed by cefoxitin at 32 micrograms/ml; they were highest with cefotetan at 128 micrograms/ml and were 64 micrograms/ml with the others. In vitro drug activity varied with the antibiotic, the organism, the method used, and the breakpoint selected. Rates of resistance varied considerably between the taxonomic groups of organisms tested and also among species within a group. Overall, reproducibility with the agar dilution method ranged from 44% to 85%; testing with ceftizoxime was the least reproducible. Microdilution results agreed within +/- 1 dilution of the agar dilution mode 79% to 95% of the time, with some variation between drugs and organisms tested. Because there were distinct differences in the activity of some drugs against certain species, no antibiotic can substitute for others in in vitro testing.

Enoxacin decreases the clearance of theophylline in man.

PubMed Central

Wijnands, W J; Vree, T B; Van Herwaarden, C L

1985-01-01

In patients treated concurrently with theophylline and enoxacin, a new broad-spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/- s.d. theophylline concentrations increased from 8.5 +/- 2.8 micrograms ml-1 prior to enoxacin to a maximum of 21.7 +/- 7.8 micrograms ml-1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/- 2.4 micrograms ml-1 prior to enoxacin treatment to 15.0 +/- 5.1 micrograms ml-1 at day 3 of coadministration (P less than 0.005). Plasma protein-binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended. PMID:3867394

Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

PubMed

Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M

1997-07-01

Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

[Studies on the extraction and purification of total saponins from Parched Semen Ziziphi Spinosae].

PubMed

Wu, Yulan; Ding, Anwei; Bao, Beihua

2005-03-01

To study the extraction and purification process of the total saponin from Parched Semen Ziziphi Spinosae with ethanol and macroporous resin. The total saponins were extracted with ethanol and purified with macroporous resin by orthogonal design, taking content and purity of jujuboside A as guideline. The optimum extraction condition was adding 6 times amount of 80% ethanol and refluxing 3 times, for 30 minutes each time. The purification process with macroporous resin HPD-100 was using 0.5% NaOH (150ml), 30% ethanol (150ml) to wash out impurity, and 70% ethanol 50 ml to wash out saponin. The purity of jujuboside A was up to 17.9% and the eluted ratio 72.8%.

Evaluation of the effect of antiarthritic drugs on the secretion of proteoglycans by lapine chondrocytes using a novel assay procedure.

PubMed Central

Collier, S; Ghosh, P

1989-01-01

A new method is described for separating free 35SO4-- from 35SO4 labelled proteoglycans synthesised by rabbit articular chondrocytes cultured in the presence of excess 35SO4--. The procedure uses the low solubility product of barium sulphate to remove, by precipitation, free 35SO4-- from culture medium. Optimum recovery of 35SO4 labelled proteoglycans was achieved after papain digestion to release 35SO4-glycosaminoglycans, and addition of chondroitin sulphate before the precipitation step. Using this assay, we studied the effect of six drugs-indomethacin, diclofenac, sodium pentosan polysulphate, glycosaminoglycan polysulphate ester, tiaprofenic acid, and ketoprofen-on the secretion into the medium of labelled proteoglycans by lapine chondrocytes. The six drugs were tested at 0.1, 1, 10, 50, and 100 micrograms/ml over four consecutive 48 hour culture periods. A consistent concentration-response pattern was found for the four non-steroidal anti-inflammatory drugs (NSAIDs) studied. Generally they inhibited proteoglycan secretion at 50 and 100 micrograms/ml but had no effect at lower concentrations. Inhibition of secretion was strongest with indomethacin and diclofenac at 50 and 100 micrograms/ml. In contrast with the NSAIDs studied, the two sulphated polysaccharides (sodium pentosan polysulphate and glycosaminoglycan polysulphate ester) at low concentrations increased proteoglycan secretion by chondrocytes, with maximal stimulation occurring at 1 microgram/ml. Sodium pentosan polysulphate, but not glycosaminoglycan polysulphate ester, showed inhibitory activity at 50 and 100 micrograms/ml. PMID:2471470

The Cytotoxicity of Dacarbazine Potentiated by Sea Cucumber Saponin in Resistant B16F10 Melanoma Cells through Apoptosis Induction

PubMed Central

Baharara, Javad; Amini, Elaheh; Nikdel, Najme; Salek-Abdollahi, Farzaneh

2016-01-01

Background: Malignant melanoma is a highly aggressive malignant melanocytic neoplasm which resists against the most conventional therapies. Sea cucumber as one of marine organisms contains bioactive compounds such as polysaccharide, terpenoid and other metabolites which have anti-cancer, anti-tumor, anti-inflammatory and antioxidant properties. The present study was designed to investigate the anticancer potential of saponin extracted from sea cucumber Holothuria leucospilata alone and in combination with dacarbazine on B16F10 melanoma cell line. Methods: The B16F10 cell line was treated with different concentrations of saponin (0, 4, 8, 12, 16, 20 μg/ml), dacarbazine (0, 1200, 1400, 1600, 18000, 1200, 1400, 1600, 2000 μg/ml) and co-administration of saponin-dacarbazine (1200 da+8 sp, 1200 da+4 sp) for 24 and 48 hr and the cytotoxic effect was examined by MTT, DAPI, acridine orange/propodium iodide, flow cytometry and caspase colorimetric assay. Results: The results exhibited that sea cucumber saponin, dacarbazine, and co-administration of saponin-dacarbazine inhibited the proliferation of melanoma cells in a dose and time dependent manner with IC50 values of 10, 1400 and 4+1200 μg/ml, respectively. Morphological observation of DAPI and acridine orange/propodium iodide staining documented typical characteristics of apoptotic cell death. Flow cytometry assay indicated accumulation of IC50 treated cells in sub-G1 peak. Additionally, saponin extracted induced intrinsic apoptosis via up-regulation of caspase-3 and caspase-9. Conclusion: These results revealed that the saponin extracted from sea cucumber as a natural anti-cancer compound may be a new treatment modality for metastatic melanoma and the application of sea cucumber saponin in combination with dacarbazine demonstrated the strongest anti-cancer activity as compared with the drug alone. PMID:27563423

Quantitative measurement of human thyroglobulin-specific antibodies by use of a sensitive enzyme-linked immunoassay.

PubMed

Kuppers, R C; Outschoorn, I M; Hamilton, R G; Burek, C L; Rose, N R

1993-04-01

A quantitative enzyme-linked immunoassay that measures in absolute terms the subclass concentration of human thyroglobulin (huTg)-specific IgG autoantibody was developed. Unique to this study was the use of an affinity-purified anti-huTg standard with a known concentration of the four IgG subclasses. The sensitivity of the ELISA assay was 1-5 ng/ml depending on the IgG subclass being measured. We examined 22 sera of patients with autoimmune thyroid disease. The total huTg-specific antibody concentrations in serum ranged from 0 to nearly 3000 micrograms/ml of IgG. The IgG subclass distribution in individuals with low huTg-specific IgG (< 10 micrograms/ml) was primarily IgG1 and IgG3 Ab. Patients with intermediate levels of huTg IgG (10-600 micrograms/ml) expressed all four subclasses; however, no particular subclass was dominant. Individuals with > 1000 micrograms/ml also showed huTg-Ab in all four subclasses, however, IgG1 and IgG2 were dominant. All four IgG subclasses were used in the response to huTg, although the pattern of usage varied between individuals. There was no dominant subclass usage seen in this patient population.

Prevalence and determinants of lead intoxication in Mexican children of low socioeconomic status.

PubMed Central

López-Carrillo, L; Torres-Sánchez, L; Garrido, F; Papaqui-Hernández, J; Palazuelos-Rendón, E; López-Cervantes, M

1996-01-01

This paper reports on the prevalence of lead poisoning in children between 1 and 5 years of age living in a marginal area to the north of Mexico City and also includes an evaluation of sources of exposure to this metal in the same area. The results show that 67.5% of the children studied have blood lead (PbB) levels > or = 10 micrograms/100 ml. Twenty-one percent of these children (1987) had PbB levels that required medical evaluation (> or = 20 micrograms/100 ml- < or = 40 micrograms/100 ml), and 112 children needed medical treatment (PbB > or = 40 micrograms/100 ml). In addition, the study found that the probability of higher blood lead levels (> or = 20 micrograms/dl) corresponds to children whose mothers use lead-glazed pottery dishes (OR = 2.80; CI 95%, 1.55-5.07) and to children who habitually bite colored pencils (OR = 2.05; CI 95%, 1.13-3.71) compared, respectively, with children whose mothers do not use that type of dishes and children who do not bite pencils. Our results provide baseline information for estimating the impact and costs of population-based interventions aimed at these populations and also confirm the need to strengthen health education programs to promote the reduction of lead exposure in the general population. PMID:8959410

Oxyrase, a method which avoids CO2 in the incubation atmosphere for anaerobic susceptibility testing of antibiotics affected by CO2.

PubMed

Spangler, S K; Appelbaum, P C

1993-02-01

The Oxyrase agar dilution method, with exclusion of CO2 from the environment, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibility of 51 gram-negative and 43 gram-positive anaerobes to azithromycin and erythromycin. With the Oxyrase method, anaerobiosis was achieved by incorporation of the O2-binding enzyme Oxyrase in addition to susceptibility test medium, antibiotic, and enzyme substrates into the upper level of a biplate. Plates were covered with a Brewer lid and incubated in ambient air. With azithromycin, Oxyrase yielded an MIC for 50% of strains tested (MIC50) and MIC90 of 2.0 and 8.0 micrograms/ml, compared to 8.0 and > 32.0 micrograms/ml in standard anaerobic conditions. At a breakpoint of 8.0 micrograms/ml, 90.4% of strains were susceptible to azithromycin with Oxyrase, compared to 53.2% in the chamber. The corresponding erythromycin MIC50 and MIC90 were 1.0 and 8.0 micrograms/ml with Oxyrase, compared to 4.0 and > 32.0 micrograms/ml by the reference method, with 89.3% of strains susceptible at a breakpoint of 4 micrograms/ml with Oxyrase, compared to 60.6% in CO2. Exclusion of CO2 from the anaerobic atmosphere when testing for susceptibility to azalides and macrolides yielded lower MICs, which may lead to a reconsideration of the role played by these compounds in treatment of infections caused by these strains.

Comparative in vitro activity of CGP 31608, a new penem antibiotic.

PubMed Central

Eliopoulos, G M; Wennersten, C; Reiszner, E; Moellering, R C

1987-01-01

The in vitro activity of a new penem antimicrobial agent, CGP 31608, was compared with those of imipenem, SCH 34343, and several other antimicrobial agents against approximately 600 bacterial isolates. CGP 31608 was active against gram-positive organisms, including methicillin-susceptible Staphylococcus aureus (MIC for 90% of the isolates [MIC90], 0.25 microgram/ml) and penicillin-susceptible streptococci (MIC90s, less than or equal to 2 micrograms/ml). Penicillin-resistant streptococci (including enterococci) and methicillin-resistant S. aureus were more resistant to the penem. Activities of CGP 31608 against members of the family Enterobacteriaceae were remarkably uniform, with MIC90s of 8 to 16 micrograms/ml. CGP 31608 was at least as active as imipenem and ceftazidime and more active than piperacillin against Pseudomonas aeruginosa. Drug activity was not influenced by the presence of any of 10 plasmid-mediated beta-lactamases. Against strains of Serratia marcescens, Enterobacter cloacae, and P. aeruginosa with derepressible chromosomally mediated beta-lactamases, the presence of cefoxitin did not induce increased resistance to CGP 31608. The new drug was also active against anaerobes (MIC90s, 0.25 to 8 micrograms/ml), Haemophilus influenzae (MIC90s, 0.5 to 1.0 micrograms/ml), and Legionella spp. (MIC90, 2 micrograms/ml). CGP 31608 showed an antibacterial spectrum similar to those of imipenem and SCH 34343 (except that the latter is not active against P. aeruginosa) but was generally less potent than these drugs. However, CGP 31608 demonstrated more activity (MIC90) than imipenem against P. aeruginosa, Pseudomonas cepacia, and methicillin-resistant Staphylococcus epidermidis and S. aureus. PMID:3498437

In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin with a broad antibacterial spectrum.

PubMed Central

Hata, K; Otsuki, M; Nishino, T

1992-01-01

E1077 is a new injectable cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria, including staphylococci and Pseudomonas aeruginosa. The in vitro activities of E1077 against clinical isolates of methicillin-susceptible Staphylococcus aureus (MIC of E1077 for 90% of the strains tested [MIC90], 0.78 microgram/ml) and methicillin-resistant S. aureus (MIC90, 50 micrograms/ml) were similar to those of cefpirome and flomoxef. Against Enterococcus faecalis (MIC90, 6.25 micrograms/ml), E1077 was the most active of the drugs tested and four times more active than cefpirome. The MIC90S of E1077 for streptococci, Haemophilus influenzae, and Neisseria gonorrhoeae ranged from 0.05 to 0.78 microgram/ml; E1077 was similar in activity to cefpirome. E1077 inhibited 90% of most species of the family Enterobacteriaceae at concentrations of less than or equal to 1.56 micrograms/ml, with the exception of Serratia marcescens and Proteus vulgaris (12.5 micrograms/ml). The activity of E1077 against P. aeruginosa (MIC90, 6.25 micrograms/ml) was comparable to that of ceftazidime. In vivo activity was evaluated with systemic infections in mice. E1077 showed a protective effect against systemic infections by gram-positive or gram-negative bacteria, as reflected by its in vitro activity. The protective effects of E1077 were higher than those of cefpirome against S. aureus and P. aeruginosa infections and similar to those of cefpirome against other bacterial infections. Morphological studies using differential interference and phase-contrast microscopy showed that low concentrations of E1077 caused swelling of S. aureus and spheroplast and bulge formation in P. aeruginosa. In general, the antibacterial profile of E1077 is similar to that of cefpirome. Images PMID:1416879

Cytotoxic effects of cuphiin D1 on the growth of human cervical carcinoma and normal cells.

PubMed

Wang, Ching-Chiung; Chen, Lih-Geeng; Yang, Ling-Ling

2002-01-01

Cuphiin D1 (CD1), macrocyclic hydrolyzable tannin isolated from Cuphea hyssopifolia, has been shown to exert an antitumor effect both in vitro and in vivo. Furthermore, CD1 significantly inhibited the growth of the human cervical carcinoma, i.e. HeLa, cells and showed less cytotoxicity to normal primary-cultured cervical fibroblasts. In this study, we explored the cytotoxic mechanism of CD1 on HeLa cells. The cytotoxic effects of CD1 showed dose-dependency at 3.15-100 micrograms/ml on HeLa for 12, 24, 48 and 72 hours and with an IC50 value at 14.2 micrograms/ml for 48 hours. However, the IC50 value of CD1 in primary-cultured normal cervical fibroblasts was 74.5 micrograms/ml. Therefore, the selectivity shown by CD1 is ascribed to differences in growth speeds between normal and tumor cells. HeLa cells treated with 50 micrograms/ml CD1 for 24 hours exhibited chromatin condensation, indicating the occurrence of apoptosis. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content among HeLa cells. CD1 also caused DNA fragmentation and inhibited Bcl-2, pro-caspase 3, and inactived PARP expression in HeLa cells. These results suggest that the inhibition of Bcl-2 expression in HeLa cells might account for the mechanism of CD1-induced apoptosis.

[Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001].

PubMed

Yamaguchi, Keizo; Ishii, Yoshikazu; Iinuma, Yoshitsugu; Yamanaka, Kiyoharu; Ichiyama, Satoshi; Watanabe, Naoki; Uehara, Nobuyuki; Kaku, Mitsuo; Kurokawa, Yukinori; Hayashi, Mutsumu; Hirakata, Yoichi

2003-12-01

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.

[Pharmacokinetic and clinical studies of ceftizoxime in newborn infants].

PubMed

Sato, H; Nakazawa, S; Narita, A; Nakazawa, S; Matsumoto, K; Suzuki, H; Nakanishi, Y; Chikaoka, H; Kamigaki, M; Niino, K

1988-08-01

Pharmacokinetic and clinical studies of ceftizoxime (CZX) were performed in infants given intravenously. The obtained results are summarized as follows. 1. Serum concentrations of CZX in 2 and 3 day-old mature infants given 20 mg/kg by one shot intravenous injection peaked at 49.0 and 57.9 micrograms/ml in 1 hour and decreased to 14.4 and 24.9 micrograms/ml in 8 hours after dosing, respectively. Half-lives were 3.9 and 5.6 hours, respectively. In 5 day-old or older mature infants, peak serum levels ranged from 20.9 to 38.0 micrograms/ml at 1 hour after the injection. Levels of CZX at 8 hours after injection were 1.31 to 7.32 micrograms/ml. Half-lives were 1.6-3.0 hours in all the infants except one. 2. In a 3 day-old premature infant given the same dose by a bolus intravenous injection, the serum level peaked at 45.7 micrograms/ml in 1 hour after the injection. The level at 8 hours after injection was 15.7 micrograms/ml. The half-life was 4.2 hours. In 5-15 day-old premature infants, half-lives were 2.3-3.1 hours in all the infants except one. 3. Serum concentrations of CZX in 1 and 2 day-old infants given 20 mg/kg by intravenous drip infusion peaked at 49.4 to 115.0 micrograms/ml in 1 hour after dosing. Half-lives were rather long, 4.0 and 5.1 hours, in the 2 infants. 4. Peak serum levels and half-lives tended to be lower and shorter in 5 day-old or older ones than in the 3 day-old or younger infants. 5. No changes in the serum concentration were observed even after dosing with 20 mg/kg of continuous one shot intravenous injection. 6. Urinary recovery rates during the first 8 hours (one is 6 hours, two is 9 hours) after 20 mg/kg intravenous bolus injection of CZX tended to be lower in 3 day-old or younger infants than in 5 day-old or older infants. 7. Eleven infants with various bacterial infections were given CZX by intravenous bolus injection or drip infusion. Dosage of CZX used in the present study were 36-148 mg/kg/day in 2-3 divided doses. Duration of treatment ranged from 3 to 12 days. Clinical efficacy of CZX was excellent or good in all the infants with acute bronchitis, acute pneumonia, suspected sepsis infected in uterine, acute otitis media, cellulitis, meningitis caused by Klebsiella pneumoniae and Escherichia coli, acute urinary tract infection and periproctic abscess except 1 case of acute bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of prometaphase chromosome techniques with emphasis on the role of colcemid.

PubMed

Wiley, J E; Sargent, L M; Inhorn, S L; Meisner, L F

1984-12-01

Six different techniques were evaluated to define better those technical factors that are most critical for obtaining prometaphase cells for banding analysis. Our results demonstrate: colcemid exposures of 30 min or less have no effect on increasing the yield of prometaphase cells, colcemid exposures of greater than 0.1 microgram/ml can be toxic, methotrexate depresses the mitotic index significantly and seems to increase the incidence of prometaphase cells only because it suppresses later forms; and (d) the optimum number of cytogenetically satisfactory prometaphase cells can be obtained with a 4-h exposure to a combination of low concentration actinomycin D (0.5 microgram/ml) and colcemid (0.1 microgram/ml). This technique inhibits chromosome condensation while permitting prometaphase cells to accumulate for 4 h.

Studies on strain sensitivity of Trichomonas vaginalis to metronidazole.

PubMed Central

Meingassner, J G; Havelec, L; Mieth, H

1978-01-01

Ninety-four strains of Trichomonas vaginalis isolated from unselected patients in Vienna during the period from November 1975 to November 1975 were subjected to sensitivity tests against metronidazole in vitro and in vivo. Nearly 90% of the isolates examined showed in vitro growth inhibition at concentrations of 0.4 to 1.6 microgram metronidazole/ml and only about 10% at concentrations of less than 0.4 microgram/ml. All isolates showed some inhibition of growth after incubation for 48 hours with 3.2 microgram metroidazole/ml. Tests on treatment carried out on experimentally infected mice revealed that all strains of T. vaginalis examined were sensitive to metronidazole (MDE: less than 3 x 35 mg/kg peroral). PMID:305807

[Experimental and clinical evaluation of cefotetan in pediatrics].

PubMed

Toyonaga, Y; Kurosu, Y; Sugita, M; Kita, A; Yoshino, N; Kouda, N; Kumagai, K; Horiuchi, K; Hori, M; Takahashi, T

1983-06-01

Preclinical and clinical studies were carried out on cefotetan (CTT), a new synthetic cephamycin antibacterial agent. The results are described below. Antibacterial activity The minimum inhibitory concentrations (MICs) of CTT, CEZ, CTM and CMZ were determined against clinical isolates of S. aureus, E. coli, K. pneumoniae and P. mirabilis. To CTT S. aureus, showed its sensitivity peak (in the graphic plot of the MIC distribution) at a concentration range of 3.13-6.25 micrograms/ml when a 100-fold dilution of the pathological specimen was employed as the inoculum. These results were inferior to those with CEZ and CTM by 2-4 concentration tubes. The CTT results were also about 2 tubes inferior to the results with CMZ, which is a cephamycin antibiotic. On the other hand, CTT was found to show very strong antibacterial activity against Gram-negative rods. For example, the sensitivity peak of E. coli, occurred at an antibiotic concentration of less than or equal to 0.1-0.2 microgram/ml, regardless of whether the inoculum was the undiluted pathological specimen or the 100-fold dilution thereof. Similar results were obtained in relation to the K. pneumoniae strains: at a CTT concentration of less than or equal to 0.1 microgram/ml, suppression of growth was achieved in 74% of the strains when the inocula were the undiluted specimens, and 86% when the inocula were the 100-fold dilutions thereof. In addition, against P. mirabilis, when the inoculum consisted of the undiluted pathological specimen the MIC peak for CTT occurred at a concentration range of 0.39-0.78 microgram/ml, whereas the peak occurred at 0.2-0.39 microgram/ml when the bacterial inoculum was the 100-fold dilution of the collected specimen. In contrast, CTM showed slightly stronger antibacterial activity than CTT in relation to P. mirabilis; that is, its MIC peak occurred at less than or equal to 0.1-0.2 microgram/ml when the inoculum was the undiluted pathological specimen, and at less than or equal to 0.1 microgram/ml when the bacterial inoculum was the 100-fold dilution. Otherwise, against these 3 species of bacteria, CTT yielded results which were clearly superior to those achieved with the other 3 antibiotics. Absorption and excretion CTT was administered to children at a dosage of 10 mg/kg and 20 mg/kg as a one-shot intravenous injection or as a 1-hour intravenous drip infusion. Thereafter, the serum concentration of the antibiotic was monitored and it excretion rate in the urine was also determined.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro activity and human pharmacokinetics of teicoplanin.

PubMed Central

Verbist, L; Tjandramaga, B; Hendrickx, B; Van Hecken, A; Van Melle, P; Verbesselt, R; Verhaegen, J; De Schepper, P J

1984-01-01

The in vitro activity of teicoplanin, a new antibiotic related to vancomycin, was determined against 456 gram-positive cocci. The activity of teicoplanin in comparison with that of vancomycin was similar against staphylococci but 4 to 40 times higher against enterococci and beta-hemolytic and viridans streptococci. The single-dose pharmacokinetics of teicoplanin were studied in six healthy volunteers after administration of 3 and 6 mg/kg intravenously and of 3 mg/kg intramuscularly. The kinetic parameters after both intravenous doses were very similar. The curves for concentration in plasma for the 3- and 6-mg/kg intravenous doses showed a triexponential decline with elimination half-lives of 47.3 and 44.1 h, respectively. The percentages of the doses recovered in urine (0 to 102 h) were 43.2 and 44.1%, respectively. The areas under the plasma curves were dose related: 256.5 and 520.9 micrograms/h per ml, respectively. The bioavailability of teicoplanin after injection of 3 mg/kg intramuscularly was 90%, and the peak level was 7.1 micrograms/ml. The mean levels in plasma 24 h after the 3-mg/kg doses were 2.1 and 2.3 micrograms/ml, respectively, and the mean level in plasma 24 h after the 6-mg/kg intravenous dose was 4.2 micrograms/ml. PMID:6240962

Spectrophotometric determination of phenylephrine HCl and orphenadrine citrate in pure and in dosage forms.

PubMed

Shama, S A

2002-11-07

A simple and rapid spectrophotometric methods have been estimated for the microdetermination of phenylephrine HCl (I) and orphenadrine citrate (II). The proposed methods are based on the formation of ion-pair complexes between the examined drugs with alizarine (Aliz), alizarine red S (ARS), alizarine yellow G (AYG) or quinalizarine (Qaliz), which can be measured at the optimum lambda(max). The optimization of the reaction conditions is investigated. Beer's law is obeyed in the concentration ranges 2-36 microgram ml(-1), whereas optimum concentration as adopted from Ringbom plots was 3.5-33 microgram ml(-1). The molar absorptivity, Sandell sensitivity, and detection limit are also calculated. The correlation coefficient was >/=0.9988 (n=6) with a relative standard deviation of

[Studies on the process of Herba Clinopodii saponins purified with macroporous adsorption resin].

PubMed

Zhang, Yi; Yan, Dan; Han, Yumei

2005-10-01

To study the technological parameters of the purification process of saponins with macroporous adsorption resin. The adsorptive characteristics and elutive parameters of the process were studied by taking the elutive and purified ratio of saponins as markers. 11.4 ml of the extraction of Herba Clinopodii (crude drugs 0.2 g/ml) was purified with a column of macroporous adsorption resin (phi15 mm x H90 mm, dry weight 2.5 g) and washed with 3BV of distilled water, then eluted with 3BV of 30% ethanol and 3BV of 70% ethanol. Most of saponins were collected in the 70% ethanol. With macroporous adsorption resin adsorbing and purifying,the elutive ratio of saponins is 86.8% and the purity reaches 153.2%. So this process of applying macroporous adsorption resin to adsorb and purify Saponins is feasible.

Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro

PubMed Central

Keller, Amy C.; Ma, Jun; Kavalier, Adam; He, Kan; Brillantes, Anne-Marie B.; Kennelly, Edward J.

2012-01-01

The antidiabetic activity of Momordica charantia (L.), Cucurbitaceae, a widely-used treatment for diabetes in a number of traditional medicine systems, was investigated in vitro. Antidiabetic activity has been reported for certain saponins isolated from M. charantia. In this study insulin secretion was measured in MIN6 β-cells incubated with an ethanol extract, saponin-rich fraction, and five purified saponins and cucurbitane triterpenoids from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (1), momordicine I (2), momordicine II (3), 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-β-glucopyranoside (4), and kuguaglycoside G (5). Treatments were compared to incubation with high glucose (27 mM) and the insulin secretagogue, glipizide (50 μM). At 125 μg/ml, an LC-ToF-MS characterized saponin-rich fraction stimulated insulin secretion significantly more than the DMSO vehicle, p=0.02. At concentrations 10 and 25 μg/ml, compounds 3 and 5 also significantly stimulated insulin secretion as compared to the vehicle, p≤0.007, and p= 0.002, respectively. This is the first report of a saponin-rich fraction, and isolated compounds from M. charantia, stimulating insulin secretion in an in vitro, static incubation assay. PMID:22133295

Biosurfactant-enhanced hydrogen production from organic fraction of municipal solid waste using co-culture of E. coli and Enterobacter aerogenes.

PubMed

Sharma, Preeti; Melkania, Uma

2017-11-01

The effect of biosurfactants (surfactin and saponin) on the hydrogen production from organic fraction of municipal solid waste (OFMSW) was investigated using co-culture of facultative anaerobes Enterobacter aerogenes and E. coli. The biosurfactants were applied in the concentration ranges of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 5.0% each. Cumulative hydrogen production (P), maximum hydrogen production rate (Rmax) and lag phases (λ) were analyzed using modified Gompertz model. Results revealed that both the biosurfactants were effective in hydrogen production enhancement. The maximum cumulative hydrogen production of 743.5±14.4ml and 675.6±12.1ml and volumetric hydrogen production of 2.12L H2 /L substrate and 1.93L H2 /L substrate was recorded at 3.5% surfactin and 3.0% saponin respectively. Corresponding highest hydrogen yields were 79.2mlH 2 /gCarbo initial and 72.0mlH 2 /gCarbo initial respectively. Lag phase decreased from 12.5±2.0h at control to a minimum of 9.0±2.8h and 9.5±2.1h at 3.5% surfactin and 3.0% saponin respectively. Volatile fatty acid generation was increased with biosurfactants addition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of vigabatrin in plasma by reversed-phase high-performance liquid chromatography.

PubMed

Tsanaclis, L M; Wicks, J; Williams, J; Richens, A

1991-05-01

A method is described for the determination of vigabatrin in 50 microliters of plasma by isocratic high-performance liquid chromatography using fluorescence detection. The procedure involves protein precipitation with methanol followed by precolumn derivatisation with o-phthaldialdehyde reagent. Separation of the derivatised vigabatrin was achieved on a Microsorb C18 column using a mobile phase of 10 mM orthophosphoric acid:acetonitrile:methanol (6:3:1) at a flow rate of 2.0 ml/min. Assay time is 15 min and chromatograms show no interference from commonly coadministered anticonvulsant drugs. The total analytical error within the range of 0.85-85 micrograms/ml was found to be 7.6% with the within-replicates error of 2.76%. The minimum detection limit was 0.08 micrograms/ml and the minimum quantitation limit was 0.54 micrograms/ml.

In vitro sensitivity of medically significant Fusarium species to various antimycotics.

PubMed

Sekhon, A S; Padhye, A A; Garg, A K; Ahmad, H; Moledina, N

1994-01-01

Sixteen isolates belonging to Fusarium chlamydosporum (n = 4), Fusarium equiseti (n = 1), Fusarium moniliforme (n = 2), Fusarium oxysporum (n = 3), Fusarium proliferatum (n = 1), and Fusarium solani (n = 5) were tested against amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, JAI-amphotericin B (water-soluble compound), hamycin and amphotericin B combined with 5-fluorocytosine, using antibiotic medium M3, high-resolution broth (pH 7.1), Sabouraud's dextrose, and yeast-nitrogen broth media (1 ml/tube). The minimal inhibitory and minimal fungicidal concentrations of 5-fluorocytosine and fluconazole for all species were > 100 micrograms/ml. All Fusarium isolates, except F. equiseti (3.125 micrograms), gave minimal inhibitory concentrations of 12.5-100 micrograms/ml for hamycin. The values for amphotericin B, itraconazole, ketoconazole, JAI-amphotericin B, and amphotericin B combined with 5-fluorocytosine were 1.56-100, 0.78-50, 3.125-100,50-100, and 1.56 to > 100 micrograms/ml, respectively. Although a wide range of minimal inhibitory concentrations was recorded for most of the isolates studied, it appears that some--F. solani, F. oxysporum, F. chlamydosporum, F. equiseti, and F. moliniforme--were more susceptible to amphotericin B, itraconazole, ketoconazole, hamycin, and amphotericin B in the presence of 5-fluorocytosine. All isolates showed resistance to 5-fluorocytosine and fluconazole. The minimal fungicidal concentrations were either the same or several times higher than the minimal inhibitory concentrations.

In vitro ovicidal and larvicidal activities of some saponins and flavonoids against parasitic nematodes of goats.

PubMed

Santos, Acidália Carine Vieira; Santos, Francianne Oliveira; Lima, Hélimar Gonçalves; Silva, Gisele Dias Da; Uzêda, Rosangela Soares; Dias, Êuder Reis; Branco, Alexsandro; Cardoso, Klauber Viana; David, Jorge Mauricio; Botura, Mariana Borges; Costa, Silvia Lima; Batatinha, Maria José Moreira

2018-05-21

This study assessed the anthelmintic activity of plant-derived compounds against gastrointestinal nematodes of goats using the egg hatch and larval motility assays. The compounds tested were saponins (digitonin and aescin) and their respective sapogenins (aglycones), hecogenin acetate and flavonoids (catechin, hesperidin, isocordoin and a mixture of isocordoin and cordoin). Additionally, cytotoxicity of active substances was analysed on Vero cell through 3-4,5-dimethylthiazol-2-yl,2,5diphenyltetrazolium bromide (MTT) and propidium iodide (PI) tests. Significant reduction on the egg hatching (P 90%). Nevertheless, higher cytotoxicity was observed in the MTT assay, with IC50 of 0.20 mg mL-1 (aescin) and 0.0074 mg mL-1 (digitonin). Aescin and digitonin have a pronounced in vitro anthelmintic effect and the glycone portion of these saponins plays an important role in this activity.

[Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) in the pediatric field].

PubMed

Iwai, N; Taneda, Y; Shibata, M; Mizoguchi, F; Katayama, M

1985-02-01

Fundamental and clinical studies on BRL 25000 granules were carried out in the pediatric field. BRL 25000 is a formulation comprising 1 part of clavulanic acid (CVA) and 2 parts of amoxicillin (AMPC). The MICs of BRL 25000 and AMPC were assessed against 24 clinically isolated strains of S. aureus (including 23 beta-lactamase producing strains), 22 S. pyogenes, 20 E. coli (8 beta-lactamase producing strains), 24 K. pneumoniae (24 beta-lactamase producing strains), 20 H. influenzae (6 beta-lactamase producing strains). BRL 25000 showed MIC80 (cumulatively 80% of strains were inhibited) at 6.25 micrograms/ml against S. aureus, less than or equal to 0.10 micrograms/ml against inst S. pyogenes, 12.5 micrograms/ml against E. coli, 6.25 micrograms/ml against K. pneumoniae and 0.39 micrograms/ml against H. influenzae. BRL 25000 showed no improvement in MIC terms against beta-lactamase nonproducing strains compared with AMPC. However, BRL 25000 was markedly more effective against beta-lactamase producing strains. Thus BRL 25000 was up to 8 fold more active against S. aureus, 2 to 64 fold against E. coli, 4 to 128 fold against K. pneumoniae, 4 to 16 fold against H. influenzae than AMPC. Following oral administration of BRL 25000 granules (at a dose level of 12.5 mg/kg) to 2 children aged 9 and 11 years, the mean peak serum concentrations of AMPC and CVA were 8.33 +/- 2.43 micrograms/ml and 4.44 +/- 1.65 micrograms/ml respectively 1 hour after dosing. The half-lives of AMPC and CVA were 1.35 +/- 0.42 hours and 0.91 +/- 0.05 hour, respectively. The urinary excretion was 48.21 +/- 3.83% for AMPC and 16.90 +/- 7.06% for CVA in the first 6 hours after administration. In clinical studies, 23 pediatric patients aged 2 months to 12 years with bacterial infections were treated with BRL 25000 granules and the clinical effectiveness, bacteriological response and side effects were evaluated. The clinical response was assessed in 23 cases, 3 with acute rhinitis, 6 with acute purulent tonsillitis, 5 with acute bronchitis, 4 with acute pneumonia, 3 with impetigo, 1 with furunculosis and 1 with periproctal abscess. Results were excellent in 13 cases, good in 7, fair in 3 and hence the efficacy rate (excellent and good cases) was 87.0% (20/23). In particular the clinical response in 9 cases with infections due to beta-lactamase producing organisms was excellent in 6, good in 2, fair in 1 and the efficacy rate was 88.9% (8/9).(ABSTRACT TRUNCATED AT 400 WORDS)

Dammarane triterpene saponin from Bacopa monniera as the superoxide inhibitor in polymorphonuclear cells.

PubMed

Pawar, R; Gopalakrishnan, C; Bhutani, K K

2001-11-01

The hydroalcoholic extract of the whole plant of Bacopa monniera Wettst. (Scrophulariaceae), exhibited an inhibitory effect on superoxide released from polymorphonuclear (PMN) cells in the nitroblue tetrazolium (NBT) assay. The major saponin bacoside A(3) was found to be responsible for this effect in the herb. This compound showed 85, 91.66, 91.66, and 83 % inhibitions of NBT reduction at the concentrations of 200, 100, 50, and 25 microg/ml, respectively, with an IC(50) value of 10.22 microg/ml. These inhibitory effects were compared with those of the standard positive controls, quercetin and ascorbic acid with IC(50) of 111 and 14.16 microg/ml, respectively. Another major saponin bacopasaponin C was found to be much less potent as compared to bacoside A(3) whereas the remaining two mixtures of saponins were found to be inactive.

Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles.

PubMed

Nabil, Z I; Hussein, A A; Zalat, S M; Rakha, M Kh

1998-03-01

1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.

In vitro interactions between different beta-lactam antibiotics and fosfomycin against bloodstream isolates of enterococci.

PubMed Central

Pestel, M; Martin, E; Aucouturier, C; Lemeland, J F; Caron, F

1995-01-01

The effects of 16 different beta-lactam-fosfomycin combinations against 50 bloodstream enterococci were compared by a disk diffusion technique. Cefotaxime exhibited the best interaction. By checkerboard studies, the cefotaxime-fosfomycin combination provided a synergistic bacteriostatic effect against 45 of the 50 isolates (MIC of cefotaxime at which 90% of the isolates were inhibited, >2,048 micrograms/ml; MIC of fosfomycin at which 90% of the isolates were inhibited, 128 micrograms/ml; mean of fractional inhibitory concentration indexes, 0.195). By killing curves, cefotaxime (at 64 micrograms/ml) combined with fosfomycin (at > or = 64 micrograms/ml) was bactericidal against 6 of 10 strains tested. PMID:8619593

Photohemolytic potency of tetracyclines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bjellerup, M.; Ljunggren, B.

1985-04-01

Hemolysis induced by long-wave ultraviolet radiation (UVA) and 8 different commercial tetracycline derivatives was studied in a model using human red blood cells. Demethylchlortetracycline and doxycycline were shown to have pronounced hemolytic properties causing 88% and 85% hemolysis, respectively, at a concentration of 50 micrograms/ml and 72 J/ cm2 of UVA. Tetracycline, oxytetracycline, and chlortetracycline caused maximally 18% hemolysis at 200 micrograms/ml and lymecycline only 7% at 100 micrograms/ml. Methacycline showed intermediate hemolytic effect of 36% at 200 micrograms/ml. Minocycline had no hemolytic effect whatsoever. These experimental data correlate very well with clinical reports and comparative phototoxicity trials in humans.more » Photohemolysis may thus be of value for predicting tetracycline phototoxicity.« less

Cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii.

PubMed

Yu, Siran; Ye, Xuewei; Chen, Lu; Xie, Xin; Zhou, Qian; Lian, Xiao-Yuan; Zhang, Zhizhen

2015-11-15

Whether sulfated saponins from Holothuria moebii inhibit the proliferation of colorectal cancer cells and have anti-colorectal tumor effects in animal model has not been investigated. To evaluate the cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. (1) Column chromatography was used to prepare the total and individual saponins and HPLC was applied to define the components of the total saponins; (2) the activity of the total and individual saponins inhibiting the proliferation of human colorectal cancer cells was determined by SRB assay and the apoptosis induced by the saponins was qualified using cytometric analysis with Annexin V-FITC/PI double staining; and (3) the antitumor effects of the sulfated saponins on colorectal CT-26 tumor-bearing Balb/c mice were tested. The total and individual sulfated saponins significantly inhibited the proliferation of four different human colorectal cancer cells with IC50 values ranging from 1.04 to 4.08 μM (or 1.46 to 3.24 μg/ml for total saponins) and induced late apoptosis at an early treatment time in cancer cells. The total saponins (120 mg/kg) had antitumor activity in colorectal CT-26 tumor-bearing Balb/c mice. The sulfated saponins from H. moebii remarkably inhibited the proliferation of different human colorectal cancer cells and had significant anti-colorectal tumor activity in animal model. Copyright © 2015 Elsevier GmbH. All rights reserved.

Comparison of high-pressure liquid chromatography and microbiological assay for the determination of biliary elimination of ciprofloxacin in humans.

PubMed Central

Brogard, J M; Jehl, F; Monteil, H; Adloff, M; Blickle, J F; Levy, P

1985-01-01

Serum kinetics and biliary, urinary, and fecal elimination of ciprofloxacin, a new quinolone derivative, were studied in 12 recently cholecystectomized patients provided with T-tube drainage during 24 h after oral administration of a single 500-mg dose of this substance. Drug concentrations were measured by both high-pressure liquid chromatography (HPLC) and microbiological assay. The results were comparable for the concentrations in serum (average of peaks, 2.0 +/- 0.2 micrograms/ml by HPLC and 2.3 +/- 0.3 micrograms/ml by the microbiological method) and urine (0 to 6 h, 267 +/- 74 and 241 +/- 58 micrograms/ml, respectively). This was not the case for biliary values, for which the microbiological assay yielded significantly higher concentrations than did HPLC (average of peak concentrations, 21.2 +/- 2.6 and 16.0 +/- 2.5 micrograms/ml, respectively [P less than 0.02]), nor for total 24-h biliary output (2,167 +/- 288 and 1,587 +/- 222 micrograms, respectively [P less than 0.01]). This suggests hepatic biotransformation of ciprofloxacin into microbiologically active metabolites. The apparent broad antibacterial spectrum of ciprofloxacin and its higher biliary levels than simultaneously determined serum concentrations suggest that this derivative is suitable for the treatment of biliary tract infections. PMID:2939796

[Laboratory and clinical studies on flomoxef in neonates and premature infants].

PubMed

Motohiro, T; Maruoka, T; Nagai, K; Oki, S; Tsumura, N; Sasaki, H; Aramaki, M; Koga, T; Sakata, Y; Tominaga, K

1993-07-01

Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Antihyperglycemic Potential of Saponin-enriched Fraction from Pithecellobium dulce Benth. Seed Extract

PubMed Central

Kumar, Mahesh; Govindrajan, Jeyabalan; Nyola, Narendra Kumar

2017-01-01

Background: Indian traditional system of medicine uses Pithecellobium dulce for the treatment of diabetes mellitus. Objectives: This study aims to develop an extract rich in saponins derived from seeds of the plant and to evaluate its antihyperglycemic potential in vitro and in vivo. Materials and Methods: Defatted seeds were extracted with methanol and processed to afford saponin-enriched fraction (Pithecellobium dulce saponin-enriched fraction [PDSEF]). This fraction was evaluated for its potential to inhibit enzymes such as α-glucosidase and α-amylase, in vitro. The fraction was subjected to oral toxicity study followed by in vivo sucrose tolerance test. An analytical high-performance liquid chromatography method was developed for fingerprinting of the fraction. Results: The method adopted for enrichment of saponins was robust enough to enrich saponin content to 96.37% ±1.21% w/w. PDSEF displayed superior inhibition of enzymes (α-glucosidase and α-amylase with IC50 of 5.12 ± 0.15 μg/ml and 17.28 ± 0.23 μg/ml, respectively) compared to acarbose. It was found to be safe in mice up to 2000 mg/kg and significantly prevented blood glucose level in sucrose tolerance test by inhibiting enzymes responsible for hydrolysis of sucrose. Conclusion: PDSEF displayed excellent antihyperglycemic activity in vitro and in vivo and should be evaluated further to develop it as a promising drug for the management of diabetes mellitus. SUMMARY Saponin enriched fraction from P. dulce seeds showed significant inhibition of key enzymes responsible for digestion of polysaccharides. The saponin enriched fraction was found to be safe in mice and prevented blood glucose level in mice in sucrose tolerance test. Abbreviations Used: PDSEF: Pithecellobium dulce saponin-enriched fraction, IC50: Inhibitory concentration 50, HPLC: High performance liquid chromatography PMID:29333038

Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine.

PubMed Central

Panpitpat, C.; Thisyakorn, U.; Chotpitayasunondh, T.; Fürer, E.; Que, J. U.; Hasler, T.; Cryz, S. J.

2000-01-01

Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml. The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005). Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline. These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T antibody levels after immunization. PMID:10812736

[Experimental and clinical evaluation latamoxef in newborn and premature infants].

PubMed

Toyonaga, Y; Kurosu, Y; Sugita, M; Kitagawa, M; Hori, M

1983-09-01

Basic and clinical studies of latamoxef (LMOX) were carried out in neonates. In basic study, these neonates consisted of 16 mature babies and 12 premature babies. LMOX was administered at dose of 10 and 20 mg/kg, either as a single intravenous injection or as a 60 minutes intravenous drip infusion. Both the mature babies and the premature babies were divided into 3 subgroups as a function of the number of days after birth (0--3, 4--7 and 8--25 days). A clinical study of LMOX was performed in 12 neonates aged between 0--35 days, consisting 6 males and 6 females. (Purulent meningitis 4 cases, septicemia 1 case, bronchopneumonia 5 cases, pertussis pneumonia 1 case, urinary tract infection 1 case). Serum concentration and urinary excretion 10 mg/kg, one shot intravenous injection In the 3 subgroups of neonates the peak serum concentrations of LMOX were found to range from 14.6 to 28.9 micrograms/ml. Although there was no significant difference, the half-life of the drug became shorter as the age of the neonates increased, these values were 4.46, 3.85 and 3.30 hours, respectively. 10 mg/kg, 60 minutes intravenous drip infusion. As above, the peak LMOX serum concentrations were found to range from 23.7 to 38.9 micrograms/ml, the half-lives of the 3 subgroups were 4.83, 2.48 and 3.01 hours, respectively. And urinary excretions were ranged from 46.0 to 56.5% for 6 hours. 20 mg/kg, one shot intravenous injection The peak serum concentrations were found to range from 31.0--82.5 micrograms/ml, and it was found out 3.29--15.9 micrograms/ml at 8 hours after the injection. There was a tendency for the half-life to be shorter in more mature subjects in 3 subgroups. 20 mg/kg, 60 minutes intravenous drip infusion In the 3 subgroups, the peak concentration was the level existing at the end of the intravenous drip infusion, and that showed a range of 41.8--58.6 micrograms/ml. Half-lives were found out the significant difference to their age, these showed 4.08, 2.31 and 2.52 hours. Cerebrospinal fluid concentrations of LMOX Cerebrospinal fluid concentrations of LMOX were studied in 2 cases at the dose about 50 mg/kg. In 1 case, that's meningitis estimated E. coli organism, the cerebrospinal fluid concentrations of LMOX were found to range from 29.0 to 49.9 micrograms/ml in that acute state. In another case from N. meningitidis, that values were found to range 12.1 to 21.3 micrograms/ml. These cerebrospinal levels were superior value at it's penetration ratio. Clinical studies.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro activity of flumequine in comparison with several other antimicrobial agents against five pathogens isolated in calves in The Netherlands.

PubMed

Mevius, D J; Breukink, H J; van Miert, A S

1990-10-01

The in vitro activity of flumequine in comparison with several other drugs was tested against 17 P. multocida, 16 P. haemolytica, 21 S. dublin, 21 S. typhimurium and 21 E. coli strains, isolated in (veal) calves in the Netherlands. The MIC50 of flumequine for the respective pasteurellas was 0.25 and 1 microgram/ml, for the salmonellas and E. coli 0.5 micrograms/ml. In comparison with flumequine, enrofloxacin and ciprofloxacin showed higher in vitro activity, with MIC50 less than or equal to 0.008 micrograms/ml for ciprofloxacin. Decreased susceptibility of the pasteurellas was found for kanamycin, neomycin, streptomycin, gentamicin, oxytetracycline and doxycycline. The MIC50 of minocycline for P. multocida was 0.5 micrograms/ml and there was no cross resistance with the other tetracyclines. P. multocida was very susceptible to ampicillin (MIC50 less than or equal to 0.03 micrograms/ml), P. haemolytica, however, was 100% resistant to this drug. Both pasteurellas were susceptible to cephalothin and approximately 50% of the strains of both bacteria were resistant to chloramphenicol. The MIC50 of either spiramycin or tylosin was greater than or equal to their respective breakpoint-MIC values. Both pasteurellas were susceptible to the combination of trimethoprim and sulphamethoxazole. However, for P. multocida, the addition of sulphamethoxazole to trimethoprim had no synergistic effect on its MIC. In comparison with trimethorpim, aditoprim was less potent. Therefore only P. multocida was susceptible to aditoprim.

[Studies on flomoxef in the perinatal period].

PubMed

Cho, N; Fukunaga, K; Kunii, K; Kobayashi, I

1991-06-01

Pharmacokinetic, bacteriological and clinical studies on flomoxef (FMOX) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of FMOX on the growth of methicillin-resistant Staphylococcus aureus (MRSA, MIC 400 micrograms/ml), methicillin-sensitive S. aureus (MSSA, MIC 0.78 microgram/ml), Escherichia coli (MIC 3.13 micrograms/ml and MIC 0.20 microgram/ml) in amniotic fluid were determined and it was found that the activity of FMOX was enhanced in the amniotic fluid. FMOX rapidly penetrated into tissues and sera of pregnant women upon intravenous injection and its maternal serum concentrations reached their peak levels shortly after administration. Placental penetration of FMOX to the fetus was good and, after single intravenous injection of 1 g, the concentrations of FMOX in the umbilical cord serum and amniotic fluid exceeded MICs against major causative organisms of perinatal infections. These results indicate that single intravenous injection of FMOX 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of FMOX for the treatment of 14 cases of puerperal infections showed excellent clinical effectiveness with 100% clinical effect and 81.8% bacteriological response. No side-effect was observed in any case. All of these results suggested clinical usefulness of FMOX in the perinatal period.

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

PubMed

Niitsuma, K; Saitoh, M; Kojimabara, M; Kashiwabara, N; Aoki, T; Tomizawa, M; Maeda, J; Kosenda, T

2001-02-01

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

Cytotoxic activity of a methanol extract of Phallusia nigra (Tunicata, Ascidiacea).

PubMed

Costa, L V; Malpezzi, E L; Matsui, D H; Machado-Santelli, G M; Freitas, J C

1996-03-01

Tunicates have been reported to be a rich source of biologically active compounds. In this study, we demonstrate the presence of cytotoxic substances in Phallusia nigra, a common tunicate from Brazilian coastal waters. An extract of tunicate tissue was obtained by homogenizing the visceral organs from 50 specimens in methanol, followed by filtration and concentration in a rotary vacuum evaporator. Finally, the concentrate was partitioned with chloroform to remove lipids. The resulting extract possessed antimitotic and hemolytic activity. The former was demonstrated as a delay in the development of sea urchin eggs by partially inhibiting the process of cleavage (first cleavage, EC50 +/- SEM = 3.44 +/- 0.84 mg/ml). The < 500 molecular fraction of the extract obtained by ultrafiltration also inhibited cell proliferation (the number of viable cells was decreased by 68% with 500 micrograms/ml) and DNA synthesis of T47D cells derived from human breast carcinoma as measured by [3H]-thymidine incorporation (66% of the control value after 24-h incubation with 100 micrograms/ml). Dose-dependent hemolysis obtained with P. nigra extract on mouse erythrocytes had an EC50 +/- SEM = 1.12 +/- 0.02 mg/ml for a 0.5% erythrocyte suspension. Hemolysis could be reduced by pre-incubating the cells with choline-containing phospholipid. Sphingomyelin (40 micrograms/ml) increased the EC50 by two-fold to 2.86 +/- 0.04 mg/ml, but phosphatidylcholine (80 micrograms/ml) did not modify hemolysis.

Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells

PubMed Central

Stefanowicz-Hajduk, Justyna; Bartoszewski, Rafal; Bartoszewska, Sylwia; Kochan, Kinga; Adamska, Anna; Kosiński, Igor; Ochocka, J. Renata

2015-01-01

Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death. PMID:26295969

In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

PubMed Central

Fass, R J

1991-01-01

The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous. PMID:1903912

[Investigation on the process of sapindus saponin purified with macroporous adsorption resin and screening of its bacteriostasis].

PubMed

Fu, Yong; Lei, Peng; Han, Yu-mei; Yan, Dan

2010-02-01

To study the technological parameters of the purification process of saponins with macroporous adsorption resin. The adsorptive characteristics and elutive parameters of the process were studied by taking the elutive and purified ratio of saponins as markers. Bacteriostasis activity of each parts eluted was evaluated by the mean of cup-plate method. 13.6 mL of the extraction of sapindus saponin (crude drugs 0.01 g/mL) was purified with a column of macroporous adsorption resin (phi15 mm x H90 mm, dry weight 2.5 g) and washed with 3BV of distilled water, then eluted with 3BV of 30% ethanol and 3BV of 70% ethanol, most of saponins were collected in the 70% ethanol. With macroporous adsorption resin adsorbing and purifying, the elutive ratio of saponins was 93.8% and the purity reached 250.1%. So this process of applying macroporous adsorption resin to adsorb and purify saponins is feasible, and supplies reference to the purification of other types of saponin.

[Study on a new cephamycin preparation cefminox in the field of pediatrics].

PubMed

Sato, H; Hirama, Y; Narita, A; Nakazawa, S; Suzuki, H; Matsumoto, K; Tazoe, K; Chikaoka, H; Nakazawa, S

1985-03-01

Cefminox (CMNX, MT-141) was studied both fundamentally and clinically in the field of pediatrics with following results. The MIC of CMNX for Bordetella pertussis was 0.10 micrograms/ml in inoculum size 10(6) cells/ml. Following administration of 10 and 20 mg/kg of CMNX as drip infusion over 1 hour, the blood levels of the drug were 49.0 +/- 18.1 and 69.1 micrograms/ml at completion of infusion, 28.8 +/- 7.7 and 61.6 micrograms/ml at 1.5 hours, 23.6 +/- 9.3 and 44.1 +/- 3.8 micrograms/ml at 2 hours and 1.4 +/- 1.4 and 4.0 +/- 0.6 micrograms/ml at 7 hours, with T1/2 of 1.03 and 1.41 +/- 0.03 hours, respectively. Within the first 7 hours after administration, 61.4 +/- 8.2 and 55.9 +/- 0.8% of the drug dosed were excreted at active form in urine. In child with encephalitis, drug considered to be good as a cephem antibiotic was achieved in the cerebrospinal fluid (the ratio of the level in the cerebrospinal fluid to that in the serum was 7.3%). In addition, in the pus in empyema also high level was reached (its ratio against blood level was 53%). In the treatment of 31 cases of acute infections of pediatric field including upper and lower airway infections, empyema, whooping cough, acute urinary tract infections and phlegmon, CMNX was administered intravenously either as one shot injection as drip infusion. The clinical results obtained were rated as good or more in 93% of the cases and as fair or more in 100% of the cases. The main dosage of CMNX in these cases was about 60 to 70 mg/kg per day in 2 or 3 divided doses. S. aureus, S. pyogenes, S. pneumoniae, H. influenzae and ABPC resistant strain of E. coli demonstrated in various materials could be eradicated after intravenous injection of CMNX. CMNX was administrated for a period of 2 to 16 days to a total amount of 1.5 to 26.5 g. In none of these cases side effects developed nor any abnormality was revealed by hematological findings or results of renal or liver function.

Agelasine F from a Philippine Agelas sp. sponge exhibits in vitro antituberculosis activity.

PubMed

Mangalindan, G C; Talaue, M T; Cruz, L J; Franzblau, S G; Adams, L B; Richardson, A D; Ireland, C M; Concepcion, G P

2000-05-01

Marine sponge samples were collected in Baler, Aurora, Philippines, and extracts were tested for in vitro antituberculosis activity. An orange Agelas sp. sponge yielded the known compound, agelasine F, which inhibited some drug resistant strains of Mycobacterium tuberculosis in vitro at concentrations as low as 3.13 micrograms/ml. Activity against M. tuberculosis residing within macrophages required concentrations of 13-22 micrograms/ml which was below the IC50 for Vero cells (34 micrograms/ml).

Phorbol 12,13-dibutyrate and 1-oleyl-2-acetyldiacylglycerol stimulate inositol trisphosphate dephosphorylation in human platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina y Vedia, L.M.; Lapetina, E.G.

1986-08-15

Inositol trisphosphate (IP3) is formed in response to specific agonists that cause activation of phospholipase C and degradation of phosphatidylinositol bisphosphate. IP3 is a second messenger that releases Ca/sup 2 +/ from the dense tubular system to the cytosol in stimulated platelets. Our present information indicates that (/sup 3/H)IP3 is dephosphorylated to (/sup 3/H)inositol bisphosphate (IP2) and (/sup 3/H)inositol monophosphate (IP) by human platelets treated with 0.05-0.10% Triton X-100. This dephosphorylation of (/sup 3/H)IP3 to (/sup 3/H)IP2 and (/sup 3/H)IP is also observed when platelets are permeabilized by electrical stimulation or by 20 micrograms/ml saponin. These detergents or electropermeabilization allowmore » IP3 to access cytosolic IP3 phosphatase. Pretreatment of intact platelets with phorbol dibutyrate and 1-oleyl-2-acetyldiacylglycerol for 30 s, at concentrations that maximally activate protein kinase C, stimulates the conversion of IP3 to IP2 and IP. This suggests a role for protein kinase C in the regulation of IP3 degradation.« less

Formulation and evaluation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd.

PubMed

Nesseem, D I; Michel, C G; Sleem, A A; El-Alfy, T S

2009-02-01

This study deals with the formulation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd. A bioactivity guided fractionation of different leaf extracts [defatted ethanol 70% (a), butanol (b), ethanol 70% (c), ethyl acetate (d) and petroleum ether (e) extracts] revealed that extract (c) possessed the highest antihyperglycemic activity followed by (b) and (a). HPLC was adopted for standardization of the extract (c) based on evaluation of the major saponin christinin-A which was used as marker. The detection limit was 9.45 mg/ml for Christinin-A. Extracts (a), (b) and (c) were separately formulated in soft (S) and hard (H) gelatin capsules. Two different formulations (F1 and F2) were tried using different excipients suitable for oral drug delivery. Formula 1, used for soft gelatin capsules [(F1) Sa, Sb, Sc] Formula 2, used for hard gelatin capsules [(F2) - Ha, Hb, Hc]. The recovery rates of the samples of saponin were in the range 99.43-101.86% at 200, 800 microg/ml and 1200 microg/ml. Saponin release rates from different formulae were carried out using dissolution tester USP XXIV. The highest release was obtained from formulation Sc. The release of the extracts followed diffusion mechanism. The selected formula Sc exhibited highest anti-diabetic activity (P < 0.01) on acute and long-term administration and highest saponin release. This formula (Sc) contained poly-oxyethylene (20) cetyl ether (BC-20TX), PEG 400, PEG 6000, purified water, meglyol 810, ascorbic acid and 200 mg of extract (c).

Radionuclides in ground water at the Idaho National Engineering Laboratory, Idaho

USGS Publications Warehouse

Knobel, LeRoy L.; Mann, Larry J.

1988-01-01

Sampling for radionuclides in groundwater was conducted at the Idaho National Engineering Laboratory during September to November 5 1987. Water samples from 80 wells that obtain water from the Snake River Plain aquifer and 1 well that obtains water from a shallow, discontinuous perched-water body at the Radioactive Waste Management Complex were collected and analyzed for tritium, strontium-90, plutonium-238, plutonium-239, -240 (undivided), americium-241, cesium-137, cobalt-60, and potassium-40--a naturally occurring radionuclide. The groundwater samples were analyzed at the Idaho National Engineering Laboratory in Idaho. Tritium and strontium-90 concentrations ranged from below the reporting level to 80.6 +/-0.000005 and 193 +/-5x10 to the minus eight micrograms Ci/ml, respectively. Water from a disposal well at Test Area North--which has not been used to dispose of waste water since September 1972--contained 122 +/-9x10 to the minus eleven micrograms Ci/ml of plutonium-238, 500 +/-20x10 to the minus eleven of plutonium-239, -240 (undivided), 21 +/-4x10 to the minus eleven micrograms Ci/ml of americium-241, and 750 +/-20x10 to the minus eight micrograms Ci/ml cesium-137; the presence of these radionuclides was verified by resampling and reanalysis. The disposal well had 8.9 +/-0.0000009 micrograms Ci/ml of cobalt-60 on October 28, 1987, but cobalt-60 was not detected when the well was resampled on January 11, 1988. Potassium-40 concentrations were less than the reporting level in all wells. (USGS)

[The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

PubMed

Yamaguchi, H; Igari, J; Kume, H; Abe, M; Oguri, T; Kanno, H; Kawakami, S; Okuzumi, K; Fukayama, M; Ito, A; Kawata, K; Uchida, K

1997-09-01

The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

Effect of chloramphenicol on sister chromatid exchange in bovine fibroblasts.

PubMed

Arruga, M V; Catalan, J; Moreno, C

1992-03-01

The genotoxic potential of different chloramphenicol concentrations (5, 20, 40 and 60 micrograms ml-1) was investigated in bovine fibroblast primary lines by sister chromatid exchange assay. Chloramphenicol acted for long enough to ensure similar effects to persistent storage in the kidney. In this experiment 10 micrograms ml-1 of 5-bromodeoxyuridine was added for 60 hours for all doses of chloramphenicol and to the control. When the tissue culture cells were exposed to increasing doses, increased numbers of sister chromatid exchanges developed. Differences were significantly different to the control.

In vitro activity of FK037, a new parenteral cephalosporin, against anaerobic bacteria.

PubMed Central

Kato, N; Kato, H; Tanaka, Y; Bando, K; Watanabe, K; Ueno, K

1993-01-01

The activity of FK037, a new parenteral cephalosporin, was compared with those of cefpirome, ceftazidime, and flomoxef against 322 recent clinical isolates of anaerobic bacteria. A fastidious facultative anaerobe, Gardnerella vaginalis, was also studied. FK037 inhibited 90% of isolates of Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Clostridium perfringens, Mobiluncus spp., G. vaginalis, and Porphyromonas gingivalis at < or = 0.78 micrograms/ml. The MICs of FK037 for 50 and 90% of Bacteroides fragilis isolates were 25 and > 200 micrograms/ml, respectively; the activity of FK037 was comparable to those of cefpirome and ceftazidime but lower than that of flomoxef. The activity of FK037 against Fusobacterium nucleatum, Fusobacterium varium, and Bilophila wadsworthia decreased when inoculum size was increased from 10(6) to 10(8) CFU/ml. Little influence of inoculum size on the activity of FK037 was observed for other isolates tested. Medium pH affected the activity of FK037 against F. varium (MICs at pHs 5 and 7, 3.13 and 100 micrograms/ml, respectively) and Bacteroides gracilis (MICs at pHs 5 and 7, 12.5 and 1.56 micrograms/ml, respectively) but not against other organisms tested. FK037 was less resistant than flomoxef to hydrolysis by beta-lactamase group 2e derived from B. fragilis GAI 0558 and GAI 10150. PMID:8517721

Environmentally safe sewage sludge disposal: the impact of liming on the behaviour of Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn.

PubMed

Scancar, J; Milacic, R; Strazar, M; Burica, O; Bukovec, P

2001-02-01

Dewatered sewage sludge containing relatively high total concentrations of Cr (945 micrograms ml-1), Cu (523 micrograms ml-1), Ni (1186 micrograms ml-1) and Zn (2950 micrograms ml-1) was treated with quicklime and sawdust for sludge disinfection and post-stabilisation. The mobility of the heavy metals in the sludge samples was assessed by applying a modified five-step Tessier sequential extraction procedure. Water was added as a first step for estimation of the proportion of the easily soluble metal fractions. To check the precision of the analytical work the concentrations of heavy metals in steps 1-6 of the extraction procedure were summed and compared to the total metal concentrations. The mass balance agreed within +/- 3% for Cd, Cu, Cr, and Zn and within +/- 5% for Ni, Pb, Fe and Mn. Data from the partitioning study indicate that in the lime-treated sludge at a pH of 12 the mobility of Cu and Ni notably increased with the solubilisation of these metals from their organic and/or carbonate and Fe and Mn oxide and hydroxide fractions, respectively. Liming slightly decreased the proportion of other heavy metals in the easily soluble fractions while its impact on the partitioning between other sludge phases was almost insignificant. Due to the increased solubility of Ni and Cu as well as potential Cr oxidation at high pH, liming cannot be recommended for sludge disinfection. Addition of sawdust did not change the heavy metal partitioning.

In vitro susceptibility of Giardia lamblia trophozoites to metronidazole and tinidazole.

PubMed

Jokipii, L; Jokipii, A M

1980-03-01

The number of motile Giardia lamblia trophozoites approximately doubled in axenic culture in 24 hr when 50% fresh medium was provided every 24 hr. In a microculture modification involving no change of medium, similar multiplication took place during the first 24 hr, and trophozoites remained motile for four days or longer. Metronidazole and tinidazole were active against G. lamblia in vitro, an observation suggesting that their effect in therapy of giardiasis is a direct one. The effect was rapid--high drug concentrations immobilized most trophozoites within 3.5 hr. There was an inverse relationship between duration of exposure and concentration of drug needed for significant immobilization: the effect of 0.1 microgram/ml was detectable after two to four days. Tinidazole was 4.4-fold as active as metronidazole; the minimal concentrations that immobilized 100% of trophozoites by 24 hr ranged from 0.2 to 12.5 microgram/ml and from 1.6 to 50 microgram/ml, respectively.

Inhibitory effects of anethole and eugenol on the growth and toxin production of Aspergillus parasiticus.

PubMed

Karapinar, M

1990-05-01

The antifungal and antiaflatoxigenic activity of anethole and eugenol which are active components of commonly used spices was studied against two strains of Aspergillus parasiticus. Anethole, up to concentration of 400 micrograms/ml where complete inhibition was observed, delayed growth and reduced mycelial weight but it showed a stimulative effect on the toxin production of both strains. At a concentration of 300 micrograms/ml, eugenol inhibited the growth of both strains; levels of eugenol below 200 micrograms/ml enhanced production of aflatoxin particularly by A. parasiticus NRRL 299.

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

PubMed

Smith, C; McEwan, A I; Jhaveri, R; Wilkinson, M; Goodman, D; Smith, L R; Canada, A T; Glass, P S

1994-10-01

We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

Eurotium (Aspergillus) repens metabolites and their biological activity.

PubMed

Podojil, M; Sedmera, P; Vokoun, J; Betina, V; Baráthová, H; Duracková, Z; Horáková, K; Nemec, P

1978-01-01

Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mor7 tality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.

Simultaneous determination of triterpenoid saponins in dog plasma by a validated UPLC-MS/MS and its application to a pharmacokinetic study after administration of total saponin of licorice.

PubMed

Tao, Weiwei; Duan, Jinao; Guo, Jianming; Li, Jianping; Tang, Yuping; Liu, Pei; Yang, Nianyun

2013-03-05

A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of eight constituents, uralsaponin C, uralsaponin F, 22β-acetoxyl-glycyrrhizin, 24-hydroxy-licorice-saponin E2, licorice-saponin G2, licorice-saponin E2, glycyrrhizin, and licorice-saponin J2, from total saponin of licorice (TSL) in dog plasma. Ardisiacrispin A was used as the internal standard (IS). The separation was performed on Thermo Syncronic C₁₈ column (100 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.4 mL min⁻¹, and acetonitrile/methanol (3:1, v/v)-0.1% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with negative ionization mode. All calibration curves had good linearity (r>0.991) over the concentration range from 2.03-405 ng mL⁻¹ to 2.63-2625 ng mL⁻¹ for all components. The intra- and inter-day precision was within 15% and the accuracy ranged from -14.08% to 13.8%. The method was successfully applied to pharmacokinetic study of eight triterpenoid saponins in dog plasma after oral administration of TSL. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Drug-induced in vitro inhibition of neutrophil-endothelial cell adhesion.

PubMed Central

Pellegatta, F.; Lu, Y.; Radaelli, A.; Zocchi, M. R.; Ferrero, E.; Chierchia, S.; Gaja, G.; Ferrero, M. E.

1996-01-01

1. Leukocyte-endothelial cell interactions play an important role during ischaemia-reperfusion events. Adhesion molecules are specifically implicated in this interaction process. 2. Since defibrotide has been shown to be an efficient drug in reducing damage due to ischaemia-reperfusion in many experimental models, we analysed the effect of defibrotide in vitro on leukocyte adhesion to endothelial cells in basal conditions and after their stimulation. 3. In basal conditions, defibrotide (1000 micrograms ml-1) partially inhibited leukocyte adhesion to endothelial cells by 17.3% +/- 3.6 (P < 0.05), and after endothelial cell stimulation (TNF-alpha, 500 u ml-1) or after leukocyte stimulation (fMLP, 10(-7) M), it inhibited leukocyte adhesion by 26.5% +/- 3.4 and 32.4% +/- 1.8, respectively (P < 0.05). 4. In adhesion blockage experiments, the use of the monoclonal antibody anti-CD31 (5 micrograms ml-1) did not demonstrate a significant inhibitory effect whereas use of the monoclonal antibody anti-LFA-1 (5 micrograms ml-1) significantly interfered with the effect of defibrotide. 5. This result was confirmed in NIH/3T3-ICAM-1 transfected cells. 6. We conclude that defibrotide is able to interfere with leukocyte adhesion to endothelial cells mainly in activated conditions and that the ICAM-1/LFA-1 adhesion system is involved in the defibrotide mechanism of action. PMID:8762067

Leishmanicidal activity of saponins isolated from the leaves of Eclipta prostrata and Gymnema sylvestre.

PubMed

Khanna, Venkatesan Gopiesh; Kannabiran, Krishnan; Getti, Giulia

2009-02-01

To evaluate the leishmanicidal activity of saponin, dasyscyphin C of Eclipta prostrata and sapogenin, gymnemagenol from Gymnema sylvestre leaves under in vitro conditions. Dasyscyphin C/Gymnemagenol were dissolved in phosphate buffered saline (PBS) and diluted with liquid medium to obtain concentrations ranging from 1000 to 15 mug /ml. The leishmanicidal activity against leishmanial parasites, Leishmania major, Leishmania aethiopica and Leishmania tropica promastigotes was studied by the MTS assay. The Dasyscyphin C isolated from E. prostrata showed good leishmanicidal activity at 1000mug/ml concentration, with the IC(50) value of 450mug/ml against L. major promastigote and the percentage of parasitic death was 73; whereas, gymnemagenol of G. sylvestre showed only 52% parasitic death at 1000 mug/ml concentration. The other Leishmania species, L. aethiopica and L. tropica promastigotes, were less sensitive to the saponins of E. prostrata and G. sylvestre. From this study, it can be concluded that the dasyscyphin C of E. prostrata has significant leishmanicidal activity against L. major promastigote.

Synthetic Studies of Complex Immunostimulants from Quillaja saponaria: Synthesis of the Potent Clinical Immunoadjuvant QS-21Aapi

PubMed Central

Kim, Yong-Jae; Wang, Pengfei; Navarro-Villalobos, Mauricio; Rohde, Bridget D.; Derryberry, JohnMark; Gin, David Y.

2008-01-01

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21Aapi in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues. PMID:16953631

Detection of relatively penicillin G-resistant Neisseria meningitidis by disk susceptibility testing.

PubMed Central

Campos, J; Mendelman, P M; Sako, M U; Chaffin, D O; Smith, A L; Sáez-Nieto, J A

1987-01-01

Beginning in 1985, relatively penicillin G-resistant (Penr) meningococci which did not produce beta-lactamase were isolated from the blood and cerebrospinal fluid of patients in Spain. We identified 16 Penr (mean MIC, 0.3 microgram/ml; range, 0.1 to 0.7 microgram/ml) and 12 penicillin-susceptible (Pens; mean MIC, less than or equal to 0.06 microgram/ml) strains of Neisseria meningitidis by the agar dilution technique using an inoculum of 10(4) CFU and questioned which disk susceptibility test would best differentiate these two populations. We compared the disk susceptibility of these strains using disks containing 2 (P2) and 10 (P10) U of penicillin G, 2 (Am2) and 10 (Am10) micrograms of ampicillin, and 1 microgram of oxacillin (OX1). We also investigated susceptibility with disks containing 30 micrograms of each of cephalothin (CF30), cefoxitin (FOX30), cefuroxime (CXM30), and cefotaxime (CTX30) and 75 micrograms of cefoperazone (CFP75) and determined by cluster analysis any correlation with the zone diameters obtained with P2 disks. Using the P2 and AM2 disks (in contrast to the P10 and AM10 disks), we correctly differentiated all the Penr from Pens isolates. In addition, the zone diameters with the P2 disk gave the best correlation with the penicillin G MIC determinations. All 16 Penr strains and 3 of 12 Pens strains showed zone diameters of 6 mm around OX1 disks, limiting the usefulness of OX1 disks. The zone diameters obtained with CF30, CXM30, and OX1 disks correlated with those obtained with the P2 disk, which suggests that these antibiotics have similar effects on these strains. In contrast, the data obtained with FOX30, CTX30, and CFP75 disks did not cluster with those obtained with the P2 disk, which suggests that there was a difference in the bacterial target or reflects their greater activity. We conclude that the P2 disk tests more readily identify Penr meningococci than do the standard P10 disk tests. PMID:3124729

Physiological and structural properties of saponin-skinned single smooth muscle cells

PubMed Central

1987-01-01

The study of the fundamental events underlying the generation and regulation of force in smooth muscle would be greatly facilitated if the permeability of the cell membrane were increased so that the intracellular environment of the contractile apparatus could be manipulated experimentally. To initiate such an analysis, we developed a saponin permeabilization procedure that was used to "skin" isolated smooth muscle cells from the stomach of the toad, Bufo marinus. Suspensions of single cells isolated enzymatically were resuspended in high-K+ rigor solution (0 ATP, 5 mM EGTA) and exposed for 5 min to 25 micrograms/ml saponin. Virtually all the cells in a suspension were made permeable by this procedure and shortened to less than one-third their initial length when ATP and Ca++ were added; they re-extended when free Ca++ was removed. Analysis of the protein content of the skinned cells revealed that, although their total protein was reduced by approximately 30%, they retained most of their myosin and actin. Skinning was accompanied by a rearrangement of actin and myosin filaments within the cells such that a fine fibrillar structure became visible under the light microscope and a tight clustering of acting filaments around myosin filaments was revealed by the electron microscope. Face-on views of saponin-treated cell membranes revealed the presence of 70-80-A-wide pits or holes. The shortening rate of skinned cells was sensitive to [Ca++] between pCa 7 and pCa 5 and was half-maximal at approximately pCa 6.2. Shortening was also dependent on [ATP] but could be increased at low [ATP] by pretreatment with adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), which suggests that myosin phosphorylation was more sensitive to low substrate concentrations than was cross-bridge cycling. To determine whether a significant limitation to free diffusion existed in the skinned cells, a computer model of the cell and the unstirred layer surrounding it was developed. Simulations revealed that the membrane, even in skinned cells, could, for short time intervals, significantly inhibit the movement of substances into and out of cells. PMID:3114416

Physiological and structural properties of saponin-skinned single smooth muscle cells.

PubMed

Kargacin, G J; Fay, F S

1987-07-01

The study of the fundamental events underlying the generation and regulation of force in smooth muscle would be greatly facilitated if the permeability of the cell membrane were increased so that the intracellular environment of the contractile apparatus could be manipulated experimentally. To initiate such an analysis, we developed a saponin permeabilization procedure that was used to "skin" isolated smooth muscle cells from the stomach of the toad, Bufo marinus. Suspensions of single cells isolated enzymatically were resuspended in high-K+ rigor solution (0 ATP, 5 mM EGTA) and exposed for 5 min to 25 micrograms/ml saponin. Virtually all the cells in a suspension were made permeable by this procedure and shortened to less than one-third their initial length when ATP and Ca++ were added; they re-extended when free Ca++ was removed. Analysis of the protein content of the skinned cells revealed that, although their total protein was reduced by approximately 30%, they retained most of their myosin and actin. Skinning was accompanied by a rearrangement of actin and myosin filaments within the cells such that a fine fibrillar structure became visible under the light microscope and a tight clustering of acting filaments around myosin filaments was revealed by the electron microscope. Face-on views of saponin-treated cell membranes revealed the presence of 70-80-A-wide pits or holes. The shortening rate of skinned cells was sensitive to [Ca++] between pCa 7 and pCa 5 and was half-maximal at approximately pCa 6.2. Shortening was also dependent on [ATP] but could be increased at low [ATP] by pretreatment with adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), which suggests that myosin phosphorylation was more sensitive to low substrate concentrations than was cross-bridge cycling. To determine whether a significant limitation to free diffusion existed in the skinned cells, a computer model of the cell and the unstirred layer surrounding it was developed. Simulations revealed that the membrane, even in skinned cells, could, for short time intervals, significantly inhibit the movement of substances into and out of cells.

Improved micromethod for mezlocillin quantitation in serum and urine by high-pressure liquid chromatography.

PubMed Central

Fiore, D; Auger, F A; Drusano, G L; Dandu, V R; Lesko, L J

1984-01-01

A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove interfering substances from samples before chromatography. Quantitation included the use of an internal standard, nafcillin. Mezlocillin was chromatographed with a phosphate buffer-acetonitrile (73:27) mobile phase and a C-18 reverse-phase column and detected at a wavelength of 220 nm. The assay had a sensitivity of 1.6 micrograms/ml and a linearity of up to 600 micrograms/ml and 16 mg/ml in serum and urine, respectively, with only 0.1 ml of sample. The interday and intraday coefficients of variation for replicate analyses of spiked serum and urine specimens were less than 6.5%. PMID:6517560

Activity of amikacin against Mycobacterium avium complex under simulated in vivo conditions.

PubMed Central

Gangadharam, P R; Kesavalu, L; Rao, P N; Perumal, V K; Iseman, M D

1988-01-01

We studied the activity of amikacin against Mycobacterium avium complex strain 101 by using continuous-level, changing concentrations which simulated levels in serum in a patient, and pulsed exposures. Amikacin at a concentration of 5 or 15 micrograms/ml showed rapid bactericidal action following constant exposure of the organisms. With the in vitro model, using a peak concentration of 10 or 20 micrograms/ml, complete sterilization was obtained by day 7. In pulsed-exposure studies, a minimum period of contact of 72 or 96 h at a concentration of 10 micrograms/ml was needed for complete sterilization. PMID:3415209

Improved procedure for determination of flucytosine in human blood plasma by high-pressure liquid chromatography.

PubMed Central

Schwertschlag, U; Nakata, L M; Gal, J

1984-01-01

Several high-pressure liquid chromatography procedures for the determination of flucytosine in serum or plasma have appeared. Some of these suffer from significant disadvantages, and none was applicable in our routine clinical therapeutic-drug-monitoring laboratory. A new high-pressure liquid chromatography assay for flucytosine was therefore developed. A 100-microliter sample of plasma was treated with an aqueous 5-iodocytosine internal-standard solution, and the mixture was deproteinized with trichloroacetic acid. A portion of the protein-free supernatant was diluted with 0.1 M ammonium phosphate, and an aliquot of the resulting solution was injected into the high-pressure liquid chromatography system. Chromatography was performed on a strong-cation-exchange column with a mobile phase containing aqueous ammonium phosphate, phosphoric acid, methanol, and acetonitrile. Detection was at 254 nm. The assay was shown to be linear in the 10 to 200-micrograms/ml drug-concentration range. Forty other drugs were tested for potential interference with the assay, and none was found. For routine use, a single-point working standard containing 75 micrograms of flucytosine per ml was used, giving intraassay coefficients of variation at 50 and 150 micrograms/ml of 1.8 and 2.3% respectively, whereas the day-to-day coefficient of variation at 50 micrograms/ml was 10.0%. Advantages of the procedure include the small sample size, the use of a convenient and reliable internal standard, speed, and simplicity. The assay is highly suitable for routine clinical drug-analysis laboratories. PMID:6508261

Plants transformed with a tobacco mosaic virus nonstructural gene sequence are resistant to the virus.

PubMed Central

Golemboski, D B; Lomonossoff, G P; Zaitlin, M

1990-01-01

Nicotiana tabacum cv. Xanthi nn plants were transformed with nucleotides 3472-4916 of tobacco mosaic virus (TMV) strain U1. This sequence contains all but the three 3 terminal nucleotides of the TMV 54-kDa gene, which encodes a putative component of the replicase complex. These plants were resistant to infection when challenged with either TMV U1 virions or TMV U1 RNA at concentrations of up to 500 micrograms/ml or 300 micrograms/ml, respectively, the highest concentrations tested. Resistance was also exhibited when plants were inoculated at 100 micrograms/ml with the closely related TMV mutant YSI/1 but was not shown in plants challenged at the same concentrations with the more distantly related TMV strains U2 or L or cucumber mosaic virus. Although the copy number of the 54-kDa gene sequence varied in individual transformants from 1 to approximately 5, the level of resistance in plants was not dependent on the number of copies of the 54-kDa gene sequence integrated. The transformed plants accumulated a 54-kDa gene sequence-specific RNA transcript of the expected size, but no protein product was detected. Images PMID:2385595

Effects of three oxidizing biocides on Legionella pneumophila serogroup 1.

PubMed Central

Domingue, E L; Tyndall, R L; Mayberry, W R; Pancorbo, O C

1988-01-01

A study was conducted to determine the bactericidal effects of ozone and hydrogen peroxide relative to that of free chlorine on Legionella pneumophila serogroup 1. In laboratory batch-type experiments, organisms seeded at various densities were exposed to different concentrations of these biocides in demand-free buffers. Bactericidal effects were measured by determining the ability of L. pneumophila to grow on buffered charcoal-yeast extract agar supplemented with alpha-ketoglutarate. Ozone was the most potent of the three biocides, with a greater than 99% kill of L. pneumophila occurring during a 5-min exposure to 0.10 to 0.30 micrograms of O3 per ml. The bactericidal action of O3 was not markedly affected by changes in pH or temperature. Concentrations of 0.30 and 0.40 micrograms of free chlorine per ml killed 99% of the L. pneumophila after 30- and 5-min exposures, respectively. A 30-min exposure to 1,000 micrograms of H2O2 per ml was required to effect a 99% reduction of the viable L. pneumophila population. However, no viable L. pneumophila could be detected after a 24-h exposure to 100 or 300 micrograms of H2O2 per ml. Attempts were made to correlate the biocidal effects of O3 and H2O2 with the oxidation of L. pneumophila fatty acids. These tests indicated that certain biocidal concentrations of O3 and H2O2 resulted in a loss or severe reduction of L. pneumophila unsaturated fatty acids. PMID:3377492

Isometachromin, a new cytotoxic sesquiterpenoid from a deep water sponge of the family Spongiidae.

PubMed

McConnell, O J; Longley, R; Gunasekera, M

1992-09-15

Isometachromin (1), a new sesquiterpene-quinone that is related structurally to metachromin C (2), and the known compounds ilimaquinone (3) and 5-epi-ilimaquinone (4), were isolated from a deep water sponge in the family Spongiidae; the structure of isometachromin was elucidated by spectral methods. Isometachromin exhibits in vitro cytotoxicity against the human lung cancer cell line A549 (IC50 = 2.6 micrograms/ml), but not against P388 murine leukemia (IC 50 > or equal to 10 micrograms/ml) and also exhibits antimicrobial activity.

[Effect of beta-ecdysterone in competitive cultures of Drosophila melanogaster].

PubMed

Botella, L M; Ménsua, J L

1987-03-01

High levels of beta-ecdysterone (more than 1 microgram/ml) have been shown to decrease larva-adult viability and to speed up developmental times when supplied to the media in crowding cultures. The highest doses (100 micrograms/ml) of ecdysterone suppresses almost completely the phenomenon of larval stop in the third instar of development, first reported by our laboratory in overcrowded situations. Thus, one may deduce that stopped larvae could have low levels of ecdysone, and perhaps these are the ultimate physiological cause of their arrested development before the critical larva-pupa molt.

Thin layer chromatography of p-aminophenol in urine after mixed exposure to aniline and toluene.

PubMed Central

Bieniek, G; Karmańska, K; Wilczok, T

1984-01-01

A simple method of evaluating p-aminophenol in the urine of people exposed simultaneously to aniline and toluene relies on separating p-aminophenol from hippuric acid and other physiological components of the urine by thin layer chromatography. The adsorbents and developing system have been thus fixed to make possible the separation of p-aminophenol from hippuric acid, urea, and creatinine and their quantitative determination. This method also makes possible the determination of p-aminophenol in urine in the presence of hippuric acid. Hippuric acid is a physiological component of urine and also the metabolite of toluene, so the determination of p-aminophenol is possible also after simultaneous exposure to both compounds: aniline and toluene. At the same time the concentrations of urea and creatinine as additional factors may be determined. The limit of detection of the method is: 5 micrograms/ml for p-aminophenol, 9 micrograms/ml for hippuric acid, 8 micrograms/ml for urea, and 6 micrograms/ml for creatinine. PMID:6722055

The effect of phenformin on insulin-stimulated isoaminobutyric acid (AIB) transport by isolated hepatocytes.

PubMed Central

Woods, R. J.; Dandona, P.

1984-01-01

Hepatocytes isolated from adult rat livers by collagenase perfusion were used to investigate the effect of phenformin on amino acid transport by measuring the uptake of aminoisobutyric acid (AIB). At concentrations between 0.01 and 100 micrograms/ml, phenformin hydrochloride did not affect AIB uptake, but concentrations of 500 and 1000 micrograms/ml were inhibitory. Incubating hepatocytes with insulin increased their accumulation of AIB. Inclusion of up to 100 micrograms/ml, phenformin hydrochloride during maximal and submaximal stimulation by insulin did not affect AIB uptake, but inhibition occurred with 500 and 1000 micrograms/ml. The continued presence of phenformin after addition of AIB was not required in order to produce inhibition. Furthermore, increasing the duration of exposure of hepatocytes to phenformin increased the degree of inhibition, suggesting that it is a non-competitive inhibitor. We conclude that phenformin does not enhance the sensitivity of hepatocytes to insulin and that at higher concentrations it may exert an inhibitory effect on basal and insulin stimulated aminoacid transport. PMID:6370292

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

PubMed Central

Fletcher, G G; Rossetto, F E; Turnbull, J D; Nieboer, E

1994-01-01

Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 micrograms Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 micrograms Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of approximately 1:1.5 to 1:5 (except approximately 1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Ni]); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. PMID:7843140

Biocompatability of hydroxyapatite composite as a local drug delivery system.

PubMed

Krisanapiboon, A; Buranapanitkit, B; Oungbho, K

2006-12-01

To investigate the biocompatibility of hydroxyapatite composite (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin, fosfomycin, imipenem, or amphotericin B. The interactions of the extract from each drug against osteoblast were tested using the methylthiotetrazole test. Extracts from all drugs showed good biocompatibility at concentrations varying from 10 microgram/ml to 1000 microgram/ml. Imipenem and amphotericin B at a concentration of 1000 microgram/ml had a significantly higher percentage of cell viability than the control group. No morphological change of osteoblast was observed in all drug tests at any concentrations. The hydroxyapatite composite had a good biocompatibility for carrying gentamicin, fosfomycin, imipenem, or amphotericin B.

Microwave-assisted extraction and a new determination method for total steroid saponins from Dioscorea zingiberensis C.H. Wright.

PubMed

Ren, Yao; Chen, Yu; Hu, Bohan; Wu, Hui; Lai, Furao; Li, Xiaofeng

2015-12-01

An efficient microwave-assisted extraction (MAE) technique was applied to isolate total steroid saponins from Dioscorea zingiberensis C.H. Wright (DZW). The optimal extracting conditions were established as 75% ethanol as solvent, ratio of solid/liquid 1:20 (g/ml), temperature 75 °C, irradiation power 600 W and three extraction cycles of 6 min each. Scanning electron microscopy (SEM) images of DZW processed by four different extractions provided visual evidence of the disruption effect on DZW. Diosgenin was quantified by HPLC and examined further by LC-ESI/MS after acid hydrolysis. Total steroid saponins were calculated using diosgenin from total steroid saponins. The MAE procedure was optimized, validated and compared with other conventional extraction processes. This report provides a convenient technology for the extraction and quantification of total saponins of DZW combining MAE with HPLC and LC-ESI/MS for the first time. Copyright © 2015 Elsevier Inc. All rights reserved.

A cytotoxic substance from Sangre de Grado.

PubMed

Itokawa, H; Ichihara, Y; Mochizuki, M; Enomori, T; Morita, H; Shirota, O; Inamatsu, M; Takeya, K

1991-04-01

Taspine has been isolated as a cytotoxic substance from Sangre de Grado, sap of Croton palanostigma (Euphorbiaceae), by bioassay guided fractionation. The cytotoxicity (IC50) of taspine was found to be 0.39 microgram/ml against KB cells and 0.17 microgram/ml against V-79 cells.

Leishmanicidal activity of saponins isolated from the leaves of Eclipta prostrata and Gymnema sylvestre

PubMed Central

Khanna, Venkatesan Gopiesh; Kannabiran, Krishnan; Getti, Giulia

2009-01-01

Objective: To evaluate the leishmanicidal activity of saponin, dasyscyphin C of Eclipta prostrata and sapogenin, gymnemagenol from Gymnema sylvestre leaves under in vitro conditions. Materials and Methods: Dasyscyphin C/Gymnemagenol were dissolved in phosphate buffered saline (PBS) and diluted with liquid medium to obtain concentrations ranging from 1000 to 15 μg /ml. The leishmanicidal activity against leishmanial parasites, Leishmania major, Leishmania aethiopica and Leishmania tropica promastigotes was studied by the MTS assay. Result: The Dasyscyphin C isolated from E. prostrata showed good leishmanicidal activity at 1000μg/ml concentration, with the IC50 value of 450μg/ml against L. major promastigote and the percentage of parasitic death was 73; whereas, gymnemagenol of G. sylvestre showed only 52% parasitic death at 1000 μg/ml concentration. The other Leishmania species, L. aethiopica and L. tropica promastigotes, were less sensitive to the saponins of E. prostrata and G. sylvestre. Conclusion: From this study, it can be concluded that the dasyscyphin C of E. prostrata has significant leishmanicidal activity against L. major promastigote. PMID:20177579

Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period.

PubMed

Lovering, E G; Matsui, F; Curran, N M; Robertson, D L; Sears, R W

1983-08-01

Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 micrograms/ml over a 23-month period. Isoniazid tablets are also stable, but hydrazine levels in an elixir and a pyridoxine combination product doubled to 44 micrograms/ml and 19 micrograms/tablet, respectively. Levels in phenelzine tablets appeared to remain constant at approximately 60 micrograms/tablet, with considerable tablet-to-tablet variation.

Phenolic contents, antioxidant and anticholinesterase potentials of crude extract, subsequent fractions and crude saponins from Polygonum hydropiper L

PubMed Central

2014-01-01

Background We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic contents, antioxidant, anticholinesterase activities, in an attempt to rationalize its use in neurological disorders. Methods Plant crude extract (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential. Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay. Moreover, total phenolic contents of plant extracts were determined and expressed in mg of gallic acid equivalent per gram of dry sample (mg GAE/g dry weight). Results Among different fractions, Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited high phenolic contents. All fractions showed concentration dependent DPPH scavenging activity, with Ph.EtAc 71.33% (IC50 15 μg/ml), Ph.Bt 71.40% (IC50 3 μg/ml) and Ph.Sp 71.40% (IC50 35 μg/ml) were most potent. The plant extracts exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%), Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50 < 0.01 μg/ml. All fractions showed moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 μg/ml), Ph.Hex, 87.49% (IC50 35 μg/ml), Ph.Chf, 84.76% (IC50 55 μg/ml), Ph.Sp, 87.58% (IC50 108 μg/ml) and Ph.EtAc 79.95% (IC50 310 μg/ml) at 1 mg/ml). Furthermore the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40 μg/ml), Ph.Chf 85.94% (IC50 215 μg/ml), Ph.Aq 87.62% (IC50 3 μg/ml) and Ph.EtAc 81.01% (IC50 395 μg/ml) fractions. Conclusions In this study, for the first time, we determined phenolic contents, isolated crude saponins, investigated antioxidant and anticholinestrase potential of P. hydropiper extracts. The results indicate that P. hydropiper is enriched with potent bioactive compounds and warrant further investigation by isolation and structural elucidation to find novel and affordable compounds for the treatment of various neurological disorders. PMID:24884823

Phenolic contents, antioxidant and anticholinesterase potentials of crude extract, subsequent fractions and crude saponins from Polygonum hydropiper L.

PubMed

Ayaz, Muhammad; Junaid, Muhammad; Ahmed, Jawad; Ullah, Farhat; Sadiq, Abdul; Ahmad, Sajjad; Imran, Muhammad

2014-05-03

We investigated Polygonum hydropiper L. (P. hydropiper) for phenolic contents, antioxidant, anticholinesterase activities, in an attempt to rationalize its use in neurological disorders. Plant crude extract (Ph.Cr), its subsequent fractions: n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) free radical scavenging potential. Further, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay. Moreover, total phenolic contents of plant extracts were determined and expressed in mg of gallic acid equivalent per gram of dry sample (mg GAE/g dry weight). Among different fractions, Ph.Cr (90.82), Ph.Chf (178.16), Ph.EtAc (203.44) and Ph.Bt (153.61) exhibited high phenolic contents. All fractions showed concentration dependent DPPH scavenging activity, with Ph.EtAc 71.33% (IC50 15 μg/ml), Ph.Bt 71.40% (IC50 3 μg/ml) and Ph.Sp 71.40% (IC50 35 μg/ml) were most potent. The plant extracts exhibited high ABTS scavenging ability i.e. Ph.Bt (91.03%), Ph.EtAc (90.56%), Ph.Sp (90.84%), Ph.Aq (90.56%) with IC50<0.01 μg/ml. All fractions showed moderate to high AChE inhibitory activity as; Ph.Cr, 86.87% (IC50 330 μg/ml), Ph.Hex, 87.49% (IC50 35 μg/ml), Ph.Chf, 84.76% (IC50 55 μg/ml), Ph.Sp, 87.58% (IC50 108 μg/ml) and Ph.EtAc 79.95% (IC50 310 μg/ml) at 1 mg/ml). Furthermore the BChE inhibitory activity was most prominent in Ph.Hex 90.30% (IC50 40 μg/ml), Ph.Chf 85.94% (IC50 215 μg/ml), Ph.Aq 87.62% (IC50 3 μg/ml) and Ph.EtAc 81.01% (IC50 395 μg/ml) fractions. In this study, for the first time, we determined phenolic contents, isolated crude saponins, investigated antioxidant and anticholinestrase potential of P. hydropiper extracts. The results indicate that P. hydropiper is enriched with potent bioactive compounds and warrant further investigation by isolation and structural elucidation to find novel and affordable compounds for the treatment of various neurological disorders.

[Clinical study of BRL 25000 (clavulanic acid-amoxicillin) granules in pediatric infections].

PubMed

Nagamatsu, I; Horiguchi, S; Hatae, T

1985-02-01

BRL 25000 granules, a formulation of amoxicillin (AMPC) and the beta-lactamase inhibitor clavulanic acid (CVA) in a ratio of 2 to 1, was studied clinically and bacteriologically in pediatric infections. The in vitro antibacterial activity of BRL 25000 was superior to AMPC against beta-lactamase producing strains. The pharmacokinetics of the BRL 25000 granule were studied following oral administration to a 6 years old female and 9 years old male in the fasting state at dose levels of 10 mg/kg and 16.1 mg/kg, respectively. In the case of the female dosed at 10 mg/kg, the peak serum concentrations were found to be 6.38 micrograms/ml for AMPC and 1.83 micrograms/ml for CVA at 1 hour following administration. The elimination half-life of AMPC was 0.86 hour and that of CVA was 0.67 hour. The 4-hour urinary recovery was 61.89% for AMPC and 17.92% for CVA. In the male receiving 16.1 mg/kg, the peak concentrations were 2.55 micrograms/ml for AMPC at 3 hours following administration and 1.46 micrograms/ml for CVA at 1.5 hours following administration. The elimination half-life of AMPC was 1.59 hours and that of CVA was 1.19 hours. The 6-hour urinary recovery was 44.19% for AMPC and 30.05% for CVA. In clinical studies, the BRL 25000 granule was administered to 36 infants with upper respiratory tract infections, mainly tonsillitis, urinary tract infections etc. Good clinical efficacy was obtained in 33/36 cases (91.7%). Diarrhea and rash were occasionally noted side effects but were not severe. From the above results, it can be concluded that the BRL 25000 granule is a suitable and effective drug for use in the treatment of pediatric infections.

Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

PubMed

Giustina, A; Bussi, A R; Legati, F; Bossoni, S; Licini, M; Schettino, M; Zuccato, F; Wehrenberg, W B

1992-12-01

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p < 0.05). GH peaks after GHRH+galanin were also significantly lower in hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p < 0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

PubMed Central

Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

2012-01-01

Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

Putative mechanism for apoptosis-inducing properties of crude saponin isolated from sea cucumber (Holothuria leucospilota) as an antioxidant compound

PubMed Central

Soltani, Mozhgan; Parivar, Kazem; Baharara, Javad; Kerachian, Mohammad Amin; Asili, Javad

2015-01-01

Objective(s): Marine organisms are known as a potential source of natural products, which contain bioactive substances with therapeutic properties. Sea cucumbers are prominent among marine organisms because of their dietary and therapeutic applications. In addition, they have capacity of synthesizing saponins molecules and other metabolites with therapeutic properties such as antitumor, antimicrobial, anti-inflammatory and antioxidant activities. The aim of this study was to evaluate the antioxidant and pro-apoptotic effects of sea cucumber saponins (SCS) isolated from Holothuria leucospilota species. Materials and Methods: Evaluation of antioxidant activity of SCS was carried out by DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS (azino-bis-3-ethylbenzothiazoline-6-sulfonic acid), power reducing and total antioxidant assays. The anti-proliferative effect was studied by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Mechanisms leading to apoptosis were also evaluated by fluorescence microscopy, flow cytometry and real time PCR. Results: The results showed that the DPPH and ABTS activities increased in a dose dependent manner. The reducing capacity enhanced with increasing concentration of the saponin extract (0 to 2 mg/ml). The SCS exhibited moderate total antioxidant activity. Evaluation of anti-proliferative effect revealed that SCS with IC50 of about 6 μg/ml, can display a good cytotoxic activity in a dose dependent manner. Further apoptosis induction was confirmed by fluorescence microscopy and flow cytometry. Sea cucumber saponin was also found to exert a pro-apoptotic effect by increasing the expression of Bax and decreasing the expression of Bcl2. Conclusion: These results indicate that the SCS may act as a natural antioxidant and antitumor agent. PMID:25810893

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery.

PubMed Central

Bergeron, M G; Saginur, R; Desaulniers, D; Trottier, S; Goldstein, W; Foucault, P; Lessard, C

1990-01-01

The concentrations of teicoplanin in sera and heart tissues of 49 patients undergoing coronary bypass were measured. Each patient received a 6- or 12-mg/kg dose of teicoplanin administered in a slow intravenous bolus injection over 3 to 5 min beginning at the time of induction of anesthesia. Mean +/- standard error of the mean concentrations in serum were, for the two doses, respectively, 58.1 +/- 1.7 and 123.3 +/- 7.4 micrograms/ml 5 min after administration and 22.2 +/- 0.7 and 56.5 +/- 2.8 micrograms/ml at the time of removal of atrial appendages. Mean +/- standard error of the mean concentrations in tissue were 70.6 +/- 1.7 and 139.8 +/- 2.2 micrograms/g, respectively, giving mean tissue/serum ratios of 3.7 +/- 0.3 and 2.8 +/- 0.2, respectively. Teicoplanin penetrates heart tissue readily and reaches levels in the serum far in excess of the MICs for most pathogens that have been found to cause infections following open heart surgery. PMID:2149493

Orally administered ketoconazole: route of delivery to the human stratum corneum.

PubMed Central

Harris, R; Jones, H E; Artis, W M

1983-01-01

Delivery of ketoconazole to human stratum corneum was studied. Thirteen healthy volunteers, three patients with chronic fungal disease and one patient with palmar-plantar hyperhidrosis were given 400 mg of ketoconazole daily for various lengths of time. The ketoconazole content of palmar stratum corneum, eccrine sweat, sebum, and serum was measured by high-pressure liquid chromatography (sensitivity, 0.005 to 0.010 microgram/ml). Palmar stratum corneum obtained after 7 and 14 days of daily administration contained up to 14 micrograms of ketoconazole per g. Ketoconazole was not found in sebum after 7 or 14 days of daily ingestion of the antimycotic agent. Sebum from three patients with chronic fungal infection treated for greater than 9 months contained ketoconazole (means, 4.7 micrograms/g). Thermogenic whole body eccrine sweat contained a mean of 0.059 microgram/ml on day 7 and 0.084 microgram/ml on day 14 of daily administration. Ketoconazole appeared in thermogenic whole body eccrine sweat and palmar hyperhidrotic sweat within 1 h after a single oral dose. Partition studies of ketoconazole containing eccrine sweat demonstrated a 10-fold greater concentration in the sediment phase (desquamated keratinocytes) compared with the clear supernatant phase. In vitro studies with [3H]ketoconazole-supplemented supernatant sweat revealed preferential binding to stratum corneum, hair, and nails and its partitioning to lipid-rich sebum. We conclude that eccrine sweat rapidly transports ketoconazole across the blood-skin barrier, where it may bind or partition to keratinocytes and surface lipids. PMID:6318663

The iothalamate clearance in cats with experimentally induced renal failure.

PubMed

Ohashi, F; Kuroda, K; Shimada, T; Shimada, Y; Ota, M

1996-08-01

Plasma iothalamate (IOT) disappearance rates were measured after a single-injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal failure. The disappearance rates especially fitted into the one compartment model. The mean value of plasma disappearance rates of IOT in these cats with induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3) micrograms/ml/min). These results demonstrate that IOT clearance is available for evaluation of renal function in cats.

In vitro activity and beta-lactamase stability of a new difluoro oxacephem, 6315-S.

PubMed Central

Neu, H C; Chin, N X

1986-01-01

6315-S, a novel difluoromethyl thioacetamido oxacephem, had in vitro activity comparable to that of cefotaxime and moxalactam against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Citrobacter diversus, Salmonella spp., and Shigella spp., inhibiting 90% at less than or equal to 0.25 microgram/ml. It inhibited piperacillin- and cefoperazone-resistant isolates in these species. 6315-S did not inhibit cefotaxime- or moxalactam-resistant Citrobacter freundii, Enterobacter aerogenes, or Enterobacter cloacae (MICs for 90% of the strains tested were greater than or equal to 16 micrograms/ml). Proteus vulgaris resistant to cefotaxime was inhibited. Pseudomonas species and Acinetobacter species were resistant (MICs greater than 64 micrograms/ml). MICs for 90% of the Staphylococcus aureus and S. epidermidis isolates were 4 micrograms/ml. 6315-S was highly active against anaerobic species of Clostridium, Fusobacterium, Bacteroides, and peptostreptococci and was superior to other agents against these organisms. 6315-S was not hydrolyzed by the major plasmid and chromosomal beta-lactamases, but it induced chromosomal beta-lactamases in Enterobacter cloacae and Pseudomonas aeruginosa. PMID:3492172

Vitamin E in cranes: reference ranges and nutrient interactions

USGS Publications Warehouse

Dierenfeld, Ellen S.; Sheppard, C.D.; Langenberg, J.; Mirande, C.; Spratt, J.; Dein, F.J.

1993-01-01

Fat soluble vitamins E and A (quantified as alpha-tocopherol and all-trans retinol, respectively) were measured in plasma samples from 274 captive cranes from four institutions and five free-ranging birds. Ages ranged from 4 mo to 80 yr, and all 15 crane species were represented. Captive cranes had a mean +/- standard error (SE) of 6.57 +/- 0.82 micrograms/ml alpha-tocopherol; migrating greater sandhill cranes (Grus canadenis tabida) had a plasma concentration of 3.71 +/- 0.22 micrograms/ml. Sex and age differences were not significant, but crane species that evolved in temperate habitats had higher circulating levels of alpha-tocopherol than tropical or subtropical species. Mean +/- SE retinol values were 0.69 +/- 0.05 micrograms/ml in captive cranes, and 0.66 +/- 0.08 micrograms/ml in free-ranging cranes; values did not differ significantly by sex, age, or species. Dietary vitamin E concentrations were significantly correlated with plasma alpha-tocopherol levels in a logarithmic relationship. Dietary selenium at 0.5 mg/kg was associated with decreased circulating alpha-tocopherol concentrations.

Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism.

PubMed

Giustina, A; Buffoli, M G; Bussi, A R; Wehrenberg, W B

1991-01-01

Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of basic fibroblast growth factor in suramin-induced inhibition of V79/AP4 fibroblast cell proliferation.

PubMed Central

Bernardini, N.; Giannessi, F.; Bianchi, F.; Dolfi, A.; Lupetti, M.; Citti, L.; Danesi, R.; Del Tacca, M.

1993-01-01

The V79/AP4 Chinese hamster fibroblasts were densely stained with the anti-basic fibroblast growth factor (bFGF) antibody demonstrating an endogenous production of the peptide. The in vitro proliferation of these cells was stimulated by exogenous bFGF and the maximum growth (259% increase in 3H-thymidine incorporation into DNA) was reached with bFGF 10 ng ml-1. Inhibition of bFGF-mediated mitogenic pathway was obtained with a 15-mer antisense oligodeoxynucleotide targeted against bFGF mRNA and with suramin, a drug which blocks the biological activity of heparin-binding growth factors. bFGF antisense oligomer reduced the synthesis of DNA by 79.5 and 89.5% at 20 and 60 microM, respectively; this effect was reversed by the addition of exogenous bFGF to the culture medium. A short-term exposure to suramin 300 micrograms ml-1 produced a modest reduction in 3H-thymidine incorporation but suppressed the mitogenic effect of bFGF on V79/AP4 cells. In cells treated with suramin 300 micrograms ml-1 the drug concentration increased linearly over 3 days, reaching 13.15 micrograms mg-1 of protein; cell proliferation was inhibited in a dose-related manner as evaluated by the colony formation assay (IC50: 344.22 micrograms ml-1) and by the number of mitoses observed in culture. Furthermore, the drug induced ultrastructural alterations, consisting of perinuclear cisternae swelling, chromatin condensation, nucleolar segregation and cytoplasmic vacuolations. These findings demonstrated that the endogenous production of bFGF plays an important role in V79/AP4 fibroblasts proliferation, and the inhibition of bFGF-mediated mitogenic signalling with bFGF antisense oligomer or suramin is an effective mean of reducing cell growth. Images Figure 1 Figure 5 Figure 6 PMID:7685616

Utilization of dietary urea in rainbow trout.

PubMed

Kaushik, S J; Dabrowski, K R; Dabrowska, H; Olah, E; Luquet, P

1983-01-01

Experiments were conducted to examine the potential utilization of dietary urea by rainbow trout. A control diet and two diets supplemented with 1 and 3% of urea were fed to fish. Postprandial levels of urea and ammonia in blood plasma, and postprandial excretion of these metabolites were followed during 24 h. Apparent digestibility of urea in rainbow trout was very high (greater than 98%). Maximum values of urea levels in plasma were reached 6 h (32.3 +/- 10.2 micrograms/ml) after a meal in the control fish and respectively 6 h (83.4 +/- 18.4 micrograms/ml) and 8 h (250.3 +/- 96.1 micrograms/ml) after a meal in trout fed 1 and 3% urea diets. Peaks of urea excretion rates appeared 7-9 h after meal, coinciding with the highest circulating urea concentration. Total daily urea excretion amounted to 5.53, 10.43 and 33.80 mg urea N/100 mg N intake in trout fed the control, 1 and 3% urea diets, respectively. It is concluded that the dietary urea is readily absorbed in the digestive tract of trout but is totally excreted thus leading to no beneficial effect on nitrogen balance. This excretion of urea also takes place passively without any increase in energy demands.

A study of the prevalence and clinical significance of venom-specific IgE.

PubMed

Zora, J A; Swanson, M C; Yunginger, J W

1988-01-01

The prevalence of unrecognized Hymenoptera-venom sensitization, assessed by venom skin tests (VSTs) in adults with no history of adverse reactions to sting, has been as high as 12% in previous epidemiologic studies. To assess further the clinical importance of positive VSTs in such individuals, we skin tested 33 subjects stung in the field during the preceding 12 months without reaction, and 33 persons who denied being stung in the preceding 3 years. Among the recently stung group, 12/33 had at least one positive VST (greater than or equal to 2+) at 1.0 microgram/ml, whereas 5/33 had positive VST at 0.1 microgram/ml. In contrast, only 2/33 nonstung subjects had positive VST at 1.0 microgram/ml, and none were positive at 0.1 microgram/ml. To estimate, prospectively, the sensitization rate after insect stings, we studied a third group of 11 nonsensitive patients with negative skin tests to Hymenoptera. After a deliberate in-hospital honeybee sting, only 1/11 developed a persistently positive honeybee VST. From among the three groups, we then performed nine sting challenges in eight patients with positive VSTs, and all stings were tolerated without significant reaction. We also measured IgE antibodies to Hymenoptera venoms in random blood bank donors. During April to May, 2/216 sera contained elevated venom-specific IgE antibodies, whereas 14/201 sera collected from October to November contained elevated venom-specific IgE antibodies. We conclude that a small but appreciable portion of the population has venom-specific IgE antibodies and that the prevalence is seasonably variable. Our data indicate that persons recently stung without significant reaction contribute to this group but that only a small portion of this group is at risk for a systemic reaction with a future sting.

Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery.

PubMed Central

Kager, L; Liljeqvist, L; Malmborg, A S; Nord, C E

1981-01-01

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients. PMID:7325640

Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery.

PubMed

Kager, L; Liljeqvist, L; Malmborg, A S; Nord, C E

1981-12-01

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients.

Role of the DIP Molecules in DCC Signaling

DTIC Science & Technology

1999-09-01

to policies of applicable Federal Law 45 CFR 46. N/A In conducting research utilizing recombinant DNA technology , the investigator(s) adhered to...for 1 h, then with 0.1 mg/ml of proteinase K, 0.1% SDS at 50’C Ihle, 1995; Fraser and Evan, 1996). These molecules overnight. Samples were extracted ...incubated with 20 yg/ml of anti-DCC antibody diluted in PBS-0.1% saponin for 1 h, washed with PBS, blocked Western blotting with 5% normal donkey serum for 1

[Isolation of a strain of M. tuberculosis which is considered to be rifampicin-dependent, from a patient with long-lasted smear positive and culture difficult (SPCD) mycobacteria].

PubMed

Nakamura, M; Harano, Y; Koga, T

1990-09-01

During the course of clinical examination of drug sensitivity tests for M. tuberculosis, a strain of M. tuberculosis which is considered to be rifampicin-dependent was isolated from a patient with persisting smear positive, culture negative (SPCN) or culture difficult (SPCD) mycobacteria status. The strain isolated produced a few tiny colonies on the control Ogawa-egg yolk medium, whereas it showed abundant growth like a bacteria plaque on the medium containing rifampicin 50 micrograms/ml. Furthermore, the growth of the strain on Ogawa medium containing rifampicin 50 micrograms/ml is much better than that on the medium containing rifampicin 10 micrograms/ml.

Effects of inositol trisphosphate on calcium mobilization in high-voltage and saponin-permeabilized platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gear, A.R.L.; Hallam, T.J.

1986-03-01

Interest in phosphatidylinositol metabolism has been greatly stimulated by the findings that diglyceride and inositol phosphates may serve as second messengers in modulating cellular function. Formation of 1,4,5-inositol trisphosphate (IP/sub 3/), in particular, has been linked to mobilization of intracellular calcium in a number of cell types. The authors have examined the ability of IP/sub 3/ to mobilize calcium in human platelets permeabilized by either saponin or high-voltage discharge. Saponin at 15 ..mu..g/ml effectively permeabilized platelets to exogenous inositol 1,4,5-trisphosphate which released bound (/sup 45/Ca) within 1 min and with a Ka of 7.4 +/- 4.1 ..mu..M. A small (25%)more » azide-sensitive pool was also responsive to inositol trisphosphate. The calcium pools were completely discharged by A-23187 and the ATP-dependent uptake was prevented by dinitrophenol. In contrast to the result with saponin, platelets accessed by high-voltage discharge were insensitive to challenge by inositol 1,4,5-trisphosphate. The data suggest that while inositol 1,4,5-trisphosphate can rapidly mobilize platelet calcium, the ability to demonstrate this depends on the method of permeabilization.« less

Antitumor and anti-angiogenic potentials of isolated crude saponins and various fractions of Rumex hastatus D. Don.

PubMed

Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Zeb, Anwar; Ullah, Farman; Sadiq, Abdul

2016-03-12

Cancer, being the foremost challenge of the modern era and the focus of world-class investigators, gargantuan research is in progress worldwide to explore novel therapeutic for its management. The exploitation of natural sources has been proven to be an excellent approach to treat or minify the excessive angiogenesis and proliferation of cells. Similarly, based the ethnomedicinal uses and literature survey, the current study is designed to explore the anti-tumor and anti-angiogenic potentials of Rumex hastatus. Anti-tumor and anti-angiogenic activities were carried out using potato-disc model and chorioallantoic membrane (CAM) assay respectively. Moreover, R. hastatus was also assessed for antibacterial activity against Agrobacterium tumefaciens (tumor causing bacterial strain). The positive controls used in anti-tumor, anti-angiogenic and antibacterial activities were vincristine sulphate, dexamethasone and cefotaxime respectively. The crude saponins (Rh.Sp), methanolic extract (Rh.Cr) and other solvent extracts like n-hexane (Rh.Hex), chloroform (Rh.Chf), ethylacetate (Rh.EtAc) and aqueous fraction (Rh.Aq) exhibited notable anti-tumor and anti-angiogenic activities. In potato tumor assay, the chloroform and saponin fractions were observed to be the most effective showing 86.7 and 93.3 % tumor inhibition at 1000 µg/ml with IC50 values 31.6 and 18.1 µg/ml respectively. Similarly, these two samples i.e., chloroform and saponins also excelled among the entire test samples in anti-angiogenic evaluation exhibiting 81.6 % (IC50 = 17.9 µg/ml) and 78.9 % (IC50 = 64.9 µg/ml) at 1000 µg/ml respectively. In contrast, the antibacterial investigations revealed a negligible potential against A. tumefaciens. Based on our results we can claim that R. hastatus possesses both anti-tumor and anti-angiogenic potentials. In all of the solvent fractions, Rh.Chf and Rh.Sp were most effective against tumor and angiogenesis while having negligible activity against A. tumefaciens. It can be concluded that Rh.Chf and Rh.Sp might be potential targets in the isolation of natural product having anti-neoplastic action.

Adaptations of the Saker-Solomons test: simple, reliable colorimetric field assays for chloroquine and its metabolites in urine.

PubMed

Mount, D L; Nahlen, B L; Patchen, L C; Churchill, F C

1989-01-01

Two field-adapted colorimetric methods for measuring the antimalarial drug chloroquine in urine are described. Both are modifications of the method of Saker and Solomons for screening urine for phencyclidine and other drugs of abuse, using the colour reagent tetrabromophenolphthalein ethyl ester. One method is semiquantitative, detecting the presence of chloroquine (Cq) and its metabolites in urine with a 1 microgram/ml detection limit; it is more sensitive and reliable than the commonly used Dill-Glazko method and is as easy to apply in the field. The second method uses a hand-held, battery-operated filter photometer to quantify Cq and its metabolites with a 2 microgram/ml detection limit and a linear range up to 8 micrograms/ml. The first method was validated in the field using a published quantitative colorimetric method and samples from a malaria study in Nigeria. The second method was validated in the laboratory against high-performance liquid chromatographic results on paired samples from the Nigerian study. Both methods may be used in remote locations where malaria is endemic and no electricity is available.

Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography.

PubMed Central

Rex, J H; Hanson, L H; Amantea, M A; Stevens, D A; Bennett, J E

1991-01-01

An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (less than 2.5% for HPLC versus less than 11% for bioassay) and a lower between-run coefficient of variation (less than 5% versus less than 12% for bioassay) and was more sensitive (lower limit of detection, 0.1 micrograms/ml [versus 2 micrograms/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. PMID:1854166

Lead in human blood and milk from nursing women living near a smelter in Mexico City.

PubMed

Namihira, D; Saldivar, L; Pustilnik, N; Carreón, G J; Salinas, M E

1993-03-01

Lead levels in breast milk and blood were determined in women living within a 200-m radius of 3 smelters in Mexico City. All samples were analyzed on a Perkin Elmer 460 atomic absorption spectrometer equipped with HGA 2200. The mean blood lead level was 45.88 micrograms/dl (SD 19.88 microgram/dl), and the geometric mean of milk lead level was 2.47 micrograms/100 ml. The correlation coefficient of these two variables was 0.88. Using the mean value of lead found in breast milk, an infant of 5.5 kg would ingest 8.1 micrograms/kg/d in his diet. The daily permissible intake (DPI) established by the World Health Organization (WHO) in 1972 for an adult is 5.0 micrograms/kg/d.

[Aldicarb poisoning: review of cases in the North of France between 1998 and 2001].

PubMed

Nisse, P; Deveaux, M; Tellart, A S; Dherbecourt, V; Peucelle, D; Mathieu-Nolf, M

2002-01-01

Among the 2,726 cases of human pesticide poisoning collected at the Poison Centre of Lille from January 1998 to May 2001, 39 cases were related to the ingestion of aldicarb. Analysis of the circumstances found a suicide attempts in 33 cases and an accidental ingestion in 6 cases. The sex-ratio was 31 men for 8 women, mean age was of 36.6 years (15 months--77 years). Thirty one poisoning were symptomatic with muscarinic signs (20 cases), digestive (15 cases), neurological (8 cases), nicotinic signs (6 cases). Treatment was based on digestive evacuation (14 cases), administration of activated charcoal (14 cases), atropine (7 cases), pralidoxime (1 case), preservative vital functions by intubation and ventilation (7 cases). Sedation was necessary in 4 cases. Hospitalization was necessary in 34 cases. The Poison Severity Score was estimated at 0 (any gravity) in 5 cases, 1 (weak) in 12 cases, 2 (moderate) in 7 cases, 3 (severe) in 8 cases and 4 (lethal) in 2 cases. In one of deaths, aldicarb was determined by HPLC-DAD in blood (6.04 micrograms/ml), urines (1.88 micrograms/ml) and gastric contents (3.98 micrograms/ml). These concentrations are the most important ever described in the literature. Aldicarb is the most toxic carbamate insecticide for human.

Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis.

PubMed Central

Kenyon, C J; Fraser, R; Birnie, G G; Connell, J M; Lever, A F

1986-01-01

Isolated bovine adrenocortical cells were incubated with and without 3 ng/ml ACTH, with various concentrations (10-1000 micrograms/ml) of either cimetidine or ranitidine. Cortisol, corticosterone, and deoxycorticosterone outputs were measured. Cimetidine and ranitidine at 320 and 1000 micrograms/ml inhibited ACTH-stimulated corticosterone and cortisol synthesis and cimetidine decreased basal cortisol synthesis. The inhibitory effects of cimetidine on cortisol synthesis were approximately 10 times greater than those of ranitidine. Cimetidine (1000 micrograms/ml), but not ranitidine increased deoxycorticosterone synthesis by ACTH-stimulated cells, indicating inhibition of 11 beta-hydroxylation in the adrenal steroidogenic pathway. Although doses of cimetidine and ranitidine which produce these in vitro effects are much greater than plasma concentrations in normal clinical use, they might be important in acutely ill patients given intravenous bolus injections of cimetidine, or if either antagonist were accumulated by the adrenal to produce high intracellular concentrations. PMID:3023203

Fat soluble vitamins in blood and tissues of free-ranging and captive rhinoceros.

PubMed

Clauss, Marcus; Jessup, David A; Norkus, Edward B; Chen, Tai C; Holick, Michael F; Streich, W Juergen; Dierenfeld, Ellen S

2002-04-01

Several disease syndromes in captive rhinoceroses have been linked to low vitamin status. Blood samples from captive and free-ranging black (Diceros bicornis) and white rhinoceros (Ceratotherium simum) and tissue samples of captive individuals from four rhinoceros species were analysed for vitamins A and E. Circulating vitamin A levels measured as retinol for free-ranging versus captive black and white rhinoceros were 0.04 (+/- 0.03 SD) vs. 0.08 (+/- 0.08) and 0.07 (+/- 0.04) vs. 0.06 (+/- 0.02) microgram/ml, respectively. Circulating vitamin E levels measured as alpha-tocopherol were 0.58 (+/- 0.30) vs. 0.84 (+/- 0.96) and 0.62 (+/- 0.48) vs. 0.77 (+/- 0.32) microgram/ml, respectively. In contrast to earlier findings, there was no significant difference in vitamin E concentration between captive and free-ranging black rhinoceros. When the samples of captive black rhinoceros were grouped into those taken before 1990 and after 1990, however, those collected before 1990 had significantly lower (P < 0.001) vitamin E levels (0.46 +/- 0.83 microgram/ml) and those collected in 1990 or later significantly higher (P < 0.001) vitamin E levels (1.03 +/- 1.04 micrograms/ml) than the captive population as a whole. This is probably due to increased dietary supplementation. There were significant differences in circulating vitamin concentrations in black rhinoceroses from different regions in the wild. Serum 25-hydroxy (OH) vitamin D3 averaged 55.7 ng/ml in free-ranging rhinoceroses; no carotenoids were detected in any blood samples. Captive black and white rhinoceroses appear to be adequately supplemented in vitamin A and E. Captive Indian rhinoceroses (Rhinoceros unicornis) had significantly lower vitamin A concentrations in blood (P < 0.001) and higher vitamin A concentrations in liver tissue samples (P < 0.001) than other rhinoceros species. Equine requirements are not recommended as a model for rhinoceros vitamin requirements.

[Pharmacokinetic and clinical studies of cefmenoxime in neonates and premature infants].

PubMed

Toyonaga, Y; Sugita, M; Kurosu, Y; Hori, M; Seo, K

1989-12-01

Serum concentrations and urinary recovery rates of cefmenoxime (CMX) were determined in 41 mature and premature infants (with ages 0-24 days) after one shot intravenous injection of 10, 20 (1-hour intravenous drip infusion was also carried out) or 30 mg/kg for treatment and prophylaxis of various infections. Because the number of cases included was small, a comparison study was conducted by classifying them into 3 groups; 3 days or younger, 4 to 7 days, and 8 days or older, rather than dividing them into groups of mature and premature infants. Clinical evaluation was conducted in 7 male and 1 female cases 1 to 29 days old, whose diseases comprised 1 case each with septicemia, purulent otitis media and phlegmonous cellulitis, 3 with pneumonia and 2 with urinary tract infection. 1. Changes in serum concentrations and urinary recovery rates (1) Intravenous bolus injection of 10 mg/kg: Serum concentrations of the drug in the 3 age groups peaked at 28.9, 29.5 and 29.1 micrograms/ml, respectively, all at 30 minutes after the drug administration, and thereafter gradually declined. The mean level in the 3rd group was the lowest at 1.9 micrograms/ml at 6 hours. Average serum half-lives of CMX were shorter in older subjects, 3.0, 1.9 and 1.4 hours, respectively in the 3 groups. Urinary recovery rates were relatively high, 68.9 to 84.9% in the 3 cases examined during the first 6 hours, and 15.4 to 66.2% during the first 2 hours. (2) Intravenous bolus injection of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 65.2, 60.5 and 65.8 micrograms/ml, respectively, all at 30 minutes after the drug administration, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups, but remained rather high at 20.1, 6.5 and 9.5 micrograms/ml, respectively, at 6 hours. Average serum half-lives of CMX were 3.5, 1.7 and 1.9 hours, respectively. The inversion of values obtained between the 2nd and 3rd groups appears to be attributable to that all of the 3rd group were premature infants, and the body weight of 2 cases of them were less than 2,000 g each. Urinary recovery rates ranged widely from 37.0 to 89.4% in the 4 cases examined during the first 6 hours. (3) One-hour intravenous drip infusion of 20 mg/kg: Serum concentrations of the drug in the 3 groups peaked at 57.7, 60.2 and 72.4 micrograms/ml, respectively, all at the termination of the drug infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Determination of chondroitin-6-sulphate by a competitive enzyme immunoassay using a biotinylated antigen.

PubMed

Kähnert, H; Brinkmann, T; Gässler, N; Kleesiek, K

1994-04-01

A competitive enzyme immunoassay was developed to determine chondroitin-6-sulphate in body fluids and cell cultures. The assay uses a monoclonal anti-chondroitin-6-sulphate antibody, immobilised to microtitre plates, and it involves a competitive binding reaction between chondroitin-6-sulphate in the samples and the biotinylated antigen. This assay enables the quantification of chondroitin-6-sulphate in the low concentration range of 16-120 micrograms/l. The intra-assay and inter-assay coefficients of variation are below 6.5% and 9.0%, respectively. More than 90% of chondroitin-6-sulphate was recovered when added to 0.1 mol/l phosphate-buffered saline, an albumin solution (40 g/l in phosphate-buffered saline) and cell culture medium (containing 100 ml/l foetal calf serum). Chondroitin-6-sulphate was also determined in sera of healthy male (n = 90) and female (n = 90) blood donors. The normal range was 55-169 micrograms/l. In men the mean value was estimated at 102.2 +/- 37.1 micrograms/l and in women at 98.7 +/- 26.4 micrograms/l. No age or sex dependence was observed. The urine excretion of chondroitin-6-sulphate in men (n = 16) was 44.5 +/- 21.1 mg/kg creatinine (mean +/- standard deviation) and in females (n = 10) 53.5 +/- 21.3 mg/kg creatinine. The clearance rate in men was 0.41 +/- 0.22 ml x min-1 and in women 0.38 +/- 0.15 ml x min-1. No sex dependence was found. Furthermore, the enzyme immunoassay was modified to measure the specific incorporation of a radioactively labelled precursor ([14C]galactosamine) into chondroitin-6-sulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Extraction of saponins and toxicological profile of Teucrium stocksianum boiss extracts collected from District Swat, Pakistan.

PubMed

Shah, Syed Muhammad Mukarram; Sadiq, Abdul; Shah, Syed Muhammad Hassan; Khan, Shahzeb

2014-12-04

The current era is facing challenges in the management of neoplasia and weeds control. The currently available anti-cancer and herbicidal drugs are associated with some serious side effects. Therefore numerous researchers are trying to discover and develop plant based alternative particularly for the rational management of cancer and weed control. Teucrium stocksianum possess antioxidant and analgesic activities. The current study was designed to evaluate crude saponins (CS), methanolic extract and sub-fractions of T. stocksianum for cytotoxic and phytotoxic potentials. CS, methanolic extract and sub-fractions were extracted from powdered plant material using different solvents. Cytotoxic potential of the extracts at a dose of 10, 100 and 1000 μg/ml were evaluated against Brine shrimp's nauplii. Phytotoxic assay also performed at the same concentration against Lemna minor. Etoposide and Paraquat were used as positive controls in cytotoxic and phytotoxic assays respectively. The percent yield of crude saponins was (5%). CS demonstrated tremendous brine shrimp lethality showing < 10 μg/ml LC50. The n-hexane (HF) and chloroform fractions (CF) demonstrated excellent cytotoxicity with 80 and 55 μg/ml LC50 respectively. Whereas the methanolic extract (TSME), ethyl acetate (EAF) and aqueous fractions (AF) revealed moderate cytotoxicity showing 620, 860 and 1000 μg/ml LC50 values respectively. In phytotoxic assay profound inhibition was displayed by HF (96.67%) and TSME (95.56%, 30 μg/ml LC50) against the growth of Lemna minor at 1000 μg/ml respectively. Both CF and EAF demonstrated profound phytoxicity (93.33%) respectively at highest concentration (1000 μg/ml), while AF and CS demonstrated weak phytotoxicity with 1350 and 710 μg/ml LC50 values respectively. Cytotoxicity and phytotoxicity assays indicated that the crude saponins, n-hexane and chloroform fractions of T. stocksianum could play a vital role in the treatment of neoplasia and as potential natural herbicides. Therefore these sub-fractions are recommended for further investigation with the aim to isolate novel anti-cancer and herbicidal compounds.

Intravitreal flomoxef sodium in rabbits.

PubMed

Mochizuki, K; Torisaki, M; Yamashita, Y; Komatsu, M; Tanahashi, T

1993-01-01

We studied the intraocular concentration of flomoxef sodium in nonvitrectomized and vitrectomized eyes of albino rabbits after intravenous administration of 100 mg/kg flomoxef sodium. The concentration of flomoxef sodium in the vitreous body was undetectable (< 0.1 micrograms/ml) in nonvitrectomized eyes. Retinal toxicity of flomoxef sodium was investigated with ophthalmoscopy, electroretinography (ERG) and light microscopy after intravitreal injection of 200, 500, 1,000 and 2,000 micrograms flomoxef sodium in albino and pigmented rabbits. No ERG changes were induced with 200 micrograms. Other higher doses caused transient ERG changes. After the 200-micrograms injection, the intravitreal concentration decreased exponentially, the half-life being 4.4 h. The antibacterial activity, broad coverage and low intravitreal toxicity of flomoxef sodium suggest that this compound may be used to treat bacterial endophthalmitis.

Antiparasitic activity of diallyl trisulfide (Dasuansu) on human and animal pathogenic protozoa (Trypanosoma sp., Entamoeba histolytica and Giardia lamblia) in vitro.

PubMed

Lun, Z R; Burri, C; Menzinger, M; Kaminsky, R

1994-03-01

Garlic (Allium sativum L.) and one of its major components, allicin, have been known to have antibacterial and antifungal activity for a long time. Diallyl trisulfide is a chemically stable final transformation product of allicin which was synthesized in 1981 in China and used for treatment of bacterial, fungal and parasitic infections in man. The activity of diallyl trisulfide was investigated in several important protozoan parasites in vitro. The IC50 (concentration which inhibits metabolism or growth of parasites by 50%) for Trypanosoma brucei brucei, T.b. rhodesiense, T.b. gambiense, T. evansi, T. congolense and T. equiperdum was in the range of 0.8-5.5 micrograms/ml. IC50 values were 59 micrograms/ml for Entamoeba histolytica and 14 micrograms/ml for Giardia lamblia. The cytotoxicity of the compound was evaluated on two fibroblast cell lines (MASEF, Mastomys natalensis embryo fibroblast and HEFL-12, human embryo fibroblast) in vitro. The maximum tolerated concentration for both cell lines was 25 micrograms/ml. The results indicate that the compound has potential to be used for treatment of several human and animal parasitic diseases.

Sympathomimetic effects of Scoparia dulcis L. and catecholamines isolated from plant extracts.

PubMed

Freire, S M; Torres, L M; Souccar, C; Lapa, A J

1996-06-01

The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro. Administration of the extract (0.5-2 mg kg-1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the alpha-adrenoceptor antagonist prazosin (1 mg kg-1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1-3 x 10(3) micrograms mL-1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10(-8)-10(-4)M). Prazosin (10(-7)M) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 micrograms mL-1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 microgram mL-1). In preparations of guinea-pig tracheal rings the aqueous fraction (1-3 x 10(3) micrograms mL-1) relaxed the muscle contraction induced by histamine (10(-4) M) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 microM). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract. The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is, however, unrelated to the previously reported analgesic and anti-inflammatory properties of the plant extract, but may explain its effectiveness upon topical application in the healing of mucosal and skin wounds.

[Bacteriological, pharmacokinetic and clinical evaluations of ceftriaxone in the pediatric field. Pediatric study group of ceftriaxone].

PubMed

Fujii, R; Meguro, H; Arimasu, O; Tagaya, M; Fujita, K; Sakata, H; Yoshioka, H; Maruyama, S; Sanae, N; Nagamatsu, I

1986-08-01

Ceftriaxone (CTRX), a new injectable cephem antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in the pediatric field by a study group organized with pediatricians from all over the country. The following are a summary of the results of the evaluation. Antibacterial effects: The inhibition of growth was attained for over 90% of strains of K. pneumoniae, H. influenzae and Salmonella spp. at the concentration of 0.10 micrograms/ml and of strains of S. pneumoniae and E. coli at the concentration of 2.0 micrograms/ml. The CTRX was proved to have excellent antibacterial effects. Absorption and excretion: Thirty minutes after one shot intravenous administration with 10, 20, 40 and 50 mg/kg of CTRX, its serum levels were 73, 124, 169 and 190 micrograms/ml, respectively, a clear tendency of dose-response relationship being noticed. The serum levels decreased only gradually and stayed as high as 10 to 20 micrograms/ml even after 12 hours. The half-lives of the drug were 5.5, 6.3, 6.0 and 4.7 hours for the 4 different dose levels, respectively. Following the intravenous injection with 10, 20 and 40 mg/kg, the urinary excretion rates were 55, 52 and 54%, respectively. Following the one shot intravenous administration or by the drip infusion for 30 minutes with about 50 mg/kg, CTRX levels in the cerebrospinal fluid ranged from 1 to 20.3 micrograms/ml in case of purulent meningitis (5 to 10 micrograms/ml in most cases). A total of 322 cases was enrolled. The efficacy of CTRX was evaluated in 295 cases out of the 322, excluding drop-outs and the cases which did not meet the protocols. The clinical efficacy rate was 94% of 191 cases where the causative bacteria were identified, CTRX being "excellent" in 108 cases and "effective" in 72. In the remaining 104 cases where the causative bacteria were not identified, the efficacy rate was 92%, CTRX being "excellent" in 42 cases and "effective" in 54. Furthermore, the efficacy rate was 89% of 18 cases infected with more than one kind of bacteria. The drug showed "excellent" or better effectiveness in 88% of 75 cases which had not responded to other antibiotics. Bacteriologically, 174 out of 216 strains (93%) which were judged to be causative bacteria disappeared with the use of CTRX. Eighty-five percent of 53 strains which had not responded to other antibiotics disappeared by the CTRX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

[Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat].

PubMed

Sumi, T

1993-03-01

Kindling model has been regarded as an experimental model for partial seizure with secondary generalized convulsion in human epilepsy. A number of pharmacological studies have been carried out to evaluate antiepileptic effects of conventional anticonvulsants on kindled seizures, mainly using amygdala kindled model. However, it is known that hippocampus is a more important site for human temporal epilepsy. It should therefore be considered appropriate to evaluate effects of antiepileptic drugs, not only on amygdaloid- but also on hippocampal-kindled seizures. In the present study, effects of chronically administered phenobarbital (PB) on amygdaloid- and hippocampal-kindled seizures were investigated. In the first session, cats were orally administered 6 mg/kg of PB for 15 days to obtain the serum level between 15 micrograms/ml and 25 micrograms/ml (optimal level for human epileptic seizure), then stimulation was carried out once a day for the following five days with suprathreshold stimulation intensity (100 microA higher than generalized seizure triggering threshold). For evaluation of drug efficacy, duration of afterdischarge and seizure severity were determined. After the end of session 1, session 2 started with 12 mg/kg of PB for 35-50 micrograms/ml serum level (subtoxic level) and continued in the same manner as stated above. PB was proved to be more effective for hippocampal- than for amygdaloid-kindled seizures. Generalized convulsions were easily suppressed in the level of 15-25 micrograms/ml and afterdischarge was totally suppressed in 33% of cats in the level of 35-50 micrograms/ml in the hippocampal-kindled group. However, amygdaloid-kindled seizures were more resistant to PB. It was difficult to suppress generalized convulsion in the level of 15-25 micrograms/ml, and total suppression of afterdischarge was extremely rare even in the higher serum level in amygdaloid-kindled cats. In addition, cats requiring a smaller number of stimuli to the completion of kindling tended to show more marked drug-resistance. Such tendency could be seen in both groups, although, more distinct in amygdaloid-kindled cats. Also evaluated were effects of PB on the secondary site kindled-seizures and it was shown that the potency of PB was less manifest in secondary site amygdaloid seizures than in primary site hippocampal seizures. These data show that the drug efficacy in the kindling model depends on the stimulated brain region as well as animals predisposition probably related to rapid acquisition of epileptogenesis. The intractability of temporal lobe epilepsy might be related to the site of epileptic focus and predisposition of patients as well.(ABSTRACT TRUNCATED AT 400 WORDS)

Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane.

PubMed Central

Danesi, R.; Del Bianchi, S.; Soldani, P.; Campagni, A.; La Rocca, R. V.; Myers, C. E.; Paparelli, A.; Del Tacca, M.

1993-01-01

The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [3H]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 micrograms ml-1. bFGF antisense oligomer (10 microM) reduced [3H]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 micrograms was a more potent inhibitor of angiogenesis than the combination of heparin 60 micrograms/hydrocortisone 50 micrograms; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (- 35 and - 29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone. Images Figure 1 Figure 4 PMID:7692920

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.

PubMed

Elisbão, Maria do Carmo M; Baldy, José Luís da S; Bonametti, Ana Maria; Reiche, Edna Maria V; Morimoto, Helena K; Pontello, Rubens; Matsuo, Tiemi; Ferelle, Antônio; Neves, Jayme

2003-12-01

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.

[Rapid identification of micro-constituents in monoammonium glycyrrhizinate raw materials by high-pressure solid phase extraction-high performance liquid chromatography-mass spectrometry].

PubMed

Yang, Xue-Dong; Tang, Xu-Yan; Sang, Lin

2012-11-01

To establish a method for rapid identification of micro-constituents in monoammonium glycyrrhizinate by high-pressure solid phase extraction-high performance liquid chromatography-mass spectrometry. HPLC preparative chromatograph was adopted for determining the optimal method for high-pressure solid phase extraction under optimal conditions. 5C18-MS-II column (20.0 mm x 20.0 mm) was used as the extraction column, with 35% acetonitrile-acetic acid solution (pH 2. 20) as eluent at the speed of 16 mL x min(-1). The sample size was 0.5 mL, and the extraction cycle was 4.5 min. Then, extract liquid was analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) after being concentrated by 100 times. Under the optimal condition of high-pressure solid phase extraction-high performance liquid chromatography-mass spectrometry, 10 components were rapidly identified from monoammonium glycyrrhizinate raw materials. Among them, the chemical structures of six micro-constituents were identified as 3-O-[beta-D-glucuronopyranosyl-beta-D-glucuronopyranosyl]-30-0-beta-D-apiopyranosylglycyrrhetic/3-O- [P-D-glucuronopyranosyl-beta-D-glucuronopyranosyl]-30-O-beta-D-arabinopyranosylglycyrrhetic, glycyrrhizic saponin F3, 22-hydroxyglycyrrhizin/18alpha-glycyrrhizic saponin G2, 3-O-[beta-D-rhamnopyranosyl]-24-hydroxyglycyrrhizin, glycyrrhizic saponin J2, and glycyrrhizic saponin B2 by MS(n) spectra analysis and reference to literatures. Four main chemical components were identified as glycyrrhizic saponin G2, 18beta-glycyrrhizic acid, uralglycyrrhizic saponin B and 18alpha-glycyrrhizic acid by liquid chromatography, MS(n) and ultraviolet spectra information and comparison with reference substances. The method can be used to identify chemical constituents in monoammonium glycyrrhizinate quickly and effectively, without any reference substance, which provides basis for quality control and safe application of monoammonium glycyrrhizinate-related products.

The effect of substance P on the antigen-induced bronchoconstriction in guinea pigs.

PubMed

Nagai, H; Tsuji, F; Koda, A

1990-03-01

The effect of substance P (SP) on the antigen-induced bronchoconstriction in vitro and in vivo was investigated in guinea pigs. SP caused the contraction of isolated non-sensitized guinea pig tracheal muscle at concentrations between 10(-9) to 10(-7) g/ml. The elimination of epithelium in the tracheal muscle produced a slight enhancement of SP response as compared to control. Antigen-induced contraction of isolated sensitized guinea pig tracheal muscle was slightly enhanced by the pretreatment with SP at a concentration of 10(-9) g/ml. The SP-induced enhancement of antigen-induced contraction was significantly augmented by the elimination of epithelium of sensitized tracheal muscle. Moreover, the clear bronchoconstriction was observed by the infusion of SP (1 micrograms/min) intravenously, but not by the infusion of SP at the rates between 0.1 and 0.01 micrograms/min. Antigen-induced asthmatic respiratory disorder was accelerated temporarily by the infusion of subthreshold SP (0.1 microgram/min). The reactivity of bronchial smooth muscle measured by repeated injection of acetylcholine was significantly potentiated by the infusion of subthreshold SP (0.1 microgram/min). These results suggest that SP has dual actions in the contractile response of guinea pig airway smooth muscle. One is the direct contractile activity, and the other one is enhancing activity of antigen- and acetylcholine-induced bronchoconstriction.

Determination of teicoplanin concentrations in serum by high-pressure liquid chromatography.

PubMed Central

Joos, B; Lüthy, R

1987-01-01

An isocratic reversed-phase high-pressure liquid chromatographic method for the determination of six components of the teicoplanin complex in biological fluid was developed. By using fluorescence detection after precolumn derivatization with fluorescamine, the assay is specific and highly sensitive, with reproducibility studies yielding coefficients of variation ranging from 1.5 to 8.5% (at 5 to 80 micrograms/ml). Response was linear from 2.5 to 80 micrograms/ml (r = 0.999); the recovery from spiked human serum was 76%. An external quality control was performed to compare this high-pressure liquid chromatographic method (H) with a standard microbiological assay (M); no significant deviation from slope = 1 and intercept = 0 was found by regression analysis (H = 1.03M - 0.45; n = 15). PMID:2957953

Comparison of effects of albendazole sulfoxide on in vitro produced bovine embryos and rat embryos.

PubMed

Piscopo, S E; Smoak, I W

1997-09-01

To evaluate and compare effects of albendazole sulfoxide (ABZSO) on rat embryos and bovine embryos produced in vitro. In vitro produced bovine embryos. Rat embryos recovered from naturally bred Sprague-Dawley rats. 4- and 8-cell bovine embryos were randomly allocated to ABZSO or vehicle control groups. After 48 hours, embryos were evaluated for cell number and blastomere morphology. Rat embryos of similar stages, flushed from the uterine tube on gestational day 2-5, were randomly allocated to treatment or control groups. After 24 hours, embryos were evaluated as described previously. 44% of control bovine embryos divided in culture (> or = 16-cell stage). Fifteen percent of the controls had morphologic abnormalities, including disparity in blastomere size and cytoplasmic vacuoles and stippling. Treated (> or = 1 microgram of ABZSO/ml) bovine embryos differed (P < 0.0001) from controls, with 4% development and 93% abnormal morphology. Forty-five percent of control rat embryos divided in culture. Treated (> or = 500 ng of ABZSO/ml) rat embryos differed (P < 0.0003) from controls with regard to ability to divide. There were no consistent morphologic abnormalities in rat embryos. In vitro produced bovine embryos were susceptible to ABZSO at a concentration > or = 1 microgram/ ml, resulting in decreased ability to divide and presence of gross morphologic abnormalities. Rat embryos produced in vivo and exposed in vitro to ABZSO at a concentration > or = 500 ng/ml had decreased ability to divide in culture. Despite severe effects of ABZSO (> or = 1 microgram/ml) on bovine embryo development in vitro, it is beyond the scope of this study to speculate whether a therapeutic dosage of albendazole (10 mg/kg of body weight) would result in necessary concentrations of ABZSO in vivo to disrupt embryogenesis.

In vitro activity of roxithromycin against the Mycobacterium tuberculosis complex.

PubMed Central

Rastogi, N; Goh, K S; Ruiz, P; Casal, M

1995-01-01

Roxithromycin has recently been shown to possess significant in vitro activity against a variety of atypical mycobacteria such as the M. avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens like M. chelonei and M. fortuitum. In the present investigation, screening of its in vitro activity was further extended by testing it against 34 strains belonging to the M. tuberculosis complex (including M. tuberculosis, M. africanum, M. bovis, and M. bovis BCG). The MICs were determined by the radiometric BACTEC 460-TB methodology at pHs of both 6.8 and 7.4, as well as with 7H10 agar medium by the 1% proportion method. With the exception of M. bovis BCG (MIC ranges, 0.5 to 4 micrograms/ml at pH 6.8 and 0.25 to 2 micrograms/ml at pH 7.4), MICs for all of the isolates were significantly greater (MIC ranges, 32 to > 64 micrograms/ml at pH 6.8 and 16 to > 32 micrograms/ml at pH 7.4) than those reported previously for atypical mycobacteria. Roxithromycin MICs of 64 or > 64 micrograms/ml for all of the M. tuberculosis isolates screened were found by the 7H10 agar medium method. Roxithromycin, however, showed a pH-dependent bactericidal effect against M. tuberculosis because the drug was relatively more active when it was used at pH 7.4 than when it was used at pH 6.8. We conclude that roxithromycin per se is not a drug of choice for the treatment of M. tuberculosis infection or disease; however, considering its pharmacokinetics, eventual anti-tubercle bacillus activity in an in vivo system cannot yet be excluded. We suggest that the use of roxithromycin in chemoprophylactic regimens for the prevention of opportunistic infections (including M. avium complex infections) in patients with AIDS should be carefully monitored, and patients should be enrolled in such a regimen only after it has been excluded that the patient das an underlying infection of disease caused by M. tuberculosis. PMID:7625806

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose.

PubMed

Bryan, J P; Sjogren, M H; Macarthy, P; Cox, E; Legters, L J; Perine, P L

1992-01-01

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chronobiological studies on effect of cyclosporin A (CsA) against adult male worms of Schistosoma mansoni in vitro].

PubMed

Liu, J; Chappell, L H

1998-01-01

To study the action mode of cyclosporin A (CsA) against Schistosoma mansoni in vitro. MF1 mice were infected with Schistosoma mansoni cercariae for 6 weeks when the adult worms were recovered by portal perfusion. The male worms of S. mansoni recovered were exposed to varying concentrations of CsA at 8, 16, and 24 h in vitro. Drug induced damage to the male worm surface was chrono-biologically observed throughout these experiments by SEM. After the male worms of S. mansoni were incubated with 1 microgram/ml CsA for 8-24 h, the tegument showed swelling of ridges with appearance of holes on their surface and detachment of a part of spines. The above damage of the tegument became more evident in male worms after incubation with 10, 15, 20 micrograms/ml CsA for 8-24 h. Moreover, incubation of male worms with 25 micrograms/ml CsA for 8-24 h resulted in significant deformation and disruption of tegument, rupture of ridges and detachment of spines. The tegumental damage of male worms of S. mansoni was dose- and time-dependent. The antischistosomal action of CsA is direct, the schistosome tegument appears to be the main site for CsA attack.

Performance characteristics of two bioassays and high-performance liquid chromatography for determination of flucytosine in serum.

PubMed Central

St-Germain, G; Lapierre, S; Tessier, D

1989-01-01

We compared the accuracy and precision of two microbiological methods and one high-pressure liquid chromatography (HPLC) procedure used to measure the concentrations of flucytosine in serum. On the basis of an analysis of six standards, all methods were judged reliable within acceptable limits for clinical use. With the biological methods, a slight loss of linearity was observed in the 75- to 100-micrograms/ml range. Compared with the bioassays, the HPLC method did not present linearity problems and was more precise and accurate in the critical zone of 100 micrograms/ml. On average, results obtained with patient sera containing 50 to 100 micrograms of flucytosine per ml were 10.6% higher with the HPLC method than with the bioassays. Standards for the biological assays may be prepared in serum or water. PMID:2802566

Antiplasmodial activity of four Kenyan medicinal plants.

PubMed

Omulokoli, E; Khan, B; Chhabra, S C

1997-04-01

A preliminary antiplasmodial and phytochemical screening of four Kenyan medicinal plants was carried out. The medicinal plants were extracted and tested for in vitro antiplasmodial activity against chloroquine-sensitive (K67) and chloroquine-resistant (ENT36) strains of Plasmodium falciparum. Out of 16 extracts, 12 were active against ENT36 strain while seven were active against K67 strain, that is, IC50 < or = 50 micrograms/ml. The most active extracts on both strains were those of leaves of Phyllanthus reticulatus Poir, and Suregada zanzibariensis Baill. (Euphorbiaceae) with IC50 < or = 10 micrograms/ml. The stembark of Terminalia spinosa Engl. (Combretaceae) and the stems of Dissotis brazzae Cogn. (Melastomataceae) had IC50 < or = 10 micrograms/ml for strains K67 and ENT36, respectively. A preliminary phytochemical analysis of these plants revealed the presence of different classes of primary and secondary metabolites.

[Interfering effects of radix Salviae miltiorrhizae and lingustrazine on mm-LDL activating BKCa in ECV304 cell].

PubMed

Lin, L; Zheng, Y F; Qu, J H; Bao, G H

2001-08-01

To observe the action of minimally modified low density lipoprotein (mm-LDL) on BKCa in ECV304 cell and the interfering effects of radix salviae miltiorrhizae extract powder 764-3 (30 micrograms/ml) and lingustrazine (200 micrograms/ml) on this action. The cell-attached configuration of patch clamp technique was applied. mm-LDL (100 micrograms/ml) potentiated the activity of BKCa in ECV304. While 764-3 and lingustrazine abolished it. mm-LDL acted on vascular endothelial cell ECV304 could rapidly activate the activity of BKCa and might result in the increase of electro-chemical gradient for the resting Ca2+ influx, thus resting cytoplasmic concentration of calcium could be elevated and endothelial dysfunction would be induced. 764-3 and lingustrazine might have the protective action through decreasing the activity of BKCa.

Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng.

PubMed

Xiong, Jing; Guo, Jianxin; Huang, Luosheng; Meng, Boyu; Ping, Qineng

2008-08-06

The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC0-6h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0-infinity of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52+/-53.95 and 1961.72+/-686.60 microg ml(-1) h, compared with 7.87+/-2.85 and 148.58+/-36.73 microg ml(-1) h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.

Depletion of proton motive force by nisin in Listeria monocytogenes cells.

PubMed

Bruno, M E; Kaiser, A; Montville, T J

1992-07-01

The basal proton motive force (PMF) levels and the influence of the bacteriocin nisin on the PMF were determined in Listeria monocytogenes Scott A. In the absence of nisin, the interconversion of the pH gradient (Z delta pH) and the membrane potential (delta psi) led to the maintenance of a fairly constant PMF at -160 mV over the external pH range 5.5 to 7.0. The addition of nisin at concentrations of greater than or equal to 5 micrograms/ml completely dissipated PMF in cells at external pH values of 5.5 and 7.0. With 1 microgram of nisin per ml, delta pH was completely dissipated but delta psi decreased only slightly. The action of nisin on PMF in L. monocytogenes Scott A was both time and concentration dependent. Valinomycin depleted only delta pH, whereas nigericin and carbonyl cyanide m-chlorophenylhydrazone depleted only delta psi, under conditions in which nisin depleted both. Four other L. monocytogenes strains had basal PMF parameters similar to those of strain Scott A. Nisin (2.5 micrograms/ml) also completely dissipated PMF in these strains.

Effects of ceftazidime, a betalactam antibiotic, on murine haemopoiesis in vitro.

PubMed

Hauser, S P; Udupa, K B; Lipschitz, D A

1994-04-01

Agranulocytosis has been reported in 5-15% of patients treated with high-dose betalactam antibiotics (BLA). We investigated the toxic effect of ceftazidime (CEF) as a representative of these antibiotics on colony-forming unit-granulocyte/macrophage (CFU-GM), on burst-forming unit-erythroid (BFU-E) colony growth and on myelopoiesis in murine long-term bone marrow culture (mLTBMC). The CEF concentration resulting in a 50% inhibition of growth was 146 micrograms/ml (267 microM) for CFU-GM, 132 micrograms/ml (241 microM) for BFU-E and 180 micrograms/ml (329 microM) for myeloid cell production in the supernatant of mLTBMC. Following addition of CEF to mLTBMC, CFU-GM remained low for 1 week and total myeloid cell production remained low for 2 weeks after removal of CEF from culture. Thereafter the values returned to control levels. The myeloid differential counts in the supernatant and adherent layers demonstrated a 'maturation arrest', which could be overcome by simultaneously adding all-trans retinoic acid to culture. These results demonstrate that CEF has reversible inhibitory effects on myelopoiesis and highlight the utility of in vitro haemopoietic assays as models to examine drug-induced haemopoietic dyscrasias.

Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM-1470).

PubMed Central

Kusaka, M.; Sudo, K.; Matsutani, E.; Kozai, Y.; Marui, S.; Fujita, T.; Ingber, D.; Folkman, J.

1994-01-01

Recently, we reported the anti-angiogenic action along with anti-tumour activity of TNP-470 (AGM-1470). In this study, the effect of TNP-470 on the growth of human umbilical vein endothelial (HUVE) cells was examined. TNP-470 inhibited the growth of HUVE cells in a biphasic manner. The inhibition was cytostatic in the first phase (complete inhibition at 300 pg ml-1 to 3 micrograms ml-1 with an IC50 of 15 pg ml-1) and cytotoxic in the second phase (> or = 30 micrograms ml-1). The cytostatic inhibition of HUVE cell growth by TNP-470 was durable after washing out TNP-470 in culture. Incorporation of thymidine but not uridine and leucine by HUVE cells was inhibited in the first phase, while that of all three compounds was inhibited in the second phase. Human and rat endothelial cells among various types of cells were the most sensitive to the cytostatic inhibition, while differences in the cytotoxic inhibition were minimal. These results suggest that TNP-470 exerts its specific anti-angiogenic action by inhibiting cytostatically growth of endothelial cells in a relatively specific manner. PMID:8297716

Penetration of ciprofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans.

PubMed Central

Mertes, P M; Voiriot, P; Dopff, C; Scholl, H; Clavey, M; Villemot, J P; Canton, P; Dureux, J B

1990-01-01

The penetration of ciprofloxacin into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study involving 36 patients undergoing mitral and/or aortic valve replacement. Patients were divided into two groups of 18. Group 1 patients were administered a single 400-mg intravenous dose of ciprofloxacin over a 1-h period. Group 2 patients received a 750-mg dose of ciprofloxacin orally every 12 h over the 48-h period preceding surgery. In this group, the last dose of ciprofloxacin consisted of an intravenous infusion of 400 mg. Concentrations of ciprofloxacin in plasma and tissue were assayed by high-performance liquid chromatography. Peak and trough levels in plasma were, respectively, 6.19 +/- 1.73 and 0.54 +/- 0.25 micrograms/ml in group 1 patients and 11.59 +/- 3.95 and 0.89 +/- 0.57 micrograms/ml in group 2 patients. Levels of ciprofloxacin in plasma remained significantly higher in group 2 than in group 1 until 12 h postinfusion (P less than 0.05). Concentrations of ciprofloxacin in heart valves and myocardia rose rapidly by 1 h postinfusion and remained greater than the MICs for usually susceptible pathogens for at least 5 h. Peak concentrations in myocardia were achieved by hour 1 and were 31.6 +/- 25.0 micrograms/g for group 1 and 21.8 +/- 13.0 micrograms/g for group 2. Peak concentrations in heart valves, achieved between hours 1 and 3, were 5.8 +/- 3.2 and 8.3 +/- 3.1 micrograms/g for groups 1 and 2, respectively. In both groups, peak concentrations in mediastinal fat were lower and achieved later. These were 3.1 +/- 3.8 micrograms/g in group 1 and 2.0 +/- 1.8 micrograms/gram in group 2 and were achieved between hours 3 and 5 and hours 1 and 3, respectively. In conclusion, the good diffusion of ciprofloxacin into heart tissue warrants its use for the treatment of bacterial endocarditis. On the other hand, low and delayed concentrations in mediastinal fat could limit its value as an antibiotic prophylactic agent in a cardiovascular surgical setting when administered immediately (less than 3 h) before surgery. PMID:2185690

Effect of inoculant strain and organic matter content on kinetics of 2,4-dichlorophenoxyacetic acid degradation in soil.

PubMed Central

Greer, L E; Shelton, D R

1992-01-01

We monitored rates of degradation of soluble and sorbed 2,4-dichlorophenoxyacetic acid (2,4-D) in low-organic-matter soil at field capacity amended with 1, 10, or 100 micrograms of 2,4-D per g of wet soil and inoculated with one of two bacterial strains (MI and 155) with similar maximum growth rates (mu max) but significantly different half-saturation growth constants (Ks). Concentrations of soluble 2,4-D were determined by analyzing samples of pore water pressed from soil, and concentrations of sorbed 2,4-D were determined by solvent extraction. Between 65 and 75% of the total 2,4-D was present in the soluble phase at equilibrium, resulting in soil solution concentrations of ca. 8, 60, and 600 micrograms of 2,4-D per ml, respectively. Soluble 2,4-D was metabolized preferentially; this was followed by degradation of both sorbed (after desorption) and soluble 2,4-D. Rates of degradation were comparable for the two strains at soil concentrations of 10 and 100 micrograms of 2,4-D per g; however, at 1 microgram/g of soil, 2,4-D was metabolized more rapidly by the strain with the lower Ks value (strain MI). We also monitored rates of biodegradation of soluble and sorbed 2,4-D in high-organic-matter soil at field capacity amended with 100 micrograms of 2,4-D per g of wet soil and inoculated with the low-Ks strain (strain MI). Ten percent of total 2,4-D was present in the soluble phase, resulting in a soil solution concentration of ca. 30 micrograms of 2,4-D per ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1622212

Effect of inoculant strain and organic matter content on kinetics of 2,4-dichlorophenoxyacetic acid degradation in soil.

PubMed

Greer, L E; Shelton, D R

1992-05-01

We monitored rates of degradation of soluble and sorbed 2,4-dichlorophenoxyacetic acid (2,4-D) in low-organic-matter soil at field capacity amended with 1, 10, or 100 micrograms of 2,4-D per g of wet soil and inoculated with one of two bacterial strains (MI and 155) with similar maximum growth rates (mu max) but significantly different half-saturation growth constants (Ks). Concentrations of soluble 2,4-D were determined by analyzing samples of pore water pressed from soil, and concentrations of sorbed 2,4-D were determined by solvent extraction. Between 65 and 75% of the total 2,4-D was present in the soluble phase at equilibrium, resulting in soil solution concentrations of ca. 8, 60, and 600 micrograms of 2,4-D per ml, respectively. Soluble 2,4-D was metabolized preferentially; this was followed by degradation of both sorbed (after desorption) and soluble 2,4-D. Rates of degradation were comparable for the two strains at soil concentrations of 10 and 100 micrograms of 2,4-D per g; however, at 1 microgram/g of soil, 2,4-D was metabolized more rapidly by the strain with the lower Ks value (strain MI). We also monitored rates of biodegradation of soluble and sorbed 2,4-D in high-organic-matter soil at field capacity amended with 100 micrograms of 2,4-D per g of wet soil and inoculated with the low-Ks strain (strain MI). Ten percent of total 2,4-D was present in the soluble phase, resulting in a soil solution concentration of ca. 30 micrograms of 2,4-D per ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma concentrations of enrofloxacin in African grey parrots treated with medicated water.

PubMed

Flammer, K; Aucoin, D P; Whitt, D A; Prus, S A

1990-01-01

Plasma concentrations of enrofloxacin were measured four times during a 7-day treatment period in African grey parrots that were fed with enrofloxacin-medicated drinking water. Water medicated at doubling doses of 0.09, 0.19, 0.38, 0.75, 1.5, and 3.0 mg/ml achieved mean concentrations (+/- SEM) of 0.10 (+/- 0.05), 0.12 (+/- 0.05), 0.12 (+/- 0.03), 0.15 (+/- 0.05), 0.30 (+/- 0.11), and 0.20 (+/- 0.06) micrograms/ml, respectively. A portion of the administered enrofloxacin was metabolized to an equipotent metabolite, ciprofloxacin. Mean ciprofloxacin concentrations paralleled enrofloxacin concentrations but were lower, ranging from 0.04 to 0.27 micrograms/ml. Acceptance of medicated water was adequate at lower doses; however, at doses of 1.5 and 3.0 mg/ml, acceptance was unsatisfactory, and mean weight loss in these groups was significantly higher than the control group. Based on the concentrations achieved in these preliminary trials and the susceptibility patterns of gram-negative bacteria isolated from psittacine birds, drinking water medicated with enrofloxacin at 0.19-0.75 mg/ml might be effective for treating highly susceptible gram-negative bacterial infections in African grey parrots.

PAROTID FLUID CORTISOL AND CORTISONE.

DTIC Science & Technology

Concentrations of parotid fluid cortisol and cortisone, and of plasma dialyzable cortisol, were measured in normal men before and 2 hours after...of 8.5 to 17.7 micrograms/100 ml. after ACTH treatment, and to 39.4 micrograms/100 ml. after administration of the estrogen. However, parotid fluid...the increase in total plasma cortisol (which was over twice as high after administration of estrogen as of ACTH). Thus parotid fluid corticosteroids

Calorimetric determination of inhibition of ice crystal growth by antifreeze protein in hydroxyethyl starch solutions.

PubMed Central

Hansen, T N; Carpenter, J F

1993-01-01

Differential scanning calorimetry and cryomicroscopy were used to investigate the effects of type I antifreeze protein (AFP) from winter flounder on 58% solutions of hydroxyethyl starch. The glass, devitrification, and melt transitions noted during rewarming were unaffected by 100 micrograms/ml AFP. Isothermal annealing experiments were undertaken to detect the effects of AFP-induced inhibition of ice crystal growth using calorimetry. A premelt endothermic peak was detected during warming after the annealing procedure. Increasing the duration or the temperature of the annealing for the temperature range from -28 and -18 degrees C resulted in a gradual increase in the enthalpy of the premelt endotherm. This transition was unaffected by 100 micrograms/ml AFP. Annealing between -18 and -10 degrees C resulted in a gradual decrease in the premelt peak enthalpy. This process was inhibited by 100 micrograms/ml AFP. Cryomicroscopic examination of the samples revealed that AFP inhibited ice recrystallization during isothermal annealing at -10 degrees C. Annealing at lower temperatures resulted in minimal ice recrystallization and no visible effect of AFP. Thus, the 100 micrograms/ml AFP to have a detectable influence on thermal events in the calorimeter, conditions must be used that result in significant ice growth without AFP and visible inhibition of this process by AFP. Images FIGURE 8 PMID:7690257

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reid, A.A.; Fleming, P.J.; Lake, C.R.

We modified a norepinephrine radioenzymatic method for determination of plasma phenylpropanolamine (PPA) concentrations. PPA is converted to N(methyl-/sup 3/H)ephedrine ((/sup 3/H)EPD) by the enzyme phenylethanolamine N-methyltransferase (PNMT) and S-(methyl-/sup 3/H)adenosyl-L-methionine ((/sup 3/H)AdoMet). The product, (/sup 3/H)EPD, is isolated from unreacted (/sup 3/H)AdoMet and labeled side products by an organic extraction and a TLC procedure. In addition, a preincubation organic extraction procedure is included to remove inhibitors of PNMT from plasma and to concentrate the sample for enhanced enzymatic conversion. In order to accurately quantitate PPA across the wide range of possible concentrations, the assay is conducted at two plasma volumes.more » PPA concentrations between 0.3 and 50 micrograms/liter can be detected with 1 ml of plasma, while concentrations between 4 and 1500 micrograms/liter can be detected with 0.1 ml of plasma. The intra-assay coefficients of variation (CVs) are 9.3 and 5.7% at 0.5 and 1500 micrograms/liter, respectively, while the mean interassay CV is 13.8%.« less

N-nitrosodimethylamine, nitrate and nitrate-reducing microorganisms in human milk.

PubMed

Uibu, J; Tauts, O; Levin, A; Shimanovskaya, N; Matto, R

1996-10-01

Of 54 milk samples from 54 healthy nursing women analysed for volatile N-nitrosamines, 42 appeared negative. Trace amounts (below the detection limit 0.5 microgram l-1) of N-nitrosodimethylamine were detected in the milk of 10 mothers and two samples contained this compound at 1.1 and 1.2 micrograms 1-1 respectively. Almost all samples investigated contained nitrate (mean 2.9 +/- 2.3 mg1-1 and nitrate reducing microorganisms (mean 4.2 +/- 1.0 log ml-1). The recent finding of N-nitrosodimethylamine in human milk gives evidence of the continuous endogenous formation of N-nitrosamines.

21 CFR 524.814 - Eprinomectin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... mg (1 mL) per 10 kilograms (kg) of body weight (500 micrograms/kg) applied topically along backbone...); cattle grubs (all parasitic stages Hypoderma lineatum, H. bovis); lice (Damalinia bovis, Linognathus...

21 CFR 524.814 - Eprinomectin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... mg (1 mL) per 10 kilograms (kg) of body weight (500 micrograms/kg) applied topically along backbone...); cattle grubs (all parasitic stages Hypoderma lineatum, H. bovis); lice (Damalinia bovis, Linognathus...

21 CFR 524.814 - Eprinomectin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... mg (1 mL) per 10 kilograms (kg) of body weight (500 micrograms/kg) applied topically along backbone...); cattle grubs (all parasitic stages Hypoderma lineatum, H. bovis); lice (Damalinia bovis, Linognathus...

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

PubMed

Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

1990-01-01

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Impact of C-reactive protein (CRP) on surfactant function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J.J.; Sanders, R.L.; McAdam, K.P.

1989-12-01

Plasma levels of the acute-phase reactant, C-reactive protein (CRP), increase up to one thousand-fold as a result of trauma or inflammation. CRP binds to phosphorylcholine (PC) in a calcium-ion dependent manner. The structural homology between PC and the major phospholipid component of surfactant, dipalmitoyl phosphatidylcholine (DPPC), led to the present study in which we examined if CRP levels might be increased in patients with adult respiratory distress syndrome (ARDS), and subsequently interfere with surfactant function. Our results showed that CRP levels in the bronchoalveolar fluid (BALF) was increased in patients with ARDS (97.8 +/- 84.2 micrograms/mg total protein vs. 4.04more » +/- 2.2 micrograms/mg total protein in normals). Our results show that CRP binds to liposomes containing DPPC and phosphatidylglycerol (PG). As a result of this interaction, CRP inhibits the surface activity of a PG-DPPC mixture when tested with a Wilhelmy surfactometer or with the Enhorning pulsating bubble apparatus. Furthermore, the surface activity of a clinically used surfactant replacement, Surfactant TA (2 mg/ml), was also severely impaired by CRP in a dose-dependent manner (doses used ranging from 24.5 to 1,175 micrograms/ml). In contrast, human serum albumin (HSA) at 500 and 900 micrograms/ml had no inhibitory effect on Surfactant TA surface activity. These results suggest that CRP, although not an initiating insult in ARDS, may contribute to the subsequent abnormalities of surfactant function and thus the pathogenesis of the pulmonary dysfunction seen in ARDS.« less

A modified spectrophotometric assay to estimate deglycosylation of steroidal saponin to sapogenin by mixed ruminal microbes.

PubMed

Wang, Yuxi; McAllister, Tim A

2010-08-30

The lack of a method for measuring deglycosylation of saponins in ruminal fluid has limited the ability to investigate the impact of these compounds on rumen microorganisms. A simple spectrophotometric assay was adapted and a protocol developed to enable measurement of steroidal saponin and sapogenin in ruminal fluid. The procedure was used for in vitro determination of deglycosylation activity of rumen bacteria obtained from cattle fed or not fed Yucca schidigera saponin, and to determine the relative deglycosylase activities of extracellular and cell-associated enzymes from ruminal content. Modifications to the spectrophotometric assay (i.e. heating time shortened to 10 min and 0.5 mL dH(2)O added to the reaction mixture) improved the stability of the optical density (425 nm) of the chromophore for up to 24 h post-reaction. Centrifugation (12 000 x g, 20 min) enabled differential estimations of steroidal saponin and sapogenin in ruminal fluid. Steroidal saponin added to defaunated ruminal fluid (dRF) or clarified ruminal fluid (cRF) was recovered completely from the mixture as saponin + sapogenin (99.1% and 100.6%, respectively), whereas saponin recovery from the supernatant of dRF was greatly reduced (P < 0.001) compared to that from supernatant of cRF (58.5 vs. 98.7%). Saponin recoveries from the supernatants of dRF and cRF did not differ between donor cattle fed or not fed Yucca schidigera saponin (59.2 vs. 57.3% and 98.4 vs. 99.3%, respectively). The majority (89-90%) of saponin added to a ruminal extracellular enzyme preparation was recoverable in supernatant after 24 h, compared with only 26-32% remaining in supernatant from incubation with a cell-associated enzymes fraction. Mixed rumen bacteria deglycosylate steroidal saponin to sapogenin, at activity levels unaffected by prior exposure to saponin, but they were unable to degrade the sapogenin core structure. Deglycosylation activity occurred primarily in the cell-associated enzyme fraction of ruminal content. Copyright (c) 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.

Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases.

PubMed Central

Jacoby, G A; Carreras, I

1990-01-01

Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases. PMID:2193623

In vitro susceptibility of rabbit strains of Clostridium spiroforme to antimicrobial agents.

PubMed

Carman, R J; Wilkins, T D

1991-08-30

Using an agar dilution method we measured the minimum inhibitory concentration (MIC) of 12 antimicrobial agents against 11 strains of iota-toxigenic strains of Clostridium spiroforme. Each strain was isolated from a separate outbreak of toxic diarrhoea of rabbits. Vancomycin and bacitracin, both agents used to treat intestinal clostridioses of humans and other animals, had a relatively high MIC (8 micrograms/ml or more). Metronidazole was uniformly active against C. spiroforme. With MIC of 8 micrograms/ml or more, both lincomycin (11 strains) and erythromycin (9 strains) were relatively inactive against C. spiroforme, conversely, penicillin G was active (MIC for 8 strains was 0.5 micrograms/ml or less). Exposure to any one of these drugs has been implicated as a predisposing factor for C. spiroforme mediated diarrhoea of rabbits. The greatest variation in MIC was seen for erythromycin (8-fold), penicillin G (8-fold) and tetracycline (16-fold).

Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.

PubMed

Hohmann, Nicolas; Kocheise, Franziska; Carls, Alexandra; Burhenne, Jürgen; Haefeli, Walter E; Mikus, Gerd

2015-02-01

We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics. Dose-normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1, 42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1) [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]). The pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity. © 2014 The British Pharmacological Society.

Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs

NASA Technical Reports Server (NTRS)

O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

1993-01-01

The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.

An LC-MS/MS method for simultaneous determination of three Polygala saponin hydrolysates in rat plasma and its application to a pharmacokinetic study.

PubMed

Wang, Qian; Xiao, Bing-Xin; Pan, Rui-Le; Liu, Xin-Min; Liao, Yong-Hong; Feng, Li; Cao, Fang-Rui; Chang, Qi

2015-07-01

Radix Polygala has a long history of use as a sedative in traditional Chinese medicine and its major ingredients are saponins, which are recognized effective in memory improvement but highly toxic to gastricintestinal mucosa. Polygala saponin hydrolysates (PSH), an alkaline hydrolysis product and also the intestinal metabolites of the saponins, exhibited stronger effects in improving memory of mice and had less toxicity than its original saponins. The present study aims to develop a sensitive LC-MS/MS method for simultaneously determining PSH three major active components, 3,4,5-trimethoxycinnamylic acid (TMCA), p-methoxycinnamylic acid (PMCA) and tenuifolin (TF), in rat plasma and apply the method to a pharmacokinetic study. The acidic plasma (100μl) was treated by liquid-liquid extraction with ethyl acetate and reconstituted sample was analyzed on a C18 column eluted with acetonitrile-water (50:50) containing 0.2% formic acid at 0.4ml/min. The mass detection in negative electrospray ionization was used. The ion pairs for multiple reaction monitoring were set at m/z 237.0/103.0, 177.0/116.6 and 679.5/425.3 for TMCA, PMCA and TF, respectively. Their pharmacokinetic profiles were studied in rats after intravenous and oral dose of PSH at 20 and 100mg/kg, respectively. The calibration curves had good linearity (r(2)>0.99) for TMCA, PMCA and TF within the tested concentration ranges. The limits of detection and quantification were 1, 10, 0.5ng/ml and 10.0, 20.0, 1.0ng/ml, respectively. The intra-day and inter-day precisions were less than 18.9% and accuracies between 93.2% and 113.3%, and the extraction recovery ranged from 91.2% to 112.1% for all analytes. The pharmacokinetic study showed that TMCA, PMCA and TF could be rapidly absorbed into the circulation and reached their peak concentrations at about 9.1, 9.0 and 24.0min, respectively. TF had a lower oral bioavailability (2.0%) than TMCA (90.1%) and PMCA (96.5%), but it remained in the body much longer (t1/2, λz, 4.8h, oral dose) than TMCA (0.6h) and PMCA (0.9h). A sensitive LC-MS/MS method was developed and applied to a pharmacokinetic study of TMCA, PMCA and TF of PSH in rats. The three components are proved to be bio-available active components of PSH and might display their in vivo pharmacological activities at different levels and different time periods after oral administration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Circannual and circadian rhythms in the concentration of corticosterone in the plasma of the edible frog (Rana esculenta L.).

PubMed

Dupont, W; Bourgeois, P; Reinberg, A; Vaillant, R

1979-01-01

For a period of 21 months between May 1974 and September 1976, circadian variations in the plasma concentration of corticosterone were studied by competitive protein-binding techniques in mature male and female edible frogs living in their natural environment. Blood samples were taken from 8 to 12 frogs six times daily and conventional and cosinor methods were used for statistical analysis. Circadian rhythms were not detected during February and March (time of hibernation). Circannual rhythms were detected in three parameters of the circadian rhythm. The mean concentration of corticosterone over a 24 h period (24 h mean) reached a peak on 1 May (between 15 April and 15 May; 95% limits of confidence); the annual mean value of the 24 h means was 1.97 +/- 0.25 (S.E.M.) microgram/100 ml, with an amplitude of 0.66 microgram/100 ml (0.53--0.79 microgram/100 ml; 95% limits of confidence). Circadian variations in the concentration of corticosterone were largest in May (peak of reproductive activity). The times at which the peak concentration of corticosterone occurred showed circannual variations: peak values were detected around 24.00 h in May, 19.00 h in July and 08.00 h in November. Both circadian and circannual variations have therefore been demonstrated in an endocrine function of an amphibian in its natural habitat.

Induction of human antigen-specific suppressor factors in vitro.

PubMed Central

Kontiainen, S; Woody, J N; Rees, A; Feldmann, M

1981-01-01

Based on methods used for the in vitro induction of antigen-specific suppressor cells in the mouse, we have cultured Ficoll-Isopaque-separated human blood cells with high dose of antigen (100 microgram/ml) in Marbrook culture vessels for 4 days. The resulting cells, when further recultured for 24 hr with a low dose of antigen (1 microgram/ml), released into the supernatant material, termed 'suppressor factor', which inhibited, in an antigen-specific manner, the antibody response of mouse spleen cells in culture. The suppressor factor was analysed using immunoabsorbents, and was bound to and eluted from specific antigen, concanavalin A and lentil lectin, anti-human Ia antibodies, and anti-mouse suppressor factor antibodies, but was not bound to antibodies against human IgG. PMID:6169475

[Pharmacokinetics and clinical studies of flomoxef in the pediatric field].

PubMed

Motohiro, T; Oda, K; Aramaki, M; Kawakami, A; Tanaka, K; Koga, T; Shimada, Y; Tomita, S; Sakata, Y; Fujimoto, T

1987-08-01

Flomoxef (FMOX, 6315-S), a new intravenous cephem antibiotics, was administered to a total of 11 cases with their ages ranging from 7 years and 4 months to 10 years and 10 months. Among them, two were administered with (FMOX at) a dose level of 10 mg/kg, three each with 20 mg/kg and 40 mg/kg using one shot intravenous injection, and the remaining 3 with 40 mg/kg by intravenous drip infusion over 30 minutes. Plasma concentrations, urine concentrations and urinary recovery rates were determined. The clinical efficacy of FMOX was evaluated in 2 cases with tonsillitis, 45 with acute pneumonia, 10 with urinary tract infections, 2 with purulent lymphadenitis, and 2 with abscess, a total of 61 cases. Of these cases, one case of pneumonia in which a side effect occurred was excluded from the evaluation because the treatment was interrupted short of the required period. In the remaining 60 cases, the mean daily dose was 79.3 mg/kg in 3 or 4 divided doses and, except one case treated by 30-minute intravenous drip infusion, all cases were treated by one shot intravenous injection for a mean period of 6 days. Bacteriological effects of FMOX, its side effects and influences on laboratory test values were also investigated. 1. Maximum plasma concentrations after one shot intravenous injections of FMOX occurred at 5 minutes after administration regardless of dose levels (10 mg/kg in 2 cases, 20 mg/kg in 3 and 40 mg/kg in 3). Mean peak values obtained upon the 3 different dose levels were 62.5, 103.1 and 244.7 micrograms/ml, respectively. Mean plasma half-lives were 0.670, 0.915 and 0.595 hour, and mean AUCs were 33.0, 65.2 and 133.1 micrograms.hr/ml, respectively. Thus, a positive dose-response relationship was found among the 3 doses. 2. Plasma concentrations after 30-minute intravenous drip infusions of FMOX at 40 mg/kg always reached a peak at 30 minutes after the initiation of infusion, i.e. at the completion of infusion, and the mean value for 3 administrations was 151.0 micrograms/ml. The mean half-life was 0.973 hour and the mean AUC was 149.1 micrograms.hr/ml. 3. Maximum concentrations in urine after one shot intravenous injections of FMOX were always obtained in 0 approximately 2 hours after administration regardless of dose levels (10 mg/kg, 2 cases, 20 mg/kg, 3 cases and at 40 mg/kg, 3 cases) and mean values for the 3 dose levels were 2,570, 4,410 and 6,290 micrograms/ml, respectively. Thus, urine concentrations were also dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacological attempts to improve the bioavailability of oral etoposide.

PubMed

Joel, S P; Clark, P I; Heap, L; Webster, L; Robbins, S; Craft, H; Slevin, M L

1995-01-01

Etoposide demonstrates incomplete and variable bioavailability after oral dosing, which may be due to its concentration and pH-dependent stability in artificial gastric and intestinal fluids. The use of agents that may influence etoposide stability and, thereby, bioavailability, was investigated in a number of clinical studies. Drugs that influence the rate of gastric emptying, while modulating the time of drug absorption, did not significantly alter the etoposide area under the concentration-time curve (AUC) or bioavailability. Specifically, metoclopramide had little effect on the etoposide absorption profile and did not significantly alter the AUC (AUC with etoposide alone, 68.4 +/- 20.3 micrograms ml-1 h, versus 74.3 +/- 25.9 micrograms ml-1 h with metoclopramide), suggesting that in most patients the drug is already emptied rapidly from the stomach. In contrast, propantheline produced a dramatic effect on etoposide absorption, delaying the time of maximal concentration tmax from 1.1 to 3.5 h (P < 0.01), but again without a significant improvement in drug AUC or bioavailability across the 24-h study period (AUC with etoposide alone 78.3 +/- 19.1 micrograms ml-1 h, versus 88.1 +/- 23.6 micrograms ml-1 h with propantheline). The effect of these drugs on the absorption of oral paracetamol, a drug included in the study as a marker of gastric emptying, was exactly the same as that found for etoposide, with no change in AUC being observed after metoclopramide or propantheline administration but a significant delay in tmax being seen on co-administration with etoposide and propantheline. The co-administration of ethanol or bile salts (agents that significantly improved the stability of etoposide in artificial intestinal fluid) with oral etoposide similarly had no effect on improving the etoposide AUC or reducing the variability in AUC, suggesting that drug stability in vivo was not affected by these agents. In the third study the co-administration of cimetidine had no effect on the pharmacokinetics of oral or i.v. etoposide, despite the previous observation that etoposide stability was markedly improved at pH 3-5 as compared with pH 1 in artificial gastric fluid. This series of studies, designed to investigate factors that improved etoposide stability in laboratory studies, failed to demonstrate any potentially useful improvement in AUC or bioavailability in the clinical setting.

Separation and purification of triterpene saponins from roots of Radix phytolaccae by high-speed countercurrent chromatography coupled with evaporative light scattering detection

PubMed Central

Ma, Jie; Chen, Qianliang; Lai, Daowan; Sun, Wenji; Zhang, Tianyou; Ito, Yoichiro

2009-01-01

Coupled with evaporative light scattering detection, high-speed countercurrent chromatography was successfully applied for the first time to separation and purification of four triterpene saponins including esculentoside A, B, C and D from roots of Radix Phytolaccae. The separation was performed with an optimized two-phase solvent system composed of chloroform-methanol-water (4:4:2, v/v) using the lower phase as the mobile phase at a flow rate of 1.5 ml/min,. From 150 mg of crude extract 46.3 mg of esculentoside A, 21.8 mg of esculentoside B, 7.3 mg of esculentoside C, and 13.6 mg of esculentoside D were obtained at purities of 96.7%, 99.2%, 96.5% and 97.8%, respectively, as determined by HPLC analysis. The structures of the four triterpene saponins were identified by ESI-MS,1H NMR and 13C NMR. PMID:20454595

[Pharmacokinetic and clinical studies on flomoxef in mature and premature infant].

PubMed

Tomimasu, K; Tsuji, Y; Fukuda, M; Sakai, M; Nakashita, S; Uchida, T; Mori, G; Miyazoe, H; Motoyama, K

1991-11-01

Pharmacokinetic and clinical studies of flomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below. 1. Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9 micrograms/ml and half-lives (T 1/2's) were between 0.68 and 4.89 hours. The plasma concentration of FMOX at 15 minutes after one shot intravenous injection of 40 mg/kg to 1 case was 79.9 micrograms/ml and the half-life (T 1/2) was 2.45 hours. Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0 micrograms/ml and T 1/2's were 1.64-3.41 hours. T 1/2 tended to be couse shorter as ages of babies increased. 2. Urinary excretion rates in the first 6 hours after one shot intravenous injection of FMOX 20 mg/kg to 1 case and 1-hour intravenous drip infusion of FMOX 40 mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively. 3. Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical efficacy rate was 91.7%. FMOX was also given to 6 cases for prophylaxis and prophylactic effects were observed in all the cases. 4. No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were found in 1 case. The abnormal laboratory test results were probably due to this drug.

In vitro and in vivo synergism between amoxicillin and clavulanic acid against ampicillin-resistant Haemophilus influenzae type b.

PubMed Central

Yogev, R; Melick, C; Kabat, W J

1981-01-01

Eight strans of ampicillin-resistant beta-lactamase-producing Haemophilus influenzae type b were studied in vitro for synergy between amoxicillin and clavulanic acid. The minimal inhibitory concentrations for amoxicillin alone were 6.25 to 12.5 microgram/ml, and for clavulanic acid alone they were 12.5 to 25 microgram/ml. However, seven of eight strains were inhibited by a combination of 0.36 microgram of amoxicillin and 0.36 microgram of clavulanic acid per ml. Infant rat models of bacteremia and meningitis were used to test the efficacy of amoxicillin and clavulanic acid alone and in combination upon four strains of ampicillin-resistant H. influenzae. Neither amoxicillin alone (27 animals) nor clavulanic acid alone (20 animals) sterilized the blood or cerebrospinal fluid of the animals. In contrast, 30 of 33 blood cultures and 29 of 33 cerebrospinal fluid cultures were sterile when a combination of the two drugs in the same dosages was used. The observed in vitro and in vivo synergism between amoxicillin and clavulanic acid suggests that the combination may be effective therapy for invasive infections in humans caused by ampicillin-resistant H. influenzae type b. PMID:6973952

Determination of four major saponins in the seeds of Aesculus chinensis Bunge using accelerated solvent extraction followed by high-performance liquid chromatography and electrospray-time of flight mass spectrometry.

PubMed

Chen, Junhui; Li, Wenlong; Yang, Baijuan; Guo, Xiuchun; Lee, Frank Sen-Chun; Wang, Xiaoru

2007-07-23

A new method based on accelerated solvent extraction (ASE) followed by a reliable high-performance liquid chromatography-diode array detector (HPLC-DAD) and positive ion electrospray-time of flight mass spectrometry (ESI-TOF/MS) analysis has been developed for the characterization and quantification of four major saponins in extracts of the seeds of Aesculus chinensis Bunge (semen aesculi). The saponins escin Ia, escin Ib, isoescin Ia and isoescin Ib were extracted from seeds of A. chinesis Bunge via ASE, and the operational parameters of ASE were optimized, such as extraction solvent, extraction temperature, static extraction time and extraction cycles. The optimized procedure employed 70% MeOH as extraction solvent, 120 degrees C of extraction temperature, 7 min of static extraction time, 60% flush volume and the extraction recoveries of the four compounds were nearly to 100% for two cycles. The HPLC conditions are as follows: SinoChrom ODS BP C18 (4.6 mm x 200 mm, 5 microm) column, acetonitrile and 0.10% phosphoric acid solution as mobile phase, flow rate is 1.0 mL min(-1), detection length of UV is 203 nm, injection volume is 10 microL. The results indicated that the developed HPLC method is simple, sensitive and reliable for the determination of four major saponins in seeds of A. chinesis Bunge with a good linearity (r2 > 0.9994), precision (relative standard deviation (R.S.D.) < 1.5%) and the recovery ranges of 95.2-97.3%. The limits of detection (LOD) of the four compounds were in the range of 0.40-0.75 microg mL(-1). This assay can be readily utilized as a quality control method for semen aesculi and other related medicinal plants.

[Pharmacokinetics and clinical efficacy of flomoxef in neonates].

PubMed

Azagami, S; Isohata, E; Takeda, S; Kin, Y; Oikawa, T; Osano, M; Shiro, H

1991-11-01

Clinical pharmacology and efficacy of flomoxef (FMOX) in neonates were investigated. And the following results were obtained. 1. Mean serum concentrations of FMOX at 30 minutes after administration were 24.3 micrograms/ml, 47.6 micrograms/ml, and 85.8 micrograms/ml at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg administered, respectively. 2. Mean serum half-lives of FMOX were 3.4 hours in 0-3 day-old neonates, and 2.6 hours in 4 day-old or older subjects. 3. A dose response was evident among different dose groups given 10 mg/kg, 20 mg/kg, and 40 mg/kg. 4. Urinary recovery rates of FMOX in the first 6 hours after administration ranged between 12.8 and 51.1%. 5. FMOX was effective in 7 out of 8 cases in which causative pathogens were identified. 6. Diarrhea was observed in 1 case as a side effect of the drug, but the symptom was relieved soon after the completion of the treatment. There was no case in which any abnormal laboratory results were observed. 7. FMOX has a broad spectrum of activities against Gram-positive and Gram-negative aerobes and anaerobes. It is stable against most of beta-lactamases. It was demonstrated to be highly effective in our study, and yet without any serious side effects. FMOX is therefore considered to be one of the useful agents of the first choice for the treatment of bacterial infections such as sepsis and urinary tract infections in neonates and infants.

[Epidemiologic and therapeutic study on gonorrheal infections--one shot therapy by aztreonam].

PubMed

Kumamoto, Y; Sakai, S; Tamate, H; Gohro, T; Inoke, T; Tabata, S; Tanda, H; Kato, S; Igawa, K; Tazuki, J

1985-11-01

A clinical study of a new monocyclic beta-lactam antibiotic, AZTREONAM (hereafter referred to as AZT) for gonorrheal infections as well as epidemiologic study of gonorrheal infections were made Epidemiology: There was a reflection of the increasing sexual activity of the younger generation; both male and female patients in their twenties were most frequent (male 49.5%, female 43.7%) and the percent of teen age patients was 15.1% (male) and 34.4% (female). Forty two strains (17.2%) out of 244 clinically isolated gonococci were PPNG. Residue of serious secretion was observed in a little less than 20% suggesting a complication by Chlamydia trachomatis. Clinical Result: One shot (1-2 g) therapy by AZT was given to 244 gonorrheal infection cases (212 urethritis cases of males. 32 cervicitis cases of females) with the following highly effective rate. Although beta-lactamase producing MIC of AZT at 10(6) CFU/ml showed a peak of 0.025 microgram/ml and ranged between less than 0.0125 microgram/ml to 0.2 microgram/ml. The time required for the elimination of gonococci was studied by the administration of 1 g and 2 g AZT. Gonococci became extinct in 1-8 hours or 4-4.5 hours on average. The difference between n 1 g and 2 g was scarcely observed. Clinical effect of 1 g one shot and 2 g one shot AZT was examined on the 3rd treatment day for 244 male and females cases. The effective rate was high; 90.7% by 1 g, 97.1% by 2 g for male urethritis, 100% by 1 g also by 2 g for female cervicitis. This therapeutic efficacy was kept even in PPNG, isolated cases. There were two side effects (0.8%), one case each of numbness and, redness and swelling of both hands, out of 244 cases, but both of them were minor ones without clinical complication.

[Studies of flomoxef in neonates].

PubMed

Sato, H; Narita, A; Matsumoto, K; Nakazawa, S; Suzuki, H; Nakanishi, Y; Nagao, K; Nakazawa, S; Niinou, K

1991-11-01

Studies on pharmacokinetics and clinical effects of flomoxef (FMOX), a parenteral oxacephem antibiotic, were carried out in neonates. The results obtained are summarized as follows. 1. Mean peak serum concentrations of FMOX upon single administrations at doses of 20 mg/kg and 40 mg/kg were 33.3 +/- 7.33 micrograms/ml and 68.9 micrograms/ml, respectively. 2. Mean urinary recovery rates of FMOX in the first 6 hours after administration of the above doses were 35.2% and 48.3%, respectively. 3. FMOX was administered to 4 cases including 1 prophylactic case, 1 case each with aspiration pneumonia and sepsis, hypodermic abscess of the head, and itrauterine infection, at a dose of 20-30 mg/kg 2 or 3 times a day. Clinically, excellent results were obtained in 3 cases including an methicillin-resistant Staphylococcus aureus case. 4. No side effects nor abnormal laboratory test results were observed.

[Pharmacokinetics and clinical studies on flomoxef in neonates and premature infants. A study of flomoxef in the perinatal collaboration research group].

PubMed

Fujii, R; Fujita, K; Murono, K; Saijo, M; Kakuya, F; Yoshioka, H; Maruyama, S; Sakata, H; Hiramoto, A; Inyaku, F

1993-07-01

We investigated pharmacokinetics and clinical effects of flomoxef sodium (6315-S, FMOX) in neonates and premature infants. These results are summarized as follows: 1. Pharmacokinetics (1) Plasma concentration (Ct) and half-lives (T1/2) were determined upon after intravenous one-shot injection (i.v.) of FMOX to neonates of different day-age groups (0-3 (n = 25), 4-7 (n = 18), 8-28 (n = 32) days of birth). At a dose of 10 mg/kg. i.v., mean C30 (30 minutes concentration) values were 21.2, 21.8 and 21.3 micrograms/ml, respectively, in the different groups mentioned above, and the mean T1/2 values were 3.37, 1.85 and 1.63 hours. At 20 mg/kg i.v., mean C15 (15 minutes concentration) values were 54.4, 51.4 and 50.7 micrograms/ml, and mean T1/2's were 2.99, 2.32 and 1.79 hours, respectively. At a dose of 40 mg/kg i.v., mean C15 values were 104.0, 95.9 and 99.2 micrograms/ml, and the mean T1/2's were 3.40, 1.20 and 1.80 hours, respectively. (2) Plasma concentrations and T1/2 after intravenous one-shot injection of FMOX in premature infants in group (0-3 (n = 14), 4-7 (n = 10), 8-28 (n = 13) days of birth). Mean C15's at doses of 10, 20 and 40 mg/kg in the different groups of infants were 24.0, 28.6, 21.7 and 54.0, 54.6, 55.5 and 98.2, 93.0, 106.0 micrograms/ml, and T1/2's were 4.10, 2.53, 2.57 and 4.28, 2.27, 3.02 and 4.66, 2.86, 2.09 hours, respectively. Mean Cmax values were clearly dose dependent, and mean T1/2 values tended to be longer in premature infants compared to neonates. (3) Urinary recovery rate of FMOX after intravenous injection in neonates and premature infants. Mean urinary recovery rates of FMOX in the first 6 hours after i.v. (one-shot) at doses of 10, 20 and 40 mg/kg to neonates and premature infants were 38.9-62.8% in the neonates and 30.7-61.5% in the premature infants. (4) Plasma concentrations and urinary recovery rates upon 1 hour drip infusion of 20 mg/kg in the neonate groups (or the premature infant groups) as follows: Mean C50 values were 31.0, 32.7 and 23.4 micrograms/ml, and T1/2 were 2.94, 3.68 and 2.25 hours, respectively. The recovery rates were 35.2-52.9% in the first 6 hours after administration. 2. Clinical studies The number of clinically evaluable cases in the FMOX treatment of premature infants was 199, in which the causative pathogens were identified in 71 cases (A group) and not identified in 128 cases (B group).(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of Listeria monocytogenes by fatty acids and monoglycerides.

PubMed Central

Wang, L L; Johnson, E A

1992-01-01

Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl monopalmitate were not inhibitory at 200 micrograms/ml. The bactericidal activity in brain heart infusion broth was higher at pH 5 than at pH 6. In whole milk and skim milk, K-conjugated linoleic acid was bacteriostatic and prolonged the lag phase especially at 4 degrees C. Monolaurin inactivated L. monocytogenes in skim milk at 4 degrees C, but was less inhibitory at 23 degrees C. Monolaurin did not inhibit L. monocytogenes in whole milk because of the higher fat content. Other fatty acids tested were not effective in whole or skim milk. Our results suggest that K-conjugated linoleic acids or monolaurin could be used as an inhibitory agent against L. monocytogenes in dairy foods. Images PMID:1610184

Cannabinoids impair the formation of cholesteryl ester in cultured human cells.

PubMed

Cornicelli, J A; Gilman, S R; Krom, B A; Kottke, B A

1981-01-01

The ability of cultured human fibroblasts to form cholesteryl esters from 14C-oleate is impaired by delta'-tetrahydrocannabinol, cannabidiol, and cannabinol, a group of natural products isolated from Cannabis sativa. This inhibition is compound and dose-related; 30 microM cannabidiol reduced esterification to less than 20% of the control values. The esterification of endogenous and exogenous cholesterol was affected, since inhibition was seen with either low density lipoproteins (200 micrograms/ml) or 25-hydroxycholesterol (5 micrograms/ml) as esterification stimuli. Cells treated with these compounds at doses of from 1 to 30 microM showed no impairment of protein synthesis, triglyceride or phospholipid formation, or ability to metabolize 125I-low density lipoproteins. An inhibition of cholesterol esterification was seen in human aortic medial cells. With increasing doses of these compounds, low density lipoproteins (25 micrograms/ml) became progressively less effective in suppressing HMG-CoA reductase in cultured human fibroblasts; with 30 microM cannabidiol the enzyme suppression was only 24% of that found in cells incubated with low density lipoproteins in the absence of drugs. Based on these data, we conclude that the cannabinoids "compartmentalize" cholesterol and, thus, make is unavailable for regulating cellular cholesterol metabolism. This may occur as a result of enhanced sterol efflux.

[Lead exposure in the ceramic tile industry: time trends and current exposure levels].

PubMed

Candela, S; Ferri, F; Olmi, M

1998-01-01

There is a high density of industries for the production of ceramic tiles in the District of Scandiano (province of Reggio Emilia, Emilia Romagna region). In this area, since the beginning of 1970s, the time trend of Pb exposure in ceramic tile plants has been evaluated by means of biological monitoring (BM) data collected at the Service of Prevention and Safety in the Work Environment and its associated Toxicology Laboratory. From these data, a clear decreasing time trend of exposure levels is documented, the reduction being more evident during the seventies and in 1985-88. During the seventies BM was introduced systematically in all ceramic tile plants with the determination of delta-aminolevulinic acid in urine (ALA-U). As a consequence of the BM programme, hygienic measures for the abatement of pollution inside the plants were implemented, and a reduction, from 20.6% to 2%, of ALA-U values exceeding 10 mg/l, was observed. In 1985, the determination of lead in blood (PbB) replaced that of ALA-U in the BM programmes and highlighted the persistence of high level of exposure to Pb, which could not be outlined by means of ALA-U because of its lower sensitivity. PbB levels were 36.1 micrograms/100 ml and 25.7 micrograms/100 ml in male and female workers, respectively. These results required the implementation, within the plants, of additional hygienic measures and a significant reduction of PbB was obtained in the following three years. In 1988 PbB levels were 26.0 +/- 10.7 and 21.6 +/- 10.3 micrograms/100 ml in male and female workers, respectively. In 1993-95 Pb levels were obtained from 1328 male and 771 female workers of 56 plants, accounting for about 40% of the total number of workers in the ceramic industry, in the zones of Sassuolo and Scandiano. Exposure levels are not different from those observed in the preceding years, with PbB levels of 25.3 +/- 11.1 and 19.1 +/- 9.2 micrograms/100 ml in male and female workers, respectively.

Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75.

PubMed Central

Bokser, L; Bajusz, S; Groot, K; Schally, A V

1990-01-01

Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum levels rose to 33 ng/ml 3 hr after administration and then fell gradually to approximately 3.4 ng/ml on day 16, but a second small peak was seen on day 28. Subsequently, the analog levels decreased slowly to 2.9 ng/ml on day 42. At this time, testosterone serum levels were still significantly lower than in controls. These overall results demonstrate the efficacy of SB-75 in the suppression of the pituitary-gonadal axis. This modern luteinizing hormone-releasing hormone antagonist can possibly be used for treating sex hormone-sensitive cancers and other disorders. PMID:2205853

Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75.

PubMed

Bokser, L; Bajusz, S; Groot, K; Schally, A V

1990-09-01

Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum levels rose to 33 ng/ml 3 hr after administration and then fell gradually to approximately 3.4 ng/ml on day 16, but a second small peak was seen on day 28. Subsequently, the analog levels decreased slowly to 2.9 ng/ml on day 42. At this time, testosterone serum levels were still significantly lower than in controls. These overall results demonstrate the efficacy of SB-75 in the suppression of the pituitary-gonadal axis. This modern luteinizing hormone-releasing hormone antagonist can possibly be used for treating sex hormone-sensitive cancers and other disorders.

[Effects of lidocaine on arterial and venous circulation of limbs in man].

PubMed

Edouard, A; Probst, D; Duranteau, J; Tarot, J P; Pussard, E

1991-01-01

The effects of intravenous lidocaine on limb arteries and veins were investigated in a placebo-controlled study. Seven young healthy volunteers, 23 to 28-years-old, were included. Electrocardiogram, arterial pressure and arm and leg blood flows were recorded continuously. Systolic and diastolic blood pressures were measured in the left arm by finger photoplethysmography. Limb blood flow and the limb venous system were studied by venous occlusive plethysmography. The venous parameters studied were venous tone, lowest closing pressure, venous volume at 30 mmHg, and venous distensibility. After an initial bolus of 1.5 mg.kg-1 lidocaine had been given, 30, and then 60, micrograms.kg-1.min-1 were given for one hour each. Plasma noradrenaline and serum lidocaine titres were measured before giving the lidocaine, and at the end of each one hour period. Placebo consisted in a two hour infusion of 0.25 ml.min-1 normal saline. Lidocaine titres were 1.64 +/- 0.40 microgram.ml-1 after one hour, and 2.55 +/- 0.69 microgram.ml-1 after two hours. Lidocaine increased vascular resistances in both the forearm (+81% to +93%) and the calf (+38% to +57%). There was a concomitant increase in mean arterial blood pressure (+21% to +28%) without any change in heart rate. There was a significant dose-dependent increase in plasma noradrenaline levels during the second period of the lidocaine infusion with respect to the preinfusion period and the same period during the placebo infusion. Venous capacitance measured before any infusion had been started was greater in the leg than in the arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

PubMed Central

Seabrook, G. R.; Main, M.; Bowery, B.; Wood, N.; Hill, R. G.

1992-01-01

1. The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1380375

Does gestational age affect the pharmacokinetics and pharmacodynamics of lidocaine in mother and fetus?

PubMed

Pedersen, H; Santos, A C; Morishima, H O; Finster, M; Plosker, H; Arthur, G R; Covino, B G

1988-03-01

The pharmacokinetics and pharmacodynamics of lidocaine were studied in nine chronically prepared pregnant ewes and their fetuses at a mean ( +/- SE) gestation of 119 +/- 1.0 days, and the results were compared to the data previously published for ten animals at 138 +/- 1.2 days of gestation (term 148 days). Lidocaine was infused intravenously to the mother at a constant rate of 0.1 mg.kg-1.min-1 over a period of 180 min, in order to reach a steady-state maternal plasma lidocaine concentration of approximately 2 micrograms/ml. Maternal and fetal blood samples and maternal urine were collected at intervals throughout the infusion for determination of pH, blood gases, and lidocaine concentrations. Maternal and fetal heart rate, blood pressure, and intraamniotic pressure were continuously recorded. Fetal cardiac output and organ blood flow were determined before and at the end of lidocaine infusion using radionuclide-labeled microspheres. Lidocaine tissue concentrations were determined in several maternal and fetal organs excised at the end of infusion. In both groups, the steady-state plasma concentrations of lidocaine were similar; namely, 2.3 +/- 0.17 and 2.1 +/- 0.21 micrograms/ml in preterm and term ewes, respectively. There were also no significant differences in steady-state plasma drug concentrations in preterm and term fetuses (1.3 +/- 0.11 and 1.2 +/- 0.15 micrograms/ml). The mean fetal maternal concentration ratios (F/M) were the same; namely, 0.6. Maternal urinary excretion of lidocaine correlated with urine pH, being greater in the more acid urine. Tissue uptake of drug tended to be higher in the preterm than term mothers, but only significantly so in the brain and adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)

U6 small nuclear RNA is transcribed by RNA polymerase III.

PubMed Central

Kunkel, G R; Maser, R L; Calvet, J P; Pederson, T

1986-01-01

A DNA fragment homologous to U6 small nuclear RNA was isolated from a human genomic library and sequenced. The immediate 5'-flanking region of the U6 DNA clone had significant homology with a potential mouse U6 gene, including a "TATA box" at a position 26-29 nucleotides upstream from the transcription start site. Although this sequence element is characteristic of RNA polymerase II promoters, the U6 gene also contained a polymerase III "box A" intragenic control region and a typical run of five thymines at the 3' terminus (noncoding strand). The human U6 DNA clone was accurately transcribed in a HeLa cell S100 extract lacking polymerase II activity. U6 RNA transcription in the S100 extract was resistant to alpha-amanitin at 1 microgram/ml but was completely inhibited at 200 micrograms/ml. A comparison of fingerprints of the in vitro transcript and of U6 RNA synthesized in vivo revealed sequence congruence. U6 RNA synthesis in isolated HeLa cell nuclei also displayed low sensitivity to alpha-amanitin, in contrast to U1 and U2 RNA transcription, which was inhibited greater than 90% at 1 microgram/ml. In addition, U6 RNA synthesized in isolated nuclei was efficiently immunoprecipitated by an antibody against the La antigen, a protein known to bind most other RNA polymerase III transcripts. These results establish that, in contrast to the polymerase II-directed transcription of mammalian genes for U1-U5 small nuclear RNAs, human U6 RNA is transcribed by RNA polymerase III. Images PMID:3464970

Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis.

PubMed

Li, Ning; Ma, Zhong-Jun; Chu, Yang; Wang, Ying; Li, Xian

2013-01-01

The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4μg/ml. So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure-activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly. Copyright © 2012 Elsevier B.V. All rights reserved.

[Clinical evaluation of flomoxef in neonatal infections].

PubMed

Okura, K; Yamakawa, M; Kuroki, S; Haruta, T; Kobayashi, Y

1991-11-01

Serum concentrations, urinary excretion and clinical responses of flomoxef (FMOX) were studied. The results are summarized as follows. 1. Serum concentrations of FMOX were 17.4 micrograms/ml 1-hour after intravenous injection on the average in 5 cases who received approximately 10 mg/kg, 41.8 micrograms/ml in 2 cases given 20 mg/kg, and 69.6 micrograms/ml in 2 cases given 40 mg/kg, indicating that serum concentrations of FMOX changed in a dose-dependent manner in this range. Average serum half-life (T 1/2) in 4 mature babies was 2.48 hours and that in 6 premature babies was 3.17 hours, indicating that elimination rates in premature cases tend to be slower than those in mature cases. Urinary recovery rates averaged 39.2% in the first 6 hours in 5 cases examined. 2. Five newborns or premature babies received FMOX 33.1-80.2 mg/kg (b.i.d. or t.i.d.) via intravenous route for 5 to 8 days. FMOX showed excellent or good clinical effectiveness in the treatment of all patients including 1 case each of sepsis with urinary infection, furunclal otitis, impetigo, uterogenic fetus infection and urinary infection. Bacteriological responses were also studied, and eradication of identified organisms (Escherichia coli 3 strains and Staphylococcus aureus 2 strains) was obtained upon the FMOX treatment, but in 1 strain of S. aureus showed only a decrease. No adverse reactions were observed in any cases, but a slight elevation of eosinophil was noted in 1 patient receiving a dose of 210 mg a day. From the results obtained in these tests, FMOX appears to be very usefull and safe for the treatment of some infectious diseases in neonates.

[G-CSF administration following autologous peripheral blood stem cell transplantation--the effect of G-CSF level on neutrophil recovery].

PubMed

Saigo, K; Sugimoto, T; Matsuo, M; Narita, H; Ryo, R; Kumagai, S

2000-03-01

We studied the usefulness of rhG-CSF (filgrastim) administration in patients who received autologous peripheral blood stem cell transplantation (PBSCT) combined with super-high dose chemotherapy. Twenty patients received 0-8.3 micrograms/kg/day filgrastim after PBSCT. There was a significant relationship between G-CSF dose and the neutrophil recovery rate, and the highest levels of serum G-CSF tended to correlate with neutrophil recovery rate. The highest G-CSF level after 75 micrograms injection in normal volunteers is reported to be 1,500 pg/ml. On the other hand, as one patient in our series exhibited extremely high endogenous G-CSF of 11,500 pg/ml, measurements of G-CSF might reduce the over-administration of rhG-CSF.

Modulation in vitro and in vivo of cytotoxicity but not cellular levels of doxorubicin by the calmodulin inhibitor trifluoperazine is dependent on the level of resistance.

PubMed Central

Ganapathi, R.; Schmidt, H.; Grabowski, D.; Melia, M.; Ratliff, N.

1988-01-01

The role of the calmodulin inhibitor trifluoperazine (TFP) in modulating the cellular levels and cytotoxicity in vitro and antitumour effects in vivo of doxorubicin (DOX), was evaluated in progressively DOX-resistant (5- to 40-fold) sublines of B16-BL6 mouse melanoma. In parental-sensitive B16-BL6 cells treated for 3 h, the IC50 of DOX was 0.1 microgram ml-1, and a less than 2-fold enhancement in DOX cell kill in the presence of a noncytotoxic concentration of 5 microM TFP was observed. However, in the DOX-resistant sublines, the IC50 was 0.7 to 5.0 micrograms ml-1 DOX in the absence of 5 microM TFP and 0.3 to 0.7 microgram ml-1 DOX in the presence of 5 microM TFP. The 2- to 7.5-fold decrease in the IC50 of DOX in the presence of 5 microM TFP, was dependent on the level of DOX-resistance in the various sublines. Compared to parental-sensitive cells, a 2-fold decrease in DOX-accumulation was evident only in the 40-fold DOX-resistant subline. Further, maximal enhancement (50%) of cellular DOX accumulation in the presence of 5 microM TFP was observed only in the 40-fold resistant cells treated with 5.0 micrograms ml-1 DOX. Retention of DOX in the 40-fold resistant subline was only 20% lower than similarly treated sensitive cells, and the inclusion of TFP increased DOX retention less than 10-15%. Antitumour studies in mice with experimental pulmonary metastases revealed that although DOX and DOX plus TFP had similar antitumour activity with the parental sensitive B16-BL6 cells, the combination of DOX plus TFP was significantly more effective than DOX alone with the DOX-resistant sublines. No overt toxicity was observed in normal mice treated with doses of TFP, DOX or DOX plus TFP used for in vivo chemotherapy studies. Results from this study suggest that gross cellular DOX levels do not appear to correlate with the magnitude of resistance, and the effects of TFP in modulating DOX resistance is possibly due to mechanisms other than mere alterations in cellular drug accumulation and/or retention. PMID:3179186

Extracts of spice and food plants from Thai traditional medicine inhibit the growth of the human carcinogen Helicobacter pylori.

PubMed

Bhamarapravati, S; Pendland, S L; Mahady, G B

2003-01-01

Helicobacter pylori (HP) is a gramnegative bacterium and well recognized as being the primary etiological agent responsible for the development of gastritis, dyspepsia, peptic ulcer disease and gastric cancer. In developing countries, a high prevalence of HP infection is associated with an increased incidence of gastric cancer. Thailand, however, while having a high prevalence of HP infections, has a lower than expected gastric cancer rate than other developing countries. It has been suggested that the diet and life style in Thailand may explain this discrepancy. The in vitro susceptibility of 18 strains of HP to 20 extracts of spice and food plants used in Thai traditional medicine for the treatment of GI disorders was assessed. Methanol extracts of Myristica fragrans (aril) inhibited the growth of all HP strains with minimum inhibitory concentration (MIC) of 12.5 micrograms/ml; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had an MIC of 25.0 micrograms/ml; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50.0 micrograms/ml. Extracts with an MIC of 100.0 micrograms/ml included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf). Plants used in Thai traditional medicine to treat gastrointestinal ailments inhibit the growth of HP. These data indicate that these plants may have chemopreventative activities and thus may partly explain the reduced incidence of gastric cancer in Thailand.

Effects of amitriptyline and clomipramine in the isolated, perfused rabbit heart.

PubMed

Nielsen-Kudsk, F; Quist, S

1980-04-01

The cardiac effects of supratherapeutic concentrations of two tricyclic antidepressants were studied in isolated rabbit hearts, which were perfused with a modified Krebs-Henseleit solution containing 0.25 or 0.50 micrograms ml-1 of amitriptyline or 0.28 micrograms mg-1 of clomipramine. The following parameters were continuously recorded:heart rate, amplitude and rate of contraction, coronary flow rate, myocardial oxygen consumption and ECG. The lowest concentration of amitriptyline caused a time correlated decrease (20%) in the frequency of spontaneous beating and a pronounced decrease in the amplitude (62%) and rate of cardiac contraction (58%). Maximum increases of the PQ-interval of about 46% and of the QRS-complex of about 100% were observed. At the higher amitriptyline concentration these effect further increased. Clomipramine 0.28 micrograms ml-1 also had a very pronounced and time correlated negative inotropic effect, but the effects upon the conduction velocities were substantially lesser than those produced by the equimilar concentration of amitriptyline. The compounds caused only insignificant changes in coronary flow. The oxygen consumption did not decrease in proportion to the decrease in contractility, as an expression of decreased myocardial efficiency. The effects of the drugs are discussed in relation to theri myocardial accumulation pharmacokinetics and influence upon the membraneous sodium and calcium flux and intracellular metabolism.

[PREPARATION OF HUMAN TISSUE PROTEIN EXTRACTS ENRICHED WITH THE SPHINGOMYELIN SYNTHASE 1].

PubMed

Sudarkina, O Yu; Dergunova, L V

2015-01-01

Sphingomyelin synthase 1 (SMS 1) catalyzes sphingomyelin biosynthesis in eukaryotic cells. We previously studied the structure of the human SGMS1 gene, which encodes the enzyme and its numerous transcripts. The tissue-specific expression of the transcripts was also described. Analysis of the SMS1 protein expression in human tissues using immunoblotting of tissue extracts prepared in the RIPA (Radio Immuno-Precipitation Assay) buffer revealed a weak signal in renal cortex, testis, lung, and no signal in placenta and lymphatic node. In this work, a new method of preparation of the tissue protein extracts enriched with SMS1 was suggested. The method based on the consecutive extraction with a buffer containing 0.05 and 1 mg/ml of the Quillaja saponaria saponin allowed SMS1 to be detected in all tissues tested. The SMS1 content in the saponin extract of kidney cortex is about 12-fold higher compared to the RIPA extraction procedure.

Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

PubMed Central

Bodhidatta, L; Taylor, D N; Chitwarakorn, A; Kuvanont, K; Echeverria, P

1988-01-01

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand. PMID:3293526

Simultaneous quantification of five steroid saponins from Dioscorea zingiberensis C.H.Wright in rat plasma by HPLC-MS/MS and its application to the pharmacokinetic studies

PubMed Central

Zhang, Xinxin; Li, Jing; Ito, Yoichiro; Sun, Wenji

2014-01-01

A simple, reliable and sensitive high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was established for simultaneous analyses of the following 5 steroid saponins in rat plasma after the single dose administration of total steroid saponins extracted from the rhizome of Dioscorea zingiberensis C.H.Wright for the first time. Protodioscin, huangjiangsu A, zingiberensis new saponin, dioscin, and gracillin were quantified using ginsenoside Rb1 as the internal standard (IS). The plasma samples were pretreated by a single step acetonitrile-mediated protein precipitation. The chromatographic separation was performed on an Inersil ODS-3 C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase composed of acetonitrile and water containing 0.1% formic acid under a gradient elution mode at 0.2 mL min−1 using a microsplit after the eluent from the HPLC apparatus. The quantification was accomplished on a triple quadrupole tandem mass spectrometer using the multiple reaction monitoring (MRM) in the positive ionization mode. The above five analytes were stable under sample storage and preparation conditions applied in the present study. The linearity, precision, accuracy, and recoveries of the analysis confirmed the requirements for quality-control purposes. After validation, this proposed method was successfully adopted to investigate the pharmacokinetic parameters of these five analytes. PMID:25201262

Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis.

PubMed Central

Murphy, M; Bernard, E M; Ishimaru, T; Armstrong, D

1997-01-01

Voriconazole, a new azole antifungal agent, showed potent activity against clinical isolates of Aspergillus spp. in vitro. For A. fumigatus, the MIC range was < 0.03 to 0.5 microgram/ml and the MIC at which 90% of isolates are inhibited was 0.25 microgram/ml. In an experimental model of invasive pulmonary aspergillosis which mimics infection in humans, oral voriconazole at dosages of 30 mg/kg of body weight per day significantly delayed or prevented mortality. PMID:9056016

Phytochemical analysis and antibacterial activities extracts of mangrove leaf against the growth of some pathogenic bacteria.

PubMed

Alizadeh Behbahani, Behrooz; Tabatabaei Yazdi, Farideh; Shahidi, Fakhri; Noorbakhsh, Hamid; Vasiee, Alireza; Alghooneh, Ali

2018-01-01

In this study, the effects of water, ethanol, methanol and glycerin at five levels (0, 31.25, 83.33, 125 and 250 ml) were investigated on the efficiency of mangrove leaf extraction using mixture optimal design. The antimicrobial effect of the extracts on Streptococcus pneumoniae, Enterococcus faecium and Klebsiella pneumoniae was evaluated using disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. The mangrove leaf extraction components were identified through gas chromatography/mass spectrometry (GC/MS). Phytochemical analysis (alkaloids, tannins, saponins, flavone and glycosides) were evaluated based on qualitative methods. Antioxidant activity of extracts was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) methods. Maximum antimicrobial effect was observed in Enterococcus faecium and highest resistance against mangrove leaf extract in Enterococcus faecium and Klebsiella pneumoniae, respectively. Increasing concentration of mangrove extracts had a significant effect (p ≤ 0.05) on inhibition zone diameter. The MICs of the mangrove leaf extraction varied from 4 mg/ml to 16 mg/ml. The optimum formulation was found to contain glycerin (0 ml), water (28.22 ml), methanol (59.83 ml) and ethanol (161.95 ml). The results showed that the highest antioxidant activity was related to optimum extract of mangrove leaf and ethanolic extract respectively. The results of phytochemical screening of Avicennia marina leaves extract showed the existence of alkaloids, tannins, saponins, flavone and glycosides. 2-Propenoic acid, 3-phenyl- was the major compound of Avicennia marina. The results of non-significant lack of fit tests, and F value (14.62) indicated that the model was sufficiently accurate. In addition, the coefficient of variations (16.8%) showed an acceptable reproducibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

Saponins extracted from by-product of Asparagus officinalis L. suppress tumour cell migration and invasion through targeting Rho GTPase signalling pathway.

PubMed

Wang, Jieqiong; Liu, Yali; Zhao, Jingjing; Zhang, Wen; Pang, Xiufeng

2013-04-01

The inedible bottom part (~30-40%) of asparagus (Asparagus officinalis L.) spears is usually discarded as waste. However, since this by-product has been reported to be rich in many bioactive phytochemicals, it might be utilisable as a supplement in foods or natural drugs for its therapeutic effects. In this study it was identifed that saponins from old stems of asparagus (SSA) exerted potential inhibitory activity on tumour growth and metastasis. SSA suppressed cell viability of breast, colon and pancreatic cancers in a concentration-dependent manner, with half-maximum inhibitory concentrations ranging from 809.42 to 1829.96 µg mL(-1). However, SSA was more functional in blocking cell migration and invasion as compared with its cytotoxic effect, with an effective inhibitory concentration of 400 µg mL(-1). A mechanistic study showed that SSA markedly increased the activities of Cdc42 and Rac1 and decreased the activity of RhoA in cancer cells. SSA inhibits tumour cell motility through modulating the Rho GTPase signalling pathway, suggesting a promising use of SSA as a supplement in healthcare foods and natural drugs for cancer prevention and treatment. © 2012 Society of Chemical Industry.

Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2.

PubMed Central

Landucci, E C; Antunes, E; Donato, J L; Faro, R; Hyslop, S; Marangoni, S; Oliveira, B; Cirino, G; de Nucci, G

1995-01-01

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7537590

Evaluation of African medicinal plants for their in vitro trypanocidal activity.

PubMed

Freiburghaus, F; Kaminsky, R; Nkunya, M H; Brun, R

1996-12-01

Petroleum ether, dichloromethane, methanol and water extracts from 24 plants, belonging to 19 families, which are reported in the literature as traditional remedies for sleeping sickness (human African trypanosomiasis) were screened for in vitro activity against Trypanosoma brucei rhodesiense, as well as fro cytotoxicity for a human fibroblast cell-line (WI-38). The trypanocidal activity of the natural compounds berberine and harmane, both documented as being trypanocidal, was also evaluated. Promising trypanocidal activity with IC50 values below 10 micrograms/ml was found in 32 extracts of 13 plant species. The most active extracts with IC50 below 1 microgram/ml were derived from Annona senegalensis, Bussea occidentalis and Physalis angulata. The plant extracts showed a modest selectivity index, in contrast to commercially available trypanocides which have a more distinct selective toxicity against trypanosomes.

Reduction of Brochothrix thermosphacta on beef surfaces following immobilization of nisin in calcium alginate gels.

PubMed

Cutter, C N; Siragusa, G R

1996-07-01

Lean and adipose beef carcass tissues inoculated with Brochothrix thermosphacta (BT) (approx. 4.50 log10 cfu cm-2) were left untreated (U) or treated with 100 micrograms ml-1 nisin (N), calcium alginate (A) or 100 micrograms ml-1 nisin immobilized in a calcium alginate gel (AN). Tissue samples were refrigerated after treatments and bacterial populations and nisin activity were determined at 0, 1, 2 and 7 d. U, A and N treatments of lean and adipose tissues did not suppress bacterial growth ( > 6 log10 cfu cm-2 by day 7) while treatments of lean and adipose tissues with AN suppressed bacteria ( > 2.42 log10 cfu cm-2 by day 7). Bacteriocin titres from both tissues were higher in AN vs N samples after the 7 d incubation. This study demonstrates that immobilization of nisin in a gel may be a more effective delivery system of a bacteriocin to the carcass surface than direct application.

Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

PubMed

Berisha, H; Foda, H; Sakakibara, H; Trotz, M; Pakbaz, H; Said, S I

1990-08-01

Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

Quantitative analysis of flavonoids, alkaloids and saponins of Banxia Xiexin decoction using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

PubMed

Wang, Ying; Xu, Ranchi; Xiao, Juan; Zhang, Jian; Wang, Xinhong; An, Rui; Ma, Yueming

2014-01-01

Banxia Xiexin decoction (BXD) is an effective Chinese Medicinal Prescription in treating gastroenteritis diseases. In this study an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to separate and determine 18 major active ingredients of BXD in order to guarantee quality. The separation of ten flavonoids, four alkaloids and four saponins was accomplished on an Acquity BEH C18 (2.1mm×100mm, 1.7μm) column using gradient elution with 0.1% (v/v) formic acid water (A) and 0.1% (v/v) formic acid in methanol (B). All the analytes were detected in positive electrospray ionization tandem mass spectrometry by selective reaction monitoring (SRM) mode. A good linear regression relationship for each analyte was obtained over the range from 2.41-438ng/ml to 20.75-4150ng/ml. The precision was evaluated by intra- and inter-day assays with relative standard deviation (RSD) less than 7.7%. The recovery measured at three concentration levels varied from 92.4% to 107.8%. The method sensitivity expressed as LOQ was typically 0.97-4.15ng/ml. The assay was successfully applied for determination of the 18 bioactive compounds in BXD. The results indicated that the new UPLC-MS/MS method was rapid and accurate, and could be reliably utilized as a quality control method for BXD. Copyright © 2013 Elsevier B.V. All rights reserved.

Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramp, W.K.; Lenz, L.G.; Galvin, R.J.

1991-05-01

Use of smokeless tobacco is associated with various oral lesions including periodontal damage and alveolar bone loss. This study was performed to test the effects of nicotine on bone-forming cells at concentrations that occur in the saliva of smokeless tobacco users. Confluent cultures of osteoblast-like cells isolated from chick embryo calvariae were incubated for 2 days with nicotine added to the culture medium (25-600 micrograms/ml). Nicotine inhibited alkaline phosphatase in the cell layer and released to the medium, whereas glycolysis (as indexed by lactate production) was unaffected or slightly elevated. The effects on medium and cell layer alkaline phosphatase weremore » concentration dependent with maximal inhibition occurring at 600 micrograms nicotine/ml. Nicotine essentially did not affect the noncollagenous protein content of the cell layer, but did inhibit collagen synthesis (hydroxylation of ({sup 3}H)proline and collagenase-digestible protein) at 100, 300, and 600 micrograms/ml. Release of ({sup 3}H)hydroxyproline to the medium was also decreased in a dose-dependent manner, as was the collagenase-digestible protein for both the medium and cell layer. In contrast, DNA synthesis (incorporation of ({sup 3}H)thymidine) was more than doubled by the alkaloid, whereas total DNA content was slightly inhibited at 600 micrograms/ml, suggesting stimulated cell turnover. Morphologic changes occurred in nicotine-treated cells including rounding up, detachment, and the occurrence of numerous large vacuoles. These results suggest that steps to reduce the salivary concentration of nicotine in smokeless tobacco users might diminish damaging effects of this product on alveolar bone.« less

Ginsenoside Re and notoginsenoside R1: Immunologic adjuvants with low haemolytic effect.

PubMed

Sun, Hong-Xiang; Chen, Yuehua; Ye, Yiping

2006-07-01

The further purification of the total saponins from the roots of Panax notoginseng (Burk.) F. H. Chen by ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afforded two adjuvant active dammarane-type saponins, ginsenoside Re (1) and notoginsenoside R1 (2). These two saponins were evaluated for haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The concentrations inducing 50% of the maximum haemolysis (HD50), using 0.5% red blood cell suspensions, were 469.6+/-16.9 and 420.4+/-22.9 microg/ml for 1 and 2, respectively. Compounds 1 and 2 significantly increased the concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific IgG, IgG1, and IgG2b antibody titres in serum were also significantly enhanced by 1 and 2 compared with OVA control group (P<0.05, P<0.01, or P<0.001). The results indicate that 1 and 2 showed a slight haemolytic activity and significant adjuvant effect on specific antibody and cellular immune response against OVA in mice, and that the type of the terminal sugar of the sugar chain at C(6) of protopanaxatriol could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure-function relationship might be useful for developing semisynthetic dammarane-type saponin derivatives with immunological adjuvant activity.

In vitro comparison of the activity of various antibiotics and drugs against new Taiwan isolates and standard strains of avian mycoplasma.

PubMed

Lin, M Y

1987-01-01

Twenty-nine antibiotics or drugs were incorporated individually into mycoplasma agar to evaluate their inhibitory activity against avian mycoplasmas: 100 recent Taiwan isolates of 7 serotypes and 10 standard strains of 7 serotypes were tested. All of the standard strains were very sensitive to erythromycin, chlorotetracycline, doxycycline, minocycline, and tetracycline, but the local isolates were highly resistant to these antibiotics. The drugs or antibiotics that possessed an MIC90 of 50 micrograms/ml or less against the local isolates were tiamulin (less than 0.4 micrograms/ml), lincospectin (2.7), josamycin (2.7), lincomycin (3.0), spectinomycin (4.8), tylosin (6.0), kanamycin (6.0), chloramphenicol (6.0), gentamicin (7.5), apramycin (24.5), doxycycline (27.4), minocycline (29.0), spiramycin (30.0), colistin (44.3), leucomycin (45.0), and streptomycin (50.0). The MIC90 of the other antibiotics or drugs was greater than 50 micrograms/ml. None of the isolates or strains were sensitive to nalidixic acid, ronidazole, penicillin, ampicillin, cephalexin, carbadox, or four sulfa drugs at a concentration about 5 times the therapeutic level.

[The isolation and characteristics of mutants of the Saccharopolyspora erythraea strain resistant to thiostrepton].

PubMed

Nastasiak, I N; Fedorenko, V A; Danilenko, V N

1997-01-01

The formation of thiostreptone resistant spontaneous and nitrosoguanidine-induced mutants in the erythromycin-producing organism Saccharopolyspora erythraea was investigated. The investigated collection of the mutants was heterogeneous by the level of the thiostreptone resistance (2.5 to 20 micrograms/ml). The thiostreptone resistance mutations had a pleiotropic effect: 17 per cent of the mutants was characterized by the growth thermosensitivity and 26 and 5.8 per cent of the mutants were characterized by loss of the ability to form melanine and aerial mycelium respectively. Such phenotypes were most frequent in the mutants resistant to low concentrations of thiostreptone (2 to 5 micrograms/ml). The absolute majority of the isolated thiostreptone resistant mutants was unstable and formed both the antibiotic resistant and the antibiotic sensitive clones. The greatest portion of the strains with high antibiotic activity (20 per cent) was detected among the S. erythraea spontaneous mutants on the medium with 2.5 micrograms/ ml of thiostreptone. It was shown that the instability of the high antibiotic activity in the mutants was associated with loss of the thiostreptone resistance property.

Effects of extracellular matrices and growth factors on the development of isolated porcine blastomeres.

PubMed

Saito, S; Niemann, H

1991-05-01

The effects of extracellular matrices and growth factors on the development of isolated blastomeres derived from intact 4-, 8-, and 16-cell porcine embryos (termed, respectively, 1/4, 1/8, and 1/16 blastomeres) were investigated in vitro and in vivo. Blastomeres were incubated in extracellular matrix components fibronectin (FIN) or swine skin gelatin (SSG)-precoated culture dishes containing either modified Krebs' Ringer Bicarbonate solution (mKRB) supplemented with 10% heat-inactivated lamb serum, or Hanks' solution supplemented with 10% heat-inactivated newborn calf serum (NBCS) or Waymouth medium supplemented with 10% NBCS or in noncoated dishes in mKRB supplemented with either insulin (10, 100, or 1,000 micrograms/ml), transferrin (10, 100, or 1,000 micrograms/ml), or cAMP (0.2 or 2.0 micrograms/ml). Cultures observed at 24-h intervals and morphological development was recorded. Blastomeres were classified into three categories according to their morphology: (1) regular blastocysts, (2) trophectodermal vesicles, or (3) no development. After 96 h, culture was determined; the overall diameter of the blastocysts was determined and the nuclei were counted. Blastomeres/blastocysts did not adhere to the bottom of the culture dishes coated with extracellular matrices. Blastocyst formation rate was highest when FIN/mKRB was used and reached 44.3%, 41.8%, and 36.5% for 1/4, 1/8, and 1/16 blastomeres, respectively. The respective blastocysts contained an average of 31.2 +/- 5.8, 58.2 +/- 8.4, and 18.5 +/- 3.5 nuclei and had an overall diameter of 250.0 +/- 10.1, 235.0 +/- 12.8, and 172.5 +/- 13.7 microns, 1/8 blastomeres displayed a better (p less than 0.05) growth rate than 1/4 and 1/16 blastomeres, and 1/8 blastomeres in FIN/mKRB grew better (p less than 0.01) when cultured in an open system than in a microdrop under oil (35.5% vs. 5.0% blastocysts). Neither cAMP nor transferrin had a significant stimulating effect on blastocyst development of 1/8 blastomeres when mKRB plus serum was used as the medium. Insulin supplementation (10 or 100 micrograms/ml) to mKRB plus lamb serum significantly (p less than 0.05) stimulated blastocyst formation rate compared with controls (58.6% and 38.9% vs. 17.7%, respectively; 32.6 +/- 2.5, 58.5 +/- 11.8, and 45.1 +/- 4.6 nuclei, respectively). Transfer of 457 blastocysts grown for 24 h in FIN/mKRB to 16 recipients gilts led to three pregnancies, and two litters were born from 1/8 blastomere-derived blastocysts following 116 days of gestation.4+ is

Gingival fibroblasts degrade type I collagen films when stimulated with tumor necrosis factor and interleukin 1: evidence that breakdown is mediated by metalloproteinases.

PubMed

Meikle, M C; Atkinson, S J; Ward, R V; Murphy, G; Reynolds, J J

1989-05-01

We previously suggested that periodontal pathogens might mediate connective tissue degradation in periodontal diseases through the ability of antigens from their cell walls to stimulate cytokine production by circulating mononuclear cells. Such cytokines would then induce metalloproteinase (MP) synthesis by resident gingival cells and thus initiate matrix degradation. In the present investigation human gingival fibroblasts (HGFs) were grown on [14C]-labelled type I collagen films and stimulated with either tumor necrosis factor (TNF) or interleukin-1 (IL-1) for 48 h. Collagenolysis occurred in a dose-dependent manner; the optimal dose for human rTNF alpha was 100 ng/ml and for rIL-1 alpha and rIL-1 beta, 1 ng/ml. Collagen degradation was accompanied by increased synthesis and release of the MPs collagenase, gelatinase and stromelysin, and there was a reduction in free TIMP (tissue inhibitor of metalloproteinases): collagenase and stromelysin were detected in both active and latent forms. Cytokine-stimulated collagenolysis was abolished by the addition of exogenous human rTIMP (5 units/ml). We also measured collagenase and TIMP by ELISAs which recognize all forms of collagenase (latent, active or complexed) and TIMP (free or complexed). These showed that while collagenase activity (0.6-1.2 microgram/ml) correlated with lysis, total TIMP levels remained unchanged at approximately 0.2 microgram/ml. These results demonstrate important roles for MPs and TIMP in regulating type I collagen degradation by HGFs, and support the hypothesis that connective tissue destruction during inflammatory diseases may be initiated, at least in part, by TNF and IL-1.

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

PubMed

Reddy, B S; Furuya, K; Lowenfels, A

1984-07-01

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Chlorhexidine susceptibilities of mutans streptococcal serotypes and ribotypes.

PubMed

Grönroos, L; Mättö, J; Saarela, M; Luoma, A R; Luoma, H; Jousimies-Somer, H; Pyhälä, L; Asikainen, S; Alaluusua, S

1995-04-01

The susceptibilities of 379 clinical mutans streptococcal isolates to chlorhexidine (CHX) were tested by agar dilution according to the standards of the National Committee for Clinical Laboratory Standards. Isolates were obtained from saliva samples of 34 young mothers who had high or moderate salivary levels of mutans streptococci at baseline. Samples were collected on three occasions, before childbirth, when each child was 6 months old, and 1 year later. Of these isolates, 50% were inhibited at 1 microgram of CHX per ml, 90% were inhibited at 2.0 micrograms/ml, and all were inhibited at 4.0 micrograms/ml. The MICs for Streptococcus mutans isolates (serotypes c, e, and f) were lower than those for Streptococcus sobrinus isolates (serotypes d and g). In some subjects, the MICs for isolates of the same serotype were different. This phenomenon was studied by ribotyping isolates (n = 45) from selected subjects (n = 7). It was found that if there were intraindividual differences in the MICs for isolates of the same serotype, then the ribotypes of these isolates were different. In order to decrease the mutans streptococcal infection risk for children, 24 mothers (test group) brushed their teeth periodically with a gel that contained 0.3% CHX digluconate and 0.2% NaF, pH 5.8, between the second and third sampling occasions. The gel was used twice a day for the first 10 days of each month. Development of resistant strains during CHX-NaF gel use was not detected. The serotype distribution of isolates from the test group after 1 year of periodic CHX-NaF gel use did not differ from that at baseline. Periodic CHX-NaF gel brushing did not lead to lower salivary mutans streptococcal counts.

In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity.

PubMed Central

Andries, K; Dewindt, B; Snoeks, J; Willebrords, R; van Eemeren, K; Stokbroekx, R; Janssen, P A

1992-01-01

Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds. Although its predecessor, R 61837, a substituted phenyl-pyridazinamine, was effective in inhibiting 80% of 100 serotypes tested (EC80) at concentrations above 32 micrograms/ml, pirodavir inhibits the same percentage of viruses at 0.064 micrograms/ml. Whereas R 61837 was active almost exclusively against rhinovirus serotypes of antiviral group B, pirodavir is broad spectrum in that it is highly active against both group A and group B rhinovirus serotypes. Pirodavir is also effective in inhibiting 16 enteroviruses, with an EC80 of 1.3 micrograms/ml. Susceptible rhinovirus serotypes were rendered noninfectious by direct contact with the antiviral compound. Their infectivity was not restored by dilution of virus-drug complexes, but was regained by organic solvent extraction of the compound for most serotypes. Neutralized viruses became stabilized to acid and heat, strongly suggesting a direct interaction of the compounds with viral capsid proteins. Mutants resistant to R 61837 (up to 85 times the MIC) were shown to bear some cross-resistance (up to 23 times the MIC) to the new compound, indicating that pirodavir also binds into the hydrophobic pocket beneath the canyon floor of rhinoviruses. Pirodavir acts at an early stage of the viral replication cycle (up to 40 min after infection) and reduces the yield of selected rhinoviruses 1,000- to 100,000-fold in a single round of replication. The mode of action appears to be serotype specific, since pirodavir was able to inhibit the adsorption of human rhinovirus 9 but not that of human rhinovirus 1A. Pirodavir is a novel capsid-binding antipicornavirus agent with potent in vitro activity against both group A and group B rhinovirus serotypes. PMID:1317142

Chlorhexidine susceptibilities of mutans streptococcal serotypes and ribotypes.

PubMed Central

Grönroos, L; Mättö, J; Saarela, M; Luoma, A R; Luoma, H; Jousimies-Somer, H; Pyhälä, L; Asikainen, S; Alaluusua, S

1995-01-01

The susceptibilities of 379 clinical mutans streptococcal isolates to chlorhexidine (CHX) were tested by agar dilution according to the standards of the National Committee for Clinical Laboratory Standards. Isolates were obtained from saliva samples of 34 young mothers who had high or moderate salivary levels of mutans streptococci at baseline. Samples were collected on three occasions, before childbirth, when each child was 6 months old, and 1 year later. Of these isolates, 50% were inhibited at 1 microgram of CHX per ml, 90% were inhibited at 2.0 micrograms/ml, and all were inhibited at 4.0 micrograms/ml. The MICs for Streptococcus mutans isolates (serotypes c, e, and f) were lower than those for Streptococcus sobrinus isolates (serotypes d and g). In some subjects, the MICs for isolates of the same serotype were different. This phenomenon was studied by ribotyping isolates (n = 45) from selected subjects (n = 7). It was found that if there were intraindividual differences in the MICs for isolates of the same serotype, then the ribotypes of these isolates were different. In order to decrease the mutans streptococcal infection risk for children, 24 mothers (test group) brushed their teeth periodically with a gel that contained 0.3% CHX digluconate and 0.2% NaF, pH 5.8, between the second and third sampling occasions. The gel was used twice a day for the first 10 days of each month. Development of resistant strains during CHX-NaF gel use was not detected. The serotype distribution of isolates from the test group after 1 year of periodic CHX-NaF gel use did not differ from that at baseline. Periodic CHX-NaF gel brushing did not lead to lower salivary mutans streptococcal counts. PMID:7785991

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

PubMed

Giustina, A; Schettino, M; Bussi, A R; Legati, F; Licini, M; Zuccato, F; Wehrenberg, W B

1992-01-01

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.

Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges.

PubMed Central

Bakken, J S; Bruun, J N; Gaustad, P; Tasker, T C

1986-01-01

A single intravenous dose of 2.0 g of amoxicillin and 0.2 g of potassium clavulanate was given to patients with bacterial meningitis, and the pharmacokinetics of both drugs in the cerebrospinal fluid (CSF) and plasma were evaluated. Twenty-one patients aged 14 to 76 years were studied. Both amoxicillin and potassium clavulanate were detectable in the CSF as early as 1 h and reached peak concentrations by approximately 2 h. The highest mean CSF concentrations were 2.25 micrograms/ml for amoxicillin and 0.25 micrograms/ml for potassium clavulanate and were found in patients with moderately or severely inflamed meninges. The CSF penetration relative to plasma for amoxicillin and potassium clavulanate was 5.8 and 8.4%, respectively. These levels suggest that the amoxicillin-potassium clavulanate combination may be effective for the treatment of bacterial meningitis caused by beta-lactamase-producing pathogens. PMID:3777911

Synthesis of acid-soluble spore proteins by Bacillus subtilis.

PubMed

Leventhal, J M; Chambliss, G H

1982-12-01

The major acid-soluble spore proteins (ASSPs) of Bacillus subtilis were detected by immunoprecipitation of radioactively labeled in vitro- and in vivo-synthesized proteins. ASSP synthesis in vivo began 2 h after the initiation of sporulation (t2) and reached its maximum rate at t7. This corresponded to the time of synthesis of mRNA that stimulated the maximum rate of ASSP synthesis in vitro. Under the set of conditions used in these experiments, protease synthesis began near t0, alkaline phosphatase synthesis began at about t2, and refractile spores were first observed between t7 and t8. In vivo- and in vitro-synthesized ASSPs comigrated in sodium dodecyl sulfate-polyacrylamide gels. Their molecular weights were 4,600 (alpha and beta) and 11,000 (gamma). The average half-life of the ASSP messages was 11 min when either rifampin (10 micrograms/ml) or actinomycin D (1 microgram/ml) was used to inhibit RNA synthesis.

[Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period].

PubMed

Makinoda, S; Tsuruta, H; Iwaki, M; Negishi, H; Hanatani, K; Tanaka, T; Fujimoto, S

1991-06-01

Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram-negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study.

Effect of antiischemic therapy on coronary flow reserve and the pressure-maximal coronary flow relationship in anesthetized swine.

PubMed

McFalls, E O; Duncker, D J; Sassen, L M; Gho, B C; Verdouw, P D

1991-12-01

The effect of nifedipine (0.5, 1.0, and 2.0 micrograms/kg/min), metoprolol (0.1, 0.5, and 1.0 mg/kg), the beta 1-selective adrenoceptor partial agonist epanolol (10, 50, and 200 micrograms/kg), or equivalent volumes of isotonic saline (n = 6, in each group), on coronary blood flow capacity were studied in anesthetized swine. Intracoronary bolus injections of adenosine (20 micrograms/kg/0.2 ml) were administered without and during three levels of coronary stenosis, prior to and following each dose of drug, to obtain maximal coronary blood flows at different perfusion pressures in the autoregulatory range. Coronary perfusion pressures were varied by partial inflation of a balloon around the left anterior descending coronary artery. Special care was taken that the stenoses not lead to myocardial ischemia. Three indices of coronary blood flow capacity were used: absolute coronary flow reserve (ACFR, the ratio of maximal to resting coronary blood flow), the slope and the extrapolated pressure at zero flow (Pzf) of the pressure-maximal coronary flow (PMCF) relationship, and relative coronary flow reserve (RCFR, the ratio of maximal coronary blood flow with a stenosis to maximal coronary blood flow without a stenosis) at two of the three levels of stenosis. Nifedipine decreased ACFR from 4.5 +/- 1.9 to 1.9 +/- 0.3 (mean +/- SD; p less than 0.05), reflecting in part the increase in resting coronary blood flow. The nifedipine-induced changes in maximal coronary blood flow were not only due to a drop in perfusion pressure, as the slope of the PMCF relationship decreased from 2.27 +/- 0.49 ml/(min.mm Hg) to 1.54 +/- 0.51 ml/(min.mm Hg) (p less than 0.05), and Pzf decreased from 30 +/- 4 mm Hg to 20 +/- 7 mm Hg (p less than 0.05). Consequently, calculated maximal coronary blood flow was attenuated from 114 +/- 31 ml/min to 93 +/- 37 ml/min at 80 mm Hg, but was enhanced from 23 +/- 13 to 37 +/- 24 ml/min at 40 mm Hg coronary perfusion pressure. In concert with the change in the PMCF relationship, RCFR at equivalent severe stenosis increased from 0.33 +/- 0.06 to 0.47 +/- 0.10 (p less than 0.05). No changes were observed with metoprolol, epanolol, or saline. The effect of nifedipine on the PMCF relationship not only provides a mechanism for the drug's antiischemic action, but should also be considered in the interpretation of coronary flow reserve measurements in patients on nifedipine treatment.

Absorption and subjective effects of caffeine from coffee, cola and capsules.

PubMed

Liguori, A; Hughes, J R; Grass, J A

1997-11-01

Coffee is often perceived as producing greater pharmacological effects than cola. The present study compared the magnitude and rapidity of peak caffeine levels and subjective effects between coffee and cola. Thirteen users of both coffee and cola (mean daily caffeine consumption = 456 mg) ingested 400 mg caffeine via 12 oz unsweetened coffee, 24 oz sugar-free cola or 2 capsules in a random, double-blind, placebo-controlled, within-subjects design. Subjects provided a saliva sample and completed subjective effect scales 15 min before and 30, 60, 90, 120, 180 and 240 min after ingestion. Mean peak saliva caffeine levels did not differ between coffee (9.7 +/- 1.2 micrograms/ml) and cola (9.8 +/- 0.9 micrograms/ml) and appeared to be greater with these beverages than with the capsule (7.8 +/- 0.6 micrograms/ml; p = NS). Saliva caffeine levels peaked at similar times for coffee (42 +/- 5 min) and cola (39 +/- 5 min) but later for capsule (67 +/- 7 min; p = 0.004). There was no main effect of vehicle or interaction of vehicle and drug on magnitude of peak effect or time to peak increase on self-report scales. In summary, peak caffeine absorption, time to peak absorption, and subjective effects do not appear to be influenced by cola vs. coffee vehicle. Perceived differences in the effects of coffee vs. cola may be due to differences in dose, time of day, added sweetener, environmental setting or contingencies.

Inhibition of cell growth by a hypothalamic peptide.

PubMed Central

Redding, T W; Schally, A V

1982-01-01

A fraction purified from acetic acid extracts of porcine hypothalami was found to contain significant antimitogenic activity when tested in normal and neoplastic cell lines. Addition of this hypothalamic material (1-100 micrograms/ml) to culture media significantly inhibited [3H]thymidine incorporation into cellular DNA in several cell lines. Amino acid incorporation into pituitary proteins and uridine incorporation into RNA were also significantly reduced by this factor(s). Addition to the culture media of this hypothalamic material at 5 micrograms/ml and 50 micrograms/ml per day decreased by 17% and 36%, respectively, cell numbers of 3T6 fibroblast cell cultures. Time-response curves showed that the inhibition of [3H]thymidine incorporation into DNA in 3T6 fibroblast cells begins within 2 hr after adding this fraction to the culture medium. The inhibitory action cannot be explained by a direct cytotoxic effect since 3T6 cells labeled with 51Cr and incubated for 6 hr in the presence of this hypothalamic fraction fail to show an increase in the release of 51Cr into the medium as compared with controls. Incubation with trypsin and chymotrypsin completely abolished the antimitogenic activity of this material and pepsin decreased it. This strongly suggests that the antimitogenic activity exhibited by this fraction is due to a polypeptide(s). These observations provide evidence for the presence in the mammalian hypothalamus of an antimitogenic peptide(s) that may be involved in the regulation of cell proliferation. PMID:6757925

[Effect of lysine clonixinate and indomethacin on lipoxygenase and cyclooxygenase activity in colon isolated from cancer patients].

PubMed

Franchi, A; Di Girolamo, G; de los Santos, A R; Marti, M L; Gimeno, M A

1998-01-01

The non-steroidal anti-inflammatory drugs (NSAIDS) induced ulcerations in the gastrointestinal tract are possibly associated with the reduction in prostaglandin (PGs) synthesis due to the inhibition of cyclooxygenase. On the other hand, it has been shown that 5-lipooxygenase products (5-LO) are ulcerogenic agents. In some cases, the utilization of NSAIDS stimulates 5-LO pathway to an excess of arachidonic acid because of cyclooxygenase inhibition. In these cases, the damage produced by NSAIDS is greater, since not only the cytoprotective PGs decrease but also the products of 5-LO are increased. The object of the present paper was to study the effects of lysine clonixinate (LC) and indomethacin (INDO) on PGs and 5-HETE synthesis. The concentrations used of LC (4 and 6 micrograms/ml) and INDO (0.035 micrograms/ml and 0.35 micrograms/ml) correspond to the plasmatic values reached with oral therapeutic doses for both drugs. The results show that in no case did LC reduce the production of PGE2. On the contrary INDO inhibited significantly the synthesis of PGe2. It is interesting to mention that LC 4 and 6 micrograms/ml inhibited drastically the production of 5-HETE. Only with the higher concentration of INDO did we observe a similar effect. These results may indicate an inhibitory action on 5-LO, the first enzyme in the metabolic pathway of arachidonic acid in the production of HETEs and LTS. We conclude that LC in therapeutic doses has a mechanism of action different from the classical NSAIDS. The data obtained in this study could explain the low incidence in gastrointestinal lesions with LC.

Evaluation of modified dichloran 18% glycerol (DG18) agar for enumerating fungi in wheat flour: a collaborative study.

PubMed

Beuchat, L R; Hwang, C A

1996-04-01

Dichloran 18% glycerol agar base supplemented with 100 micrograms of chloramphenicol ml-1 (DG18 agar) was compared to DG18 agar supplemented with 100 micrograms of Triton X-301 ml-1 (DG18T) and DG18 agar supplemented with 1 microgram of iprodione [3-(3,5-dichlorophenyl)-N-(1-methyl-ethyl)-2,4-dioxo-1-imidazolidine- carboxamide] ml-1 (DG18I agar) for enumeration of fungi in ten brands of wheat flour. As the flours contained low fungal populations, all were inoculated with two to four strains of xerophilic fungi (Aspergillus candidus, A. penicillioides, Eurotium amstelodami, E. intermedium, E. repens, E. rubrum, E. tonophilum, E. umbrosum and Wallemia sebi), after which counts ranged from 3.87 to 6.37 log10 CFU g-1. Significantly higher populations (p < 0.05) were detected in four flours: three were on DG18T compared to DG18 and DG18I agar. A. candidus had been inoculated into all three flours. E. amstelodami, E. intermedium, E. repens or E. tonophilum had also been inoculated into at least one of the three flours showing significantly higher numbers of CFU on DG18T agar. Analysis of collapsed data from all samples showed that DG18T agar was significantly better than DG18 or DG18I agars at p < 0.10 but not at p < 0.05. Coefficients of variation for reproducibility (among-laboratory variation) were 8.4%, 7.5% and 8.6%, respectively, for DG18, DG18T and DG18I agars. DG18I agar restricted colony development most, especially for Eurotium species. Naturally occurring Penicillium species grew equally well on DG18 and DG18T agars, whereas W. sebi grew well on all three media. DG18T agar was judged to be superior to DG18 and DG18I agars for enumerating fungi in wheat flours.

Bacteriostatic action of streptomycin on ribosomally resistant mutants (rpsL) of Salmonella typhimurium.

PubMed Central

Fernández, R O; Antón, D N

1987-01-01

Incubation of streptomycin-resistant (rpsL) mutants of Salmonella typhimurium in alkaline nutrient medium containing streptomycin brought about an inhibition of cell growth that was readily reversed by removing the antibiotic or neutralizing the medium. Growth inhibition was maximal at pH 8.2 and a streptomycin concentration of 800 micrograms/ml. A similar amount of dihydrostreptomycin had a negligible effect, and 10-times-higher concentrations of this antibiotic were required to reproduce the streptomycin action. Addition of streptomycin (400 micrograms/ml) to rpsL cells in alkaline (pH 8.2) nutrient medium caused inhibition of protein and DNA synthesis and also, but to a lower degree, of RNA synthesis. This effect on macromolecular synthesis was not due to ATP deprivation, since ATP content rose after addition of the antibiotic. At pH 8.2, the rate of entrance of streptomycin increased fourfold with respect to the rate at pH 7.0, leading to a large accumulation of streptomycin into rpsL cells. Uptake of the antibiotic was halted by addition of KCN or chloramphenicol. Equal uptake was obtained with 800 micrograms of dihydrostreptomycin or 400 micrograms of streptomycin per ml, yet the former did not affect cell growth at that concentration. It is concluded that high pH stimulates streptomycin and dihydrostreptomycin uptake by rpsL strains but only streptomycin accumulation causes growth inhibition in cells lacking the high-affinity ribosomal site. PMID:2449121

Selective effect of 2',6'-dihydroxy-4'-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis.

PubMed

Torres-Santos, E C; Moreira, D L; Kaplan, M A; Meirelles, M N; Rossi-Bergmann, B

1999-05-01

2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 micrograms/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 micrograms/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 micrograms of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

In vitro activity of AT-4140 against clinical bacterial isolates.

PubMed

Kojima, T; Inoue, M; Mitsuhashi, S

1989-11-01

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.

8-hydroxyquinoline inhibition of DNA synthesis and intragenic recombination during yeast meiosis.

PubMed

Mills, D

1978-06-14

Complete inhibition of sporulation was observed in two strains of Saccharomyces cerevisiae to which 8-hydroxyquinoline was added at a final concentration of 5 microgram/ml during the initial 4 to 6 h of sporulation. The cells were most sensitive to the inhibitor during 4 to 6 interval beginning at approximately 2 h (T2). Its addition during that interval resulted in 70 to 80% lethality in strain 4579 and about 40% in API at T24. When present from T0 onward, 5 microgram/ml of 8-hydroxyquinoline severely inhibited premeiotic DNA replication and reduced the frequency of intragenic recombination at the ade 2 and leu 2 loci by 70 and 100%, respectively, relative to control cultures which did not have the inhibitor present. During the period when the cells were most sensitive, the incorporation of 14C-leucine into protein and 14C-adenine into RNA was not inhibited nor was the polysome content affected. At 150 microgram/ml of inhibitor, incorporation of labeled precursors into RNA and protein were inhibited and the percentage of active ribosomes was reduced by 35% within 45 min, but neither transcription or translation appeared to be completely inhibited at this concentration of the inhibitor.

Development and use of a selective medium for isolation of Leuconostoc spp. from vegetables and dairy products.

PubMed Central

Benkerroum, N; Misbah, M; Sandine, W E; Elaraki, A T

1993-01-01

A selective medium (LUSM medium) for the isolation of Leuconostoc spp. was developed. This medium contained 1.0% glucose, 1.0% Bacto Peptone (Difco), 0.5% yeast extract (BBL), 0.5% meat extract (Difco), 0.25% gelatin (Difco), 0.5% calcium lactate, 0.05% sorbic acid, 75 ppm of sodium azide (Sigma), 0.25% sodium acetate, 0.1% (vol/vol) Tween 80, 15% tomato juice, 30 micrograms of vancomycin (Sigma) per ml, 0.20 microgram of tetracycline (Serva) per ml, 0.5 mg of cysteine hydrochloride per ml, and 1.5% agar (Difco). LUSM medium was used successfully for isolation and enumeration of Leuconostoc spp. in dairy products and vegetables. Of 116 colony isolates obtained from fresh raw milk, curdled milk, or various vegetables, 115 were identified as members of the genus Leuconostoc. A total of 89 of these isolates were identified to species; 13.5% of the isolates were Leuconostoc cremoris, 7.9% were Leuconostoc mesenteroides subsp. mesenteroides, 11.2% were Leuconostoc mesenteroides subsp. dextranicum, 16.9% were Leuconostoc mesenteroides subsp. paramesenteroides, 10.1% were leuconostoc lactis, and 40.4% were Leuconostoc oenos. When we compared the counts obtained for two Leuconostoc strains, Leuconostoc dextranicum 181 and L. cremoris JLL8, on MRS agar and LUSM medium, we found no significant difference between the values obtained on the two media. PMID:8434926

Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy.

PubMed

Albrecht, C F; Theron, E J; Kruger, P B

1995-09-01

Hypoxoside is the major diglucoside isolated from the corms of the plant family Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit with two distal catechol groups to which the glucose moieties are attached. It is non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in order to destroy endogenous beta-glucosidase activity. The latter catalyses hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10 micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect of rooperol manifested as vacuolisation of the cytoplasm and formation of pores in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic studies on mice dosed intragastrically with hypoxoside showed that it was deconjugated by bacterial beta-glucosidase to form rooperol in the colon. Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase II biotransformation products (sulphates and glucuronides) were present in the portal blood and bile. In contrast, however, in human serum after oral ingestion of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol metabolites isolated from human urine were non-toxic for BL6 melanoma cells in culture up to a concentration of 200 micrograms/ml. In the presence of beta-glucuronidase, which released rooperol from the metabolites, 50% growth inhibition was achieved at a 75 micrograms/ml metabolite concentration. The supernatant of a human melanoma homogenate could also cause deconjugation of the metabolites to form rooperol.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase.

PubMed

Dix, C J; Habberfield, A D; Cooke, B A

1984-06-15

The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2h. Forskolin also potentiated the action of LH on cyclic AMP production, but was only additive with cholera toxin. Preincubation of rat Leydig tumour cells with LH (1.0 micrograms/ml) for 1 h produced a desensitization of the subsequent LH (1.0 micrograms/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0 micrograms/ml), forskolin (100 microM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin or dibutyryl cyclic AMP was similar to the rate of heterologous desensitization induced by LH. These results demonstrate that in purified rat Leydig tumour cells LH produces an initial homologous desensitization of adenylate cyclase that involves a cyclic AMP-independent lesion at or proximal to the guanine nucleotide regulatory protein (G-protein). This is followed by heterologous desensitization, which can also be induced by forskolin or dibutyryl cyclic AMP, thus indicating that LH-induced heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase involves a cyclic AMP-dependent lesion that is after the G-protein.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

PubMed

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng ml-1. The unbound fraction of fentanyl in the plasma ranged from 17.8 to 44.4%, with a median value of 33.6%. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P < 0.05 in each case). Even with standardization for dosage, there was an eightfold variation in total plasma concentrations and 3.5-fold variation in unbound plasma concentrations of fentanyl. 3. There is considerable inter-patient variability in the pharmacokinetics of fentanyl with s.c. infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions.

PubMed Central

Firsov, A A; Mattie, H

1997-01-01

In comparative studies of different modes of administration (MAs) simulated in in vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an experimental design can provide a prediction of the antimicrobial effect (AME) of a given combination of drug, clinical isolate, and infection site, but may be inappropriate for accurate comparison of MAs. An alternative design providing comparison of different MAs with various antibiotic doses in a wide range and with evaluation of the respective relationships between AME and the AUC was proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e., monoexponentially decreasing concentrations (bolus doses) and constant concentrations (6-h continuous infusion), were in vitro simulated. The simulated initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0 micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was determined at each time (t) point as a difference (E) between the logarithms of viable counts (N) in the control cultures without antibiotic (NC) and in cultures exposed to antibiotics (NA). Time courses of E observed at different Co of Css levels were compared in terms of the areas under the E-t curves (ABBCt). The finite values of the ABBCt observed by the end of the 6 -h observation period, which are equivalent to the area between bacterial count-time curves observed in the absence and presence of antibiotic (ABBC), were plotted versus the respective AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at relatively low AUCs was inherent in both of the MAs. The superiority of bolus dosing over the infusions could be documented only for meropenem concentrations below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4 micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could practically be superimposed. On the whole, both MAs appeared to be equiefficient in terms of the ABBC. These results suggest that AUC analysis of the AME may be a useful tool for comparing different MAs. Such comparative studies should be designed in a manner that provides the use of similar AUC ranges, since the AUC may be considered as a common pharmacokinetic denominator in comparing one MA or dosing regimen to another. PMID:9021191

Effect of atropine and somatostatin on bombesin-stimulated plasma immunoreactive trypsin release in man.

PubMed

de Jong, A J; Klamer, M; Lamers, C B

1987-01-01

This study was undertaken to determine the effect of atropine and somatostatin, two inhibitors of intraduodenal pancreatic enzyme secretion, on bombesin-stimulated release of plasma immunoreactive trypsin in 6 healthy volunteers. Infusion of 5 ng/kg.min bombesin during 30 min induced significant increases in plasma trypsin from 206 +/- 20 to 334 +/- 44 ng/ml (p less than 0.01). Atropine (15 ng/kg as i.v. bolus followed by 5 ng/kg.h) had no influence on the bombesin-stimulated increase in plasma immunoreactive trypsin (207 +/- 20 to 326 +/- 54 ng/ml). Somatostatin (125 micrograms as i.v. bolus followed by 125 micrograms/h) also failed to inhibit the plasma trypsin response to bombesin (207 +/- 18 to 663 +/- 166 ng/ml). These results point to major differences in the regulation of plasma and intraduodenal trypsin secretion.

Enhanced interleukin-8 production in THP-1 human monocytic cells by lipopolysaccharide from oral microorganisms and granulocyte-macrophage colony-stimulating factor.

PubMed

Baqui, A A; Meiller, T F; Falkler, W A

1999-10-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-8 (IL-8) plays an important role in macrophage mediated inflammatory processes including exacerbation of periodontal diseases, one of the most common complications in GM-CSF receiving cancer patients. The effect of GM-CSF supplementation on IL-8 production was investigated in a human monocyte cell line THP-1, stimulated with lipopolysaccharide extracted from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. Resting THP-1 cells were treated with lipopolysaccharide (1 microgram/ml) of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) for varying time periods. The production of IL-8 in THP-1 cells was measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). A very low level of the cytokine IL-8 was produced constitutive in THP-1 cells. Starting from 8 h of treatment and afterwards GM-CSF alone significantly increased IL-8 production in THP-1 cells. Lipopolysaccharide (1 microgram/ml) extracts from either F. nucleatum or P. gingivalis amplified IL-8 production 500-800 times in comparison to resting THP-1 cells. When lipopolysaccharide of F. nucleatum or P. gingivalis was supplemented with 50 IU/ml of GM-CSF, there was a statistically significant enhanced production of IL-8 by THP-1 cells after 1 day to 7 days of treatment as compared with lipopolysaccharide treatment alone. GM-CSF (50 IU/ml) also significantly increased IL-8 production from 2-7 days of treatment of THP-1 cells when supplemented with a positive control, phorbol-12-myristate-13 acetate (PMA), as compared to PMA treatment alone. These investigations using the in vitro THP-1 human monocyte cell model indicate that there may be an increase in the response on a cellular level to oral endotoxin following GM-CSF therapy as evidenced by enhanced production of the tissue-reactive inflammatory cytokine, IL-8.

Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb.

PubMed Central

Brown, M J; Olver, R E; Ramsden, C A; Strang, L B; Walters, D V

1983-01-01

In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0.5 microgram/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption. Stimulus-response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0.1 and 1.0 microgram/min (0.55-5.5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion [( Ai]) and this was found to decrease from 0.43 ng/ml. (2.35 nM) at 132-4 days' gestation to 0.029 ng/ml. (0.16 nM) at gestations above 140 days. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50-150 min. The mean concentration of adrenaline in plasma increased from 0.087 ng/ml. (0.48 nM) in early labour to 6.86 ng/ml. (37.5 nM) in the last 50 min and to 7.17 ng/ml. (39.2 nM) in the early post-natal period. Mean noradrenaline levels at the same times were 1.71 ng/ml. (10.1 nM), 12.14 ng/ml. (71.8 nM) and 9.10 ng/ml. (53.9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non-labouring fetus of comparable gestational age. The upper airway of the fetus was shown to be capable of acting as a one-way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5-20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided. PMID:6655575

Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.).

PubMed

Cheng, Kun; Gao, Hua; Wang, Rong-Rong; Liu, Yang; Hou, Yu-Xue; Liu, Xiao-Hong; Liu, Kun; Wang, Wei

2017-02-21

The objective of this research is to implement extraction and degradation methods for the obtainment of 3- O -[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters-such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time-were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction time of 10 min at 70 °C under irradiation power 400W provided optimal extraction conditions. Compared with the conventional extraction techniques, including heat reflux extraction (HRE), Soxhlet extraction (SE), and ultrasonic extraction (UE), MAE produced higher extraction efficiency under a lower extraction time. DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4 H -pyran-4-one) saponin can be degraded to structurally stable saponin B by the loss of its DDMP group. The influence of pH and the concentration of potassium hydroxide on transformation efficiency of the target compound was investigated. A solution of 0.25 M potassium hydroxide in 75% aqueous ethanol was suitable for converting the corresponding DDMP saponins of chickpeasaponin B1. The implementation by the combining MAE technique and alkaline hydrolysis method for preparing chickpeasaponin B1 provides a convenient technology for future applications.

In vivo interaction of ketoconazole and sucralfate in healthy volunteers.

PubMed Central

Carver, P L; Berardi, R R; Knapp, M J; Rider, J M; Kauffman, C A; Bradley, S F; Atassi, M

1994-01-01

Absorption of ketoconazole is impaired in subjects with an increased gastric pH due to administration of antacids, H2-receptor antagonists, proton pump inhibitors, or the presence of hypochlorhydria. Sucralfate could provide an attractive alternative in patients receiving ketoconazole who require therapy for acid-peptic disorders. Twelve healthy human volunteers were administered a single 400-mg oral dose of ketoconazole in each of three randomized treatment phases. In phase A, ketoconazole was administered orally with 240 ml of water. In phase B, ketoconazole and sucralfate (1.0 g) were administered simultaneously with 240 ml of water. In phase C, ketoconazole was administered with 240 ml of water 2 h after administration of sucralfate (1.0 g) orally with 240 ml of water. A 680-mg oral dose of glutamic acid hydrochloride was administered 10 min prior to and with each dose of ketoconazole, sucralfate, or ketoconazole plus sucralfate. Simultaneous administration of ketoconazole and sucralfate led to a significant reduction in the area under the concentration-time curve and maximal concentration of ketoconazole in serum (78.12 +/- 12.20 versus 59.32 +/- 13.61 micrograms.h/ml and 12.34 +/- 3.07 versus 8.92 +/- 2.57 micrograms/ml, respectively; P < 0.05). When ketoconazole was administered 2 h after sucralfate, the observed ketoconazole area under the concentration-time curve was not significantly decreased compared with that of ketoconazole alone. The time to maximal concentrations in serum and the ketoconazole elimination rate constant were not significantly different in any of the three treatment phases. In patients receiving concurrent administration of ketoconazole and sucralfate, doses should be separated by at least 2 h. PMID:7910724

Killing of Saccharomyces cerevisiae by the lysosomotropic detergent N-dodecylimidazole.

PubMed Central

Hussain, M; Leibowitz, M J; Lenard, J

1987-01-01

The lysosomotropic detergent N-dodecylimidazole (C12-Im) has previously been found to kill mammalian cells by concentrating in lysosomes, followed by lysosomal disruption and release of cytotoxic enzymes into the cytoplasm. The action of C12-Im on Saccharomyces cerevisiae is described in this report. C12-Im prevented growth of colonies when present in 1% yeast extract-2% Bacto-Peptone-2% glucose plates at concentrations of 5 micrograms/ml or above, or when present in a soft agar overlay at 20 micrograms/ml. Treatment of cells suspended in glucose-containing buffer (pH 8.0, 37 degrees C) with C12-Im (6 micrograms/ml) caused greater than 95% cell death within 6 min. Dependence of killing on C12-Im concentration was sigmoidal, suggesting a cooperative mode of action. Killing was pH dependent, being much more effective at pH 8.0 than at pH 5.0. Ammonium sulfate and imidazole protected against killing if added before, but not after, the addition of C12-Im. Sensitivity to C12-Im was strongly growth dependent: the cells were most sensitive at early to mid-logarithmic phase of growth and became progressively less sensitive during progression through late logarithmic and stationary phase. Vacuolar disruption by C12-Im was demonstrated by using cells loaded with lucifer yellow CH or fluoresceinated dextran in their vacuoles; vacuoles of logarithmically growing cells were more sensitive than those of stationary-phase cells. These results suggest that vacuolar disruption by C12-Im may underlie its cytotoxic effects. Images PMID:3300529

Efficacy of imipenem/cilastatin in endocarditis.

PubMed

Dickinson, G; Rodriguez, K; Arcey, S; Alea, A; Greenman, R

1985-06-07

Imipenem, a potent new beta-lactam antibiotic, which is bactericidal against most pathogenic bacteria, and cilastatin, a dehydropeptidase inhibitor combined with imipenem to prevent the metabolism of imipenem in the kidney, were evaluated in the treatment of bacterial endocarditis. Seventeen patients, including 14 who used intravenous drugs, were treated with imipenem/cilastatin in a dose of 500 mg each infused over 30 minutes every six hours. The mean duration of treatment was 29 days with a range of 21 to 56 days. Causative bacteria were Staphylococcus aureus in 10 patients, S. aureus plus group B Streptococcus in one, viridans group Streptococcus in two, Neisseria subflava, Eikenella corrodens, and group G Streptococcus in one patient, and Staphylococcus epidermidis, Hemophilus aphrophilus, and Enterobacter aerogenes in one patient each. The minimal bactericidal concentration of imipenem against 16 of 18 isolates tested was 0.04 micrograms/ml, 1 microgram/ml against H. aphrophilus, and 0.4 micrograms/ml against E. aerogenes. The site of infection was the right side of the heart in 11 patients, the left side in five, and both sides in one. The mean number of days to defervescence was 9.7. All patients were cured, and none required cardiac surgery. Adverse effects were few and interrupted treatment occurred in only one patient who had acute dyspnea during an infusion on Day 26 of therapy. Imipenem/cilastatin appears to be a relatively safe and highly effective treatment of staphylococcal endocarditis in intravenous drug users; too few patients with endocarditis caused by other bacteria were treated to allow a firm statement about efficacy in non-staphylococcal endocarditis.

[Inhibition rate of gamma-aminolevulinic acid dehydratase activity in erythrocytes as a reliable index for individual workers of low lead exposure].

PubMed

Hirano, H; Omichi, M; Ohishi, H; Ishikawa, K; Hirashima, N

1983-09-01

As the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes is decreased by lead exposure, we considered that a net reduction of ALAD activity by lead in blood should be the difference between the activity fully activated with zinc (Zn2+) and dithiothreitol (DTT) and that without activation. The optimal condition of activation of ALAD was found by addition of 0.25 mM of Zn2+ and 10 mM of DTT in the reaction mixture. Judging from our previous results that the amount of inhibition of ALAD activity can be represented as the rate of inhibition and is closely correlated with the dose of lead administered to rabbits, the inhibition rate of ALAD activity and lead content in blood (Pb-B) of lead workers were measured. The scatter diagram obtained from the inhibition rate and lead content in blood has two groups being divided at 50 micrograms/ml of Pb-B. In one group less than 50 micrograms/100 ml of Pb-B, the inhibition rate has been closely related to Pb-B., the regression equation being Y = 1.82 X + 11.7, and the correlation coefficient + 0.926. In another group more than 50 micrograms/100 ml of Pb-B the inhibition rate remained constant at the 90% level. Measurement of the inhibition rate suggests to have practical validity for monitoring lead exposure in workers, and by means of a nomograph lead content in blood can be estimated from the inhibition rate.

Indoor mite allergens in patients with respiratory allergy living in Porto, Portugal.

PubMed

Plácido, J L; Cuesta, C; Delgado, L; da Silva, J P; Miranda, M; Ventas, P; Vaz, M

1996-09-01

We investigated the levels of mite allergens (Der p 1, Der f 1, Der 2, and Lep d 1) in dust samples from the homes of 59 patients with asthma, 36 sensitized to house-dust mites (HDM) and 23 to grass pollen (controls), living in Porto, northern Portugal. The relationship between exposure and sensitization to HDM and the influence of housing conditions on mite-allergen levels were also evaluated. Der p 1 (median 9.2 micrograms/g) and Der 2 (4.6 micrograms/g) were the main allergens, while Der f 1 and Lep d 1 levels were always < 1 microgram/g dust and undetectable in 11% and 47% of samples, respectively. All HDM-sensitized asthmatics were exposed to Der p 1 levels > 2 micrograms/g and their homes contained significantly higher levels of Der p 1 (median 12.5 vs 6.4 micrograms/g; P = 0.008) and Der 2 (6.2 vs 3.0 micrograms/g; P = 0.004) when compared to the control group. A significant correlation was observed between the exposure to Der p 1 and the wheal area at skin testing with the Dermatophagoides pteronyssinus (Dp) extract (P = 0.01) as well as with serum specific IgE levels to Dp (P = 0.03). Patients with higher levels of serum specific IgE (> or = 17.5 HRU/ml) were also more frequently exposed to Der p 1 levels > or = 10 micrograms/g (P = 0.002). Old homes, presence of carpets, and signs of dampness were conditions associated with significantly higher levels of mite allergens. In conclusion, we found high levels of Der p 1 and Der 2 particularly in the homes of HDM-sensitized patients and we confirm the relationship between exposure and sensitization to HDM, assessed by both in vivo and in vitro methods. In additional to a favorable outdoor climate, we found in our region housing conditions propitious to mite growth, suggesting that specific geographic characteristics must also be taken into account for the correct planning of mite-avoidance measures.

The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo.

PubMed

Cheung, D; Bel, E H; Den Hartigh, J; Dijkman, J H; Sterk, P J

1992-06-01

Neuropeptides such as neurokinin A (NKA) have been proposed as important mediators of bronchoconstriction and airway hyperresponsiveness in asthma. Inhaled NKA causes bronchoconstriction in patients with asthma, but not in normal subjects. This is possibly due to the activity of an endogenous neuropeptide-degrading enzyme: neutral endopeptidase (NEP). We investigated whether a NEP-inhibitor, thiorphan, reveals bronchoconstriction to NKA or NKA-induced changes in airway responsiveness to methacholine in normal humans in vivo. Eight normal male subjects participated in a double-blind crossover study, using thiorphan as pretreatment to NKA challenge. Dose-response curves to inhaled NKA (8 to 1,000 micrograms/ml, 0.5 ml/dose) were recorded on 2 randomized days 1 wk apart, and methacholine tests were performed 48 h before and 24 h after the NKA challenge. Ten minutes prior to NKA challenge the subjects inhaled either thiorphan (2.5 mg/ml, 0.5 ml) or placebo. To detect a possible nonspecific effect of thiorphan, we investigated the effect of the same pretreatment with thiorphan or placebo on the dose-response curve to methacholine in a separate set of experiments. The response was measured by the flow from standardized partial expiratory flow-volume curves (V40p), expressed in percent fall from baseline. NKA log dose-response curves were analyzed using the area under the curve (AUC) and the response to the highest dose of 1,000 micrograms/ml (V40p,1000). The methacholine dose-response curves were characterized by their position (PC40V40p) and the maximal-response plateau (MV40p). Baseline V40p was not affected by either pretreatment (p greater than 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic products of microorganisms. 170. On the antibiotic activity of cladosporin.

PubMed

Anke, H; Zähner, H

1978-03-01

Cladosporin was isolated from the cultures of three species of the genus Eurotium. Cladosporin inhibited the growth of several fungi and at very low concentrations the growth of Bacillus brevis and Clostridium pasteurianum. Bacillus subtilis and most other Gram-positive bacteria were not sensitive. Gram-negative bacteria and yeasts were not affected by concentrations up to 100 microgram/ml. Dimethyl cladosporin showed only week activity against Bacillus brevis with the minimal inhibitory concentrations being a 100 times higher than of cladosporin. The incorporation of leucine and uracil into acid insoluble material in Bacillus brevis cells was completely inhibited by concentration of 0.5 microgram/ml cladosporin. The incorporation of thymidine was not affected at this concentration.

Stability of thiopental and pentobarbital in human plasma determined with a new easy and specific gas chromatography-mass spectrometry assay.

PubMed

Martens-Lobenhoffer, J

1999-08-01

A gas chromatographic-mass spectrometric (GC-MS) assay for the determination of thiopental and its main metabolite pentobarbital in human plasma is presented in this study. The sample preparation consists only in the addition of the internal standard barbital and an acidic extraction with ethyl acetate. Analytical separation is accomplished on a RTX-1 15 m x 0.25 mm capillary column with a film thickness of 0.5 micron. The effluent is observed by a mass selective detector operating in the single ion monitoring mode. The limits of detection are 5 ng/ml for pentobarbital and 10 ng/ml for thiopental, the intra-day variabilities are 2.2% and 4.0% and the inter-day variabilities are 3.3% and 7.1% at concentrations of 5 micrograms/ml, respectively. Applying this assay, the stability of thiopental and pentobarbital in human plasma was tested at concentrations of 5 micrograms/ml each. Thiopental is stable in human plasma at least over 41 days stored at -20 degrees C and 5 degrees C, respectively. A decay of about 2%/day is observed under storage at ambient temperature (19-20 degrees C). Pentobarbital is stable under all storage conditions. Methanolic solutions of thiopental are stable for 83 days under storage at 5 degrees C. Aqueous solutions of thiopental-sodium are stable for at least 23 days under storage at 5 degrees C or ambient temperature.

Stability of amoxicillin-clavulanate in BACTEC medium determined by high-performance liquid chromatography and bioassay.

PubMed Central

Moore, T D; Horton, R; Utrup, L J; Miller, L A; Poupard, J A

1996-01-01

The stabilities of amoxicillin (16 micrograms/ml) and clavulanate (8 micrograms/ml), alone and in combination in BACTEC medium (Middlebrook 7H12B medium), were determined by high-performance liquid chromatography (HPLC) and bioassay. By HPLC, the half-life of amoxicillin (trihydrate and sodium) in combination with clavulanate in nonradiolabelled 7H12B medium was 6.7 days, whereas the half-life of clavulanate in combination with amoxicillin was 2.0 days. By bioassay, the half-lives of amoxicillin trihydrate and clavulanate in radiolabelled 7H12B medium were comparable (7 and 2 days, respectively) to those determined by HPLC. When clavulanate was tested alone, the half-life was determined to be 1.88 days by HPLC and 1.87 days by bioassay. The relatively short half-life of clavulanate can be adjusted by a procedure of "topping up," or adding one-half the concentration of clavulanate every second day, in order to allow accurate amoxicillin-clavulanate MIC testing with the BACTEC mycobacterial susceptibility system. PMID:8727931

Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients.

PubMed Central

Schaad, U B; Casey, P A; Cooper, D L

1983-01-01

Pharmacokinetics of a parenteral formulation comprised of 5 parts of amoxicillin and 1 part of clavulanic acid were determined in 12 pediatric patients, 2 to 14 years of age. A single dose amounting to 25 mg of amoxicillin and 5 mg of clavulanic acid per kg of body weight was infused intravenously over 2 min. Mean plasma concentrations 5 min after dosing were 89.4 micrograms of amoxicillin per ml and 19.5 micrograms of clavulanic acid per ml. Terminal phase plasma half-lives were 1.2 and 0.8 h, respectively. The data acquired in this study indicate that amoxicillin and clavulanic acid are pharmacokinetically compatible. Moreover, taken with assessment of microbiological activities by others, the present data suggest that intravenous administration of 25 mg of amoxicillin plus 5 mg of clavulanic acid per kg every 6 h is a reasonable starting regimen for assessing the activity of the combined drug formulation in noninvasive childhood diseases caused by Haemophilus influenzae, Staphylococcus aureus, Streptococci spp., Neisseria spp., Branhamella catarrhalis, and other susceptible organisms. Images PMID:6838187

Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients.

PubMed

Schaad, U B; Casey, P A; Cooper, D L

1983-02-01

Pharmacokinetics of a parenteral formulation comprised of 5 parts of amoxicillin and 1 part of clavulanic acid were determined in 12 pediatric patients, 2 to 14 years of age. A single dose amounting to 25 mg of amoxicillin and 5 mg of clavulanic acid per kg of body weight was infused intravenously over 2 min. Mean plasma concentrations 5 min after dosing were 89.4 micrograms of amoxicillin per ml and 19.5 micrograms of clavulanic acid per ml. Terminal phase plasma half-lives were 1.2 and 0.8 h, respectively. The data acquired in this study indicate that amoxicillin and clavulanic acid are pharmacokinetically compatible. Moreover, taken with assessment of microbiological activities by others, the present data suggest that intravenous administration of 25 mg of amoxicillin plus 5 mg of clavulanic acid per kg every 6 h is a reasonable starting regimen for assessing the activity of the combined drug formulation in noninvasive childhood diseases caused by Haemophilus influenzae, Staphylococcus aureus, Streptococci spp., Neisseria spp., Branhamella catarrhalis, and other susceptible organisms.

Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219).

PubMed Central

Wise, R; Mortiboy, D; Child, J; Andrews, J M

1996-01-01

A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens. PMID:8787877

[Economical benefit of continuous total intravenous anesthesia].

PubMed

Onaka, M; Yamamoto, H; Akatsuka, M; Mori, H

1999-05-01

Total intravenous anesthesia (TIVA) has been recommended in view of avoiding air pollution. However, intermittent administration of anesthetic agents has a large disadvantage of delayed emergence. We reported that continuous TIVA with propofol, ketamine, vecuronium and buprenorphine (PKBp) could bring rapid emergence. In this study, we calculated and compared the cost of anesthesia in the subjects who had undergone general anesthesia either with continuous PKBp or nitrous oxide-oxygen-sevoflurane. In group PKBp subjects, after induction with propofol, ketamine, vecuronium and buprenorphine, anesthesia was maintained with continuous intravenous administration of propofol corresponding to the patient's age using twice step down method; ketamine (240 micrograms.kg-1.h-1), vecuronium (80 micrograms.kg-1.h-1) and buprenorphine (0.4 microgram.kg-1.h-1). Group GOS subjects, after the same induction method, received nitrous oxide, sevoflurane and vecuronium. Moreover, the group GOS subjects were divided to two groups; the high flow GOS (N2O:O2:sevoflurane = 4 l:2 l:30 ml) and the low flow GOS (N2O:O2:sevoflurane = 2 l:1 l:15 ml). Continuous PKBp group showed lower cost than the high flow GOS group. The PKBp group showed lower cost than the low flow GOS group except in patients weighing more than 100 kg. Furthermore, we calculated the cost of continuous PKBp anesthesia in Japan, U.S.A. and U.K. The U.S.A. cost of PKBp was higher than the Japanese and the U.K., because the cost of ketamine in U.S.A. is higher than in the other countries. Continuous PKBp is more economical than the high flow GOS, and continuous PKBp in Japan is more economical than in U.S.A.

Requirement of vitamin C for cartilage calcification in a differentiating chick limb-bud mesenchymal cell culture.

PubMed

Boskey, A L; Stiner, D; Doty, S B; Binderman, I

1991-01-01

Mesenchymal cells isolated from stage 21-24 chick limb-buds plated in a micro-mass culture differentiate to form chondrocytes and synthesize a calcifiable matrix. In the presence of inorganic phosphate (4 mM), hydroxyapatite mineral deposits around cartilage nodules. Ascorbic acid is, in general, an essential co-factor for extracellular matrix synthesis in culture, since it is required for collagen synthesis. In this study we demonstrate that in the absence of ascorbic acid supplementation in the mesenchymal cell cultures, mineral deposition (indicated by X-ray diffraction, measurement of Ca:hydroxyproline ratio, and 45Ca uptake) does not occur. Concentrations of 10-50 micrograms/ml ascorbate were compared to find the "optimal" concentration for cell mediated mineralization; 25 micrograms/ml was selected as optimal based on matrix appearance at the EM level and the rate of 45Ca uptake. High concentrations of ascorbic acid (greater than 75 micrograms/ml), while increasing the amount of hydroxyproline in the matrix synthesized, caused some cell death and hence less cell-mediated mineralization. This study demonstrates both the need for viable cells and a proper matrix for in vitro cell-mediated mineralization, and shows that varying the concentration of L-ascorbate (vitamin C) in the medium can have a marked effect on mineralization in vitro.

In vitro sensitivity of Hungarian Actinobaculum suis strains to selected antimicrobials.

PubMed

Biksi, I; Major, Andrea; Fodor, L; Szenci, O; Vetési, F

2003-01-01

In vitro antimicrobial sensitivity of 12 Hungarian isolates and the type strain ATCC 33144 of Actinobaculum suis to different antimicrobial compounds was determined both by the agar dilution and by the disc diffusion method. By agar dilution, MIC50 values in the range of 0.05-3.125 micrograms/ml were determined for penicillin, ampicillin, ceftiofur, doxycycline, tylosin, pleuromutilins, chloramphenicol, florfenicol, enrofloxacin and lincomycin. The MIC50 value of oxytetracycline and spectinomycin was 6.25 and 12.5 micrograms/ml, respectively. For ofloxacin, flumequine, neomycin, streptomycin, gentamicin, nalidixic acid, nitrofurantoin and sulphamethoxazole + trimethoprim MIC50 values were in the range of 25-100 micrograms/ml. With the disc diffusion method, all strains were sensitive to penicillin, cephalosporins examined, chloramphenicol and florfenicol, tetracyclines examined, pleuromutilins, lincomycin and tylosin. Variable sensitivity was observed for fluoroquinolones (flumequine, enrofloxacin, ofloxacin), most of the strains were susceptible to marbofloxacin. Almost all strains were resistant to aminoglycosides but most of them were sensitive to spectinomycin. A strong correlation was determined for disc diffusion and MIC results (Spearman's rho 0.789, p < 0001). MIC values of the type strain and MIC50 values of other tested strains did not differ significantly. Few strains showed a partially distinct resistance pattern for erythromycin, lincomycin and ampicillin in both methods.

Isolation and characterization of a nonpigmented variant of Porphyromonas endodontalis.

PubMed

Suzuki, K; Ikeda, T; Nakamura, H; Yoshimura, F

1997-06-01

Porphyromonas endodontalis forms dark colonies on media containing blood. We isolated, from an infected root canal, a non-black-pigmented P. endodontalis variant, KSEW01, which forms beige colonies on blood agar media. To characterize this variant, we compared its properties with those of two black-pigmented P. endodontalis strains, ATCC35406 and KSE105. Strain KSEW01 had a gelatinase activity comparable to that of the pigmented strains. Cell lysates of these three strains resolved by SDS-PAGE electrophoresis showed similar protein patterns. Quantitative DNA-DNA hybridization experiments indicated high homology between the nonpigmented strain KSEW01 and the two dark-pigmented strains. From these results, we identified strain KSEW01 as a P. endodontalis nonpigmented variant. DNA restriction endonuclease analysis indicated that the variant was closely related to a pigmented strain, KSE105. In contrast to the pigmented strains, strain KSEW01 did not degrade hemoglobin and formed no vesicles when cultured in the presence of blood. The susceptibilities of these three strains to 22 antibiotics were similar except for vancomycin. The nonpigmented variant was the most resistant to vancomycin (MIC: ATCC35406, 6.25 micrograms/ml; KSE105,12.5 micrograms/ml; KSEW01, 100 micrograms/ml). Overall, a relationship may exist between the presence of black-pigmentation and outer membrane systems of P. endodontalis.

[Blood lead levels in children from a ceramic center with respect to residence and parental occupation].

PubMed

Ferri, F; Candela, S; Bedeschi, E; Picciati, A M; Davoli, V; Rinaldi, L; Riccò, D

1998-01-01

In a survey carried out in 1981, Pb exposure of children living in two geographical areas of the district of Scandiano and attending the first year of primary school was studied. The two areas were different concerning both traffic and the presence of ceramic tile industries, thus suggesting a different exposure of children. The survey demonstrated blood lead levels (PbB) markedly higher than 10 micrograms/100 ml, a value recently identified by the Centers for Disease Control (CDC, Atlanta, USA) as the limit beyond which children's learning capacity may be damaged. It was evident that both the occupational exposure of parents and, to a lower extent, the residence in zones with higher levels of pollution influenced PbB levels. During the last ten years significant improvements have led to the reduction of atmospheric emissions and of occupational exposure of ceramic workers. A new survey has been carried out in 1995. We examined 147 children attending the first year of primary school, and living in two zones for which a different level of Pb exposure could be assumed. In both zones, a clear reduction of PbB was observed in comparison with data obtained in 1981. Mean and standard deviation for PbB in the two groups were 4.1 +/- 1.71 and 4.5 +/- 2.04 micrograms/100 ml, with median values of 3.7 and 4.0 micrograms/100 ml, respectively. Only two cases (1.4%) exceeded the limit values proposed by CDC. Although the mean PbB were much lower than those observed in 1981, higher PbB were found in children whose parents were occupationally exposed to Pb. Maternal exposure seems to be particularly important in determining PbB in children. In comparison with data from the international literature, our results are very close to those obtained for children living in Scandinavian countries, in Germany or in France and rather different from those obtained by other authors in Italy.

Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4.

PubMed Central

Musher, D M; Johnson, B; Watson, D A

1990-01-01

We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G. PMID:2254015

Treatment of fish parasites. 11. Morphogenesis of Henneguya laterocapsulata Landsberg, 1987 (Myxosporea, Myxozoa), and the effects of a new triazine derivative, HOE 092 V, on its developmental stages: a light and electron microscopy study.

PubMed

Schmahl, G; Obiekezie, A; Raether, W

1993-01-01

The ultrastructure of sporogenesis was studied in Henneguya laterocapsulata parasitizing the skin of hybrid catfish (Clarias gariepinus x Heterobranchus bidorsalis) in Nigeria. Sporogenesis started when a generative cell was surrounded by a second nondividing cell (i.e., envelope cell). By subsequent divisions of the generative cell, ten cells were produced, which finally became arranged into two spore-producing units. Each unit consisted of a binucleate sporoplasm, two capsulogenic cells, and two valvogenic cells. Apparently capsulogenesis, valvogenesis, and sporoplasm differentiation occurred concomitantly. In research for chemotherapy of fish parasitized by myxosporeans a new triazine derivative, 2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)-phenyl]-1-me thy l- hexahydro-1,2,4-triazine-3,5-dion (HOE 092 V), was tested in vivo against the uni- and multicellular developmental stages of H. laterocapsulata. Naturally infected catfish were incubated in water containing 0, 2.5, 5, and 10 micrograms HOE 092 V/ml or the pure solvent for 3 h. After the fish had been returned into fresh water, they were killed 1 day after the treatment and the plasmodia were studied by means of light and transmission electron microscopy. Starting with a dose of 2.5 micrograms HOE 092 V/ml, the pericyte's outer membrane was broken in the bi- and multicellular stages. The number of ribosomes in the bi- and multicellular stages decreased. In the multicellular stages the rough endoplasmic reticula of the capsulogenic cells were enlarged. Treatment with 5 micrograms HOE 092 V/ml led to breaks in the limiting outer membranes of the capsulogenic cells and to vacuolization of their peripheral cytoplasm. In early prespore stages a decrease in the number of spherical inclusions was recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. The Norwegian Yeast Study Group.

PubMed Central

Sandven, P; Bjørneklett, A; Maeland, A

1993-01-01

All Candida albicans isolates in Norwegian microbiological laboratories in 1991 judged clinically important (except vaginal isolates) were collected. The isolates were tested for susceptibility to fluconazole with an agar dilution test and a commercially available agar diffusion test. A total of 212 strains (95%) were susceptible to fluconazole, and MICs for most of the strains (92%) were < or = 1.56 micrograms/ml. The agar diffusion test using a 15-micrograms tablet and a 48-h incubation period separated resistant from susceptible strains with a wide margin. The only exception was a strain for which the MIC was 6.25 micrograms/ml. The difference in zone size between the resistant and the susceptible populations of strains was 11 mm. Accordingly, it appears that the agar diffusion test is an appropriate method for detecting fluconazole resistance. The 12 fluconazole-resistant isolates originated from eight AIDS patients with oral or esophageal Candida infections. Seven of the patients had been given fluconazole for 1 month or more, often as self medication. Four had infections that were clinically resistant to fluconazole; one additional patient responded only when the dose was increased. All isolates recovered from these patients were analyzed by multilocus enzyme electrophoresis. The 12 C. albicans isolates belonged to five electrophoretic types, but three of four patients attending one hospital had isolates belonging to one electrophoretic type. One possible explanation for this finding could be that a nosocomial spread of resistant strains has occurred. PMID:8285631

Antioxidant and wound healing potential of saponins extracted from the leaves of Algerian Urtica dioica L.

PubMed

Razika, Laoufi; Thanina, Affif Chaouche; Nadjiba, Chebouti-Meziou; Narimen, Benhabyles; Mahdi, Dahmani Mohamed; Karim, Arab

2017-05-01

The Nettle is a herbaceous and vivace plant of Asian origin. It is integrated in several areas especially alimentary, agricultural, industrial and medicinal. The aim of this work is to demonstrate through pharmacological tests a possible antioxidant and wound healing effect of crude saponins of the leaves of Urtica dioica L. The extraction method is based on the degree of solubility of saponins in organic solvents. The antioxidant activity of the leaves extracts was evaluated by the diphenyl-picryl-hydrazyl test (DPPH). The wound healing effect is interpreted on the basis of the healing time and the evaluation of the surface of wounds. It appears from this study that the Nettle is rich in saponins, either 4.08% to 30 g of plant powder. The results also showed significant antioxidant effect similar to that of ascorbic acid (p> 0.05) with an IC 50 of 0.159mg/ml. As regards the healing power, treatment of rats with the product based on crude saponins is achieved after 15 days, either 100% of wound reduction. This value is much higher than that obtained by the reference product (Madécassol®) on the same duration of treatment with 93.73% of wound reduction. The achievement of pharmacological tests has thus shown that crude saponins extracted from the leaves of Urtica dioica L. can be integrated into the pharmaceutical field or even in cosmetic.

Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

PubMed

Seabrook, G R; Main, M; Bowery, B; Wood, N; Hill, R G

1992-04-01

1. The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.6. It is evident that rat and guinea-pig superior cervical ganglia possess both NK, and NK3 receptors, but that their net contribution to depolarizations are different between the two species. The depolarizations in guinea-pig SCG are mediated predominantly by an NK3 subtype and in rat SCG by an NK, receptor subtype.

Lead and cadmium in human placentas and maternal and neonatal blood (in a heavily polluted area) measured by graphite furnace atomic absorption spectrometry.

PubMed Central

Baranowska, I

1995-01-01

OBJECTIVE--To measure the concentrations of the trace elements lead and cadmium in human placenta and in maternal and neonatal (cord) blood. To assess the influence of the strongly polluted environment on the content of metals in tissues and on the permeability of placenta to cadmium and lead. Various methods of mineralisation were tested before analysis. METHODS--Graphite furnace atomic absorption spectrometry was used for the determination of lead and cadmium. The samples for analysis were prepared by mineralisation under pressure in a Teflon bomb (HNO3, 110 degrees C), by wet ashing under normal pressure (HNO3 + H2O2 for 12 hours), and by microwave digestion in concentrated nitric acid. RESULTS--In analysed samples the following mean concentrations of cadmium and lead were found: in venous blood Pb = 72.50 ng/ml, Cd = 4.90 ng/ml; in placenta Pb = 0.50 microgram/g, Cd = 0.11 microgram/g; in cord blood Pb = 38.31 ng/ml, Cd = 1.13 ng/ml. CONCLUSION--High concentrations of lead and cadmium were found in placentas and in maternal blood whereas in neonatal blood there was an increased concentration of lead and only traces of cadmium. It is concluded that the placenta is a better barrier for cadmium than for lead. Among the examined methods of mineralisation, microwave digestion was the best. PMID:7795737

Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment.

PubMed

Kaiser, T N; Lojewski, A; Dougherty, C; Juergens, L; Sahar, E; Latt, S A

1982-03-01

DNA flow histogram analysis, using 33342 Hoechst as a stain, has been used to detect the effect of the potentially bifunctional alkylating agent, mitomycin C (MMC) on dermal fibroblasts from patients with Fanconi's anemia (FA), a hereditary human disease characterized by pancytopenia, hypersensitivity to DNA-crosslinking agents, congenital abnormalities and a predisposition for neoplasia. At 24 or 48 hr after a 2-hr exposure to 0.05 or 0.10 micrograms/ml MMC, (3)HdT incorporation was reduced to a greater extent in FA cells than in normal cells. Cells sorted from the last half of S phase showed a slightly greater inhibition of (3)HdT incorporation than did those sorted from the first half of S. Fanconi's anemia cells exhibited a marked accumulation in the G(2) + M peak of flow histograms following exposure to MMC. Twenty-four hr after treatment with .0.5 micrograms/ml MMC, the G(2) + M fraction of FA cells (eight lines) increased to more than 0.5 from a control value of approximately 0.02. Both normals (six lines) and heterozygotes (eight lines) showed, on the average, much less of a G(2) + M increment than did FA cells, even after exposure to 0.1 micrograms/ml MMC. Examination of cells sorted from the G(2) + M peak revealed that MMC-treated FA cells were blocked prior to mitosis. To determine whether the response of FA cells was specific for bifunctional alkylating agent, cells were also treated with ethylmethanesulfonate, a monofunctional agent. Twenty-four hours after exposure to 0.25 or 0.5 mg/ml ethylmethanesulfonate, FA and normal cells showed similar, small increases in the G(2) + M peak. The results suggest the utility of flow cytometry in the diagnostic evaluation of fibroblasts from patients suspected of having Fanconi's anemia.

Molecularly Characterized Solvent Extracts and Saponins from Polygonum hydropiper L. Show High Anti-Angiogenic, Anti-Tumor, Brine Shrimp, and Fibroblast NIH/3T3 Cell Line Cytotoxicity

PubMed Central

Ayaz, Muhammad; Junaid, Muhammad; Ullah, Farhat; Sadiq, Abdul; Subhan, Fazal; Khan, Mir Azam; Ahmad, Waqar; Ali, Gowhar; Imran, Muhammad; Ahmad, Sajjad

2016-01-01

Polygonum hydropiper is used as anti-cancer and anti-rheumatic agent in folk medicine. This study was designed to investigate the anti-angiogenic, anti-tumor, and cytotoxic potentials of different solvent extracts and isolated saponins. Samples were analyzed using GC, Gas Chromatography–Mass Spectrometry (GC–MS) to identify major and bioactive compounds. Quantitation of antiangiogenesis for the plant's samples including methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) were performed using the chick embryo chorioallantoic membrane (CAM) assay. Potato disc anti-tumor assay was performed on Agrobacterium tumefaciens containing tumor inducing plasmid. Cytotoxicity was performed against Artemia salina and mouse embryonic fibroblast NIH/3T3 cell line following contact toxicity and MTT cells viability assays, respectively. The GC–MS analysis of Ph.Cr, Ph.Hex, Ph.Chf, Ph.Bt, and Ph.EtAc identified 126, 124, 153, 131, and 164 compounds, respectively. In anti-angiogenic assay, Ph.Chf, Ph.Sp, Ph.EtAc, and Ph.Cr exhibited highest activity with IC50 of 28.65, 19.21, 88.75, and 461.53 μg/ml, respectively. In anti-tumor assay, Ph.Sp, Ph.Chf, Ph.EtAc, and Ph.Cr were most potent with IC50 of 18.39, 73.81, 217.19, and 342.53 μg/ml, respectively. In MTT cells viability assay, Ph.Chf, Ph.EtAc, Ph.Sp were most active causing 79.00, 72.50, and 71.50% cytotoxicity, respectively, at 1000 μg/ml with the LD50 of 140, 160, and 175 μg/ml, respectively. In overall study, Ph.Chf and Ph.Sp have shown overwhelming results which signifies their potentials as sources of therapeutic agents against cancer. PMID:27065865

Stimulation of gastrin release and gastric secretion: effect of bombesin and a nonapeptide in fistula dogs with and without fundic vagotomy.

PubMed

Hirschowitz, B I; Gibson, R G

1978-01-01

Bombesin and a synthetic bombesin nonapeptide were studied by intravenous infusion at a dose of 0.5 microgram.kg-1.h-1 for 4 h in 7 dogs with esophagostomy and gastric fistula. In 3 of the dogs who had highly selective (fundic) vagotomy, mean integrated gastrin output over 4 h was double that in the 4 dogs with vagi intact during both nonapeptide (1,554 vs. 700 pg.ml-1.4 h-1) and bombesin infusion (2,442 vs. 1,440 pg.ml-1.4 h-1). Peak concentrations of serum gastrin reached during bombesin (490 +/- 100 vs. 320 +/- 90) were higher than those during nonapeptide infusion (270 +/- 40 vs. 160 +/- 28 pg/ml) in the vagotomized and intact dogs, respectively. The difference between vagotomized and vagally intact dogs suggests that the fundic vagotomy removed an inhibitor of gastrin release from the innervated antrum. Despite these differences in gastrin release, gastric acid output with the two peptides was the same (49--52 mEq/4 h) whether the fundus was denervated or innervated. This suggests that bombesin may stimulate gastric acid secretion by the release of an additional secretagogue which is not measured by the gastrin assay. Neither of the two inhibitors of gastrin release--antral acidification to pH 1.4 or less or atropine (100 microgram/kg)-- inhibited gastrin release by bombesin, even though the atropine reduced acid output by 80%. Bombesin is a potent gastric stimulus whose action is only partly explained by the measured gastrin release.

Production of low-affinity penicillin-binding protein by low- and high-resistance groups of methicillin-resistant Staphylococcus aureus.

PubMed Central

Murakami, K; Nomura, K; Doi, M; Yoshida, T

1987-01-01

Methicillin- and cephem-resistant Staphylococcus aureus (137 strains) for which the cefazolin MICs are at least 25 micrograms/ml could be classified into low-resistance (83% of strains) and high-resistance (the remaining 17%) groups by the MIC of flomoxef (6315-S), a 1-oxacephalosporin. The MICs were less than 6.3 micrograms/ml and more than 12.5 micrograms/ml in the low- and high-resistance groups, respectively. All strains produced penicillin-binding protein 2' (PBP 2'), which has been associated with methicillin resistance and which has very low affinity for beta-lactam antibiotics. Production of PBP 2' was regulated differently in low- and high-resistance strains. With penicillinase-producing strains of the low-resistance group, cefazolin, cefamandole, and cefmetazole induced PBP 2' production about 5-fold, while flomoxef induced production 2.4-fold or less. In contrast, penicillinase-negative variants of low-resistance strains produced PBP 2' constitutively in large amounts and induction did not occur. With high-resistance strains, flomoxef induced PBP 2' to an extent similar to that of cefazolin in both penicillinase-producing and -negative strains, except for one strain in which the induction did not occur. The amount of PBP 2' induced by beta-lactam antibiotics in penicillinase-producing strains of the low-resistance group correlated well with resistance to each antibiotic. Large amounts of PBP 2' in penicillinase-negative variants of the low-resistance group did not raise the MICs of beta-lactam compounds, although these strains were more resistant when challenged with flomoxef for 2 h. Different regulation of PBP 2' production was demonstrated in the high- and low-resistance groups, and factor(s) other than PBP 2' were suggested to be involved in the methicillin resistance of high-resistance strains. Images PMID:3499861

Optimisation of saponin extraction conditions with Camellia sinensis var. assamica seed and its application for a natural detergent.

PubMed

Gong, Wanying; Huang, Yewei; Ji, Aibing; Peng, Wenshu; Liu, Cong; Zeng, Yin; Yang, Ruijuan; Yan, Liang; Wang, Xuanjun; Sheng, Jun

2018-04-01

Camellia sinensis var. assamica seed cake (a by-product of tea-seed oil) is an abundant resource with poor utilisation. C. sinensis var. assamica seed saponin (CSS) is one kind of non-ionic surfactant. In this study, the CSS extraction conditions were optimised by response surface methodology (RSM) and then the CSS detergent was developed. Additionally, the safety and decontamination ability of the developed detergent were evaluated. The optimised extraction conditions were including the extracting temperature of 40.04 °C, extraction time of 4.97 h, ethanol concentration of 64.11% and liquid-solid ratio of 14.57:1 mL g -1 . The formula of the CSS detergent was as follows: 20% crude CSS, 0.3% oxidised tea polyphenols (OTPs), 0.2% nisin, 0.3% sodium dehydroacetate, 0.7% sodium alginate and 0.5% sodium polyacrylate. The LD 50 of the CSS detergent exceeds 14 g kg -1 in mice, indicating the detergent was non-toxic. Both of the emulsifying and the pesticide residues removal abilities of the CSS detergent were significantly stronger than the commercial detergent. A natural tea seed saponin detergent with good safety and decontamination ability was successfully developed. This can make better use of the tea seed cake, thereby creating added value in the tea seed oil industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

[Pharmacokinetic and clinical experience with flomoxef in bacterial infection in children].

PubMed

Hosoda, T; Ichioka, T; Miyao, M

1987-08-01

Pharmacokinetic and clinical studies were performed on flomoxef (FMOX, 6315-S), a new oxacephem antibiotic, as follows. 1. Pharmacokinetics Serum concentrations of FMOX were measured in 2 cases given 20 mg/kg bolus injection. In the 2 cases, peak concentrations of the drug were 44.3 and 197 micrograms/ml at 15 minutes, T1/2 (beta) were 0.76 and 0.47 hour and AUC were 44.8 and 169.5 micrograms.hr/ml, respectively. Urinary recovery rates for these cases during 6 hours were 83.1 and 54.9%, respectively. The extremely high peak serum concentration in one case may be attributed to dehydration. 2. Clinical efficacy FMOX was administrated intravenously to 12 patients, 6 with pneumonia, 2 with cellulitis, 1 each with bronchitis, tonsillitis, purulent lymphadenitis and subcutaneous abscess, in doses of 55.0-120.0 mg/kg (average 82.2 mg/kg) t.i.d. for 4-13 days (average 6.2 days). The overall efficacy rate was 100%, with excellent responses in 10 and good in 2. Bacteriological efficacy was excellent; 4 of 5 strains were eradicated and 1 strain was decreased. No clinical side effect was observed. Laboratory abnormality was observed in 1 case with transient eosinophilia. The above results suggested that FMOX would be an useful antibiotic for treating pediatric bacterial infections.

Triterpenoid saponins from the roots of Clematis argentilucida.

PubMed

Zhao, Mei; Ma, Ning; Qiu, Feng; Tian, Xiangrong; Zhang, Yan; Tang, Haifeng; Liu, Xinyou

2014-09-01

Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men.

PubMed

Neychev, V K; Mitev, V I

2005-10-03

The aim of the current study is to investigate the influence of Tribulus terrestris extract on androgen metabolism in young males. Twenty-one healthy young 20-36 years old men with body weight ranging from 60 to 125 kg were randomly separated into three groups-two experimental (each n=7) and a control (placebo) one (n=7). The experimental groups were named TT1 and TT2 and the subjects were assigned to consume 20 and 10 mg/kg body weight per day of Tribulus terrestris extract, respectively, separated into three daily intakes for 4 weeks. Testosterone, androstenedione and luteinizing hormone levels in the serum were measured 24 h before supplementation (clear probe), and at 24, 72, 240, 408 and 576 h from the beginning of the supplementation. There was no significant difference between Tribulus terrestris supplemented groups and controls in the serum testosterone (TT1 (mean+/-S.D.: 15.75+/-1.75 nmol/l); TT2 (mean+/-S.D.: 16.32+/-1.57 nmol/l); controls (mean+/-S.D.: 17.74+/-1.09 nmol/l) (p>0.05)), androstenedione (TT1 (mean+/-S.D.: 1.927+/-0.126 ng/ml); TT2 (mean+/-S.D.: 2.026+/-0.256 ng/ml); controls (mean+/-S.D.: 1.952+/-0.236 ng/ml) (p>0.05)) or luteinizing hormone (TT1 (mean+/-S.D.: 4.662+/-0.274U/l); TT2 (mean+/-S.D.: 4.103+/-0.869U/l); controls (mean+/-S.D.: 4.170+/-0.406U/l) (p>0.05)) levels. All results were within the normal range. The findings in the current study anticipate that Tribulus terrestris steroid saponins possess neither direct nor indirect androgen-increasing properties. The study will be extended in the clarifying the probable mode of action of Tribulus terrestris steroid saponins.

Penetration of flomoxef into human maxillary and mandibular bones.

PubMed

Igawa, H H; Sugihara, T; Yoshida, T; Kawashima, K; Ohura, T

1995-09-01

Penetration of flomoxef into the maxillary and mandibular bones was assayed clinically to provide data about its usefulness for the prevention of postoperative infection after maxillofacial surgery. Twenty-one patients undergoing maxillofacial surgery at our department were given flomoxef 2 g dissolved in 20 ml of physiological saline intravenously over 3 minutes during operation, and the serum, maxillary and mandibular concentrations were measured 1, 3, and 6 hours after injection by the band culture method using Escherichia coli 7437 as the indicator strain. The mean concentrations were 53.4, 16.1, and 2.6 micrograms/ml, respectively, in the serum, 17.6, 7.8, and 1.0 micrograms/g in maxillary bone, and 16.4, 4.2, and 0.9 micrograms/g in mandibular bone. The mean bone:serum ratios at 1, 3, and 6 hours were 33.0%, 48.2%, and 36.8%, respectively, for maxillary bone, and 30.7%, 26.2%, and 35.7% for mandibular bone. When compared with previously reported data on the bone:serum ratios in jaw of various other intravenous antibiotics, our results show that penetration of flomoxef into maxillary and mandibular bone is extremely high. As all the intramaxillary and intramandibular concentrations exceed its MIC80 values against clinical isolates of bacteria frequently isolated in cases of infection in the oral and maxillofacial region, it is apparent that one intravenous shot of flomoxef 2 g allows penetration of the drug into the maxillary and mandibular bones at effective concentrations. Flomoxef is therefore potentially useful for the prevention and treatment of infections in the oral and maxillofacial region, as it has excellent penetration into the maxillary and mandibular bones.

[Pharmacokinetic and clinical studies of flomoxef in the perinatal period].

PubMed

Matsuda, S; Hirayama, H; Oh, K; Tamate, K; Sengoku, K; Ishikawa, M; Shimizu, T; Haga, H; Hasegawa, T; Takada, H

1993-07-01

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out and following results were obtained 1. The pharmacokinetic parameter T1/2's of FMOX in maternal serum, umbilical cord serum and amniotic fluid in mothers after single intravenous injection of 1 g (n = 46) and 2 g (n = 34) were 1.11, 9.24, 9.24 hours and 2.54, 12.49, 12.49 hours, respectively. Cmax's and Tmax's of umbilical cord serum and amniotic fluid were 12.71, 11.77 micrograms/ml and 0.57, 3.35 hours upon single dose of 1 g i.v., and 35.17, 12.37 micrograms/ml and 0.32, 3.42 hours upon single dose of 2 g i.v., respectively. 2. Clinical usefulness were evaluated in 93 cases including were various infections in pregnancy and puerperal period. In pregnancy cases, clinical efficacy rate was 95.5% (21/22), and 100% in puerperal period. Bacteriological response rate was 84.6% (eradicated: 29, decreased: 4, unchanged: 2, replaced: 4 and unknown: 8 cases). No severe side effects nor clinical laboratory test results were observed in any cases. From above basic and clinical results, we conclude that FMOX is a useful and safe agent for various infections in pregnancy and puerperal period.

Preparation of progenin III from total steroidal saponins of Dioscorea nipponica Makino using a crude enzyme from Aspergillus oryzae strain.

PubMed

Liu, Tingqiang; Yu, Hongshan; Liu, Chunying; Bao, Yongming; Hu, Xiangchun; Wang, Yuanhao; Liu, Bing; Fu, Yaoyao; Tang, Sihui; Jin, Fengxie

2013-05-01

Progenin III, one of the most active spirostanol saponins, is a potential candidate for anti-cancer therapy due to its strong antitumor activity and low hemolytic activity. However, the concentration of progenin III is extremely low in natural Dioscorea plants. In this paper, the progenin III production from total steroidal saponins of Dioscorea nipponica Makino was studied using the crude enzyme from Aspergillus oryzae DLFCC-38. The crude enzyme converting total steroidal saponins into progenin III was obtained from the A. oryzae DLFCC-38 culture. For enzyme production, the strain was cultured for 72 h at 30 °C with shaking at 150 rpm in 5 % (w/v) malt extract medium containing 2 % (v/v) extract of D. nipponica as the enzyme inducer. The crude enzyme converted total steroidal saponins into major progenin III with a high yield when the reaction was carried out for 9 h at 50 °C and pH 5.0 with the 20 mg/ml of substrate. In the preparation of progenin III, 117 g of crude progenin III was obtained from 160 g of substrate, and the crude product was purified with silica gel column to obtain 60.3 g progenin III of 93.4 % purity.

Antiinflammatory triterpenoid saponins from the seeds of Aesculus chinensis.

PubMed

Wei, Feng; Ma, Lin-Yun; Jin, Wen-Tao; Ma, Shuang-Cheng; Han, Guo-Zhu; Khan, Ikhlas Ahmad; Lin, Rui-Chao

2004-10-01

Phytochemical study of the ethanol extract of the seeds of Aesculus chinensis led to the isolation of a new triterpenoid saponin (6), together with five known triterpenoid saponins (1-5). The structure of the new compound was elucidated on the basis of spectral data to be 21,28-di-O-acetylprotoaescigenin-3-O-[beta-D-glucopyranosyl(1-2)][beta-D-glucopyranosyl(1-4)]-beta-D-glucopyranosiduronic acid (aesculiside A, 6). The antiinflammatory activities of the four main saponins (1-4) were compared with those of total saponin extracts, and single saponins showed more potent activity than total saponin extracts in mice.

Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

PubMed

Färkkilä, M A; Kairemo, K J; Taavitsainen, M J; Strandberg, T A; Miettinen, T A

1996-04-01

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania.

PubMed Central

Chen, M; Christensen, S B; Blom, J; Lemmich, E; Nadelmann, L; Fich, K; Theander, T G; Kharazmi, A

1993-01-01

Licochalcone A, an oxygenated chalcone isolated from the roots of Chinese licorice plant, inhibited the growth of both Leishmania major and Leishmania donovani promastigotes and amastigotes. The structure of the licochalcone A was established by mass and nuclear magnetic resonance spectroscopies and by synthesis, and its purity was verified by high-pressure liquid chromatography. The 50% inhibition of growth of logarithmic- and stationary-phase promastigotes of L. major, as measured by [3H]thymidine uptake, were 4 and 2.5 micrograms/ml, respectively. The growth of L. major promastigotes was totally inhibited after a 20-h incubation period with licochalcone A at 5 micrograms/ml. At a concentration of 0.5 microgram/ml, licochalcone A markedly reduced the infection rate of human peripheral blood monocyte-derived macrophages and U937 cells with L. major promastigotes and exhibited a strong intracellular killing of the parasite. These data show that intracellular Leishmania amastigotes are more susceptible than promastigotes to licochalcone A. Results of studies on the site of action of licochalcone A indicate that the target organelle appears to be the parasite mitochondria. These findings demonstrate that licochalcone A in concentrations that are nontoxic to host cells exhibits a strong antileishmanial activity and that appropriate substituted chalcones might be a new class of antileishmanial drugs. Images PMID:8109916

Modificatory effect of vitamin C and vitamin B-complex on meiotic inhibition induced by organophosphorus pesticide in mice Mus musculus.

PubMed

Hoda, Q; Azfer, M A; Sinha, S P

1993-01-01

Administration of organophosphorous pesticide Malathion and Rogor (both @ 0.2 micrograms/kg body wt/day) upto ten days was found to decrease the division rate in the primary spermatocytes of mice. The concurrent administration of vitamin B-complex (0.3 ml of 1% polybion) or ascorbic acid (0.25 ml of 1% Redoxon) with the pesticide could nullify the meiotic inhibition caused by the pesticides. The vitamins were not found to produce any significant effect on the division rate. Possible mechanism(s) behind this vitamin mediated nullification of meiotic inhibition are discussed.

[Pharmacokinetics and clinical evaluations on aztreonam in perinatal infections in obstetrics and gynecology. A study of aztreonam in the perinatal co-research group].

PubMed

Matsuda, S; Oh, K; Hirayama, H; Shimizu, T; Sengoku, K; Haga, H; Inoue, R; Yamazaki, T; Mizoguchi, H; Tori-i, Y

1990-04-01

Pharmacokinetics and clinical studies on an injectable monobactam antibiotic aztreonam (AZT), were carried out in perinatal infections in obstetrics and gynecology and the obtained results are summarized as follows. 1. Pharmacokinetic study (1) Upon one-shot intravenous injection of AZT 1 g before delivery, maternal serum concentration of AZT was 89.0 micrograms/ml immediately after the injection and a half-life (T 1/2) of 0.96 hour was observed. Umbilical-cord serum concentration showed a peak value of 16.5 micrograms/ml at 1.26 hours after the injection and gradually decreased with a T 1/2 of 1.91 hours. The transfer into amniotic fluid was observed and the peak value of AZT in amniotic fluid reached 12.9 micrograms/ml at 5.57 hours after the injection and slowly decreased thereafter with a T 1/2 of 4.42 hours. Transfer and disappearance in one-shot 2 g intravenous injection and 1 g intravenous drip infusion (1 hour) of AZT were very similar to the results obtained with the one-shot 1 g intravenous injection. (2) The residual serum concentration in neonates after one-shot 1 g intravenous injection of AZT to the mother was almost below the detectable limit. Transfer of AZT into milk was scarcely recognized. 2. Clinical studies (1) AZT was injected to 47 cases with various perinatal infections and it was more than "effective" in 45 cases with an efficacy rate of 95.7%. Also, all the 12 cases to which AZT was administered for prophylaxis of infections showed prophylactic effect. Bacterial eradication was obtained with 25 strains out of 29 aerobic Gram-negative bacteria, but 1 strain "persisted" and for 3 strains results were "unknown", hence an eradication rate of 96.2% was obtained. However, AZT treatment resulted in a little lower eradication rate against Gram-positive bacteria. (2) One case (1.3%) of minor degree of urticaria was found as a side effect, and one case each of eosinophilia and elevation of GOT, GPT and Al-P was observed as abnormal laboratory value. From the above results of pharmacokinetics and clinical evaluation, it has been concluded that AZT is a useful and highly safe drug in various perinatal infections and prophylaxis.

Factors influencing the accumulation of ciprofloxacin in Pseudomonas aeruginosa.

PubMed Central

Celesk, R A; Robillard, N J

1989-01-01

Ciprofloxacin accumulation in Pseudomonas aeruginosa was measured by a bioassay. Drug accumulation in strain PAO2 was compared with that of three spontaneous ciprofloxacin-resistant mutants selected with 0.5 micrograms of ciprofloxacin per ml. PAO4701 cfxA2 contains a mutation in the gyrA gene, PAO4742 cfxB5 may represent a permeability mutant based on pleiotropic drug resistance, and PAO4700 cfxA1 cfxB1 contains both types of mutations. In all strains, drug accumulation was similar, reaching steady state during the first minute of exposure. Drug accumulation was unsaturable over a range of 5 to 80 micrograms/ml, suggesting that ciprofloxacin accumulates by diffusion in P. aeruginosa. Although all four strains accumulated two- to sevenfold more ciprofloxacin in the presence of the inhibitor carbonyl cyanide m-chlorophenylhydrazone, the cfxB mutants accumulated two- to fourfold less drug than either PAO2 or the cfxA2 mutant. Polyacrylamide gel analysis revealed a protein common to cfxB mutants only, while all strains had similar lipopolysaccharide profiles. The results suggest that ciprofloxacin accumulation in P. aeruginosa is a complex phenomenon that may be affected by both an energy-dependent drug efflux process and outer envelope composition. Images PMID:2514623

Paradox between the responses of Escherichia coli K1 to ampicillin and chloramphenicol in vitro and in vivo.

PubMed

Kim, K S; Manocchio, M; Anthony, B F

1984-11-01

We evaluated the activity of ampicillin and chloramphenicol in vitro and in vivo against an Escherichia coli K1 strain. In vitro, the strain was relatively susceptible to both antibiotics (MIC and MBC of ampicillin, 2 and 4 micrograms/ml; MIC and MBC of chloramphenicol, 4 and 64 micrograms/ml). Checkerboard determinations of MBCs of drug combinations were consistent with antibiotic antagonism. Killing curves with concentrations of antibiotics similar to in vivo levels in blood and cerebrospinal fluid of infected rats indicated antagonism within the first 4 h and an indifferent effect of the combination at 24 h. Paradoxically, the combination was significantly more effective than ampicillin or chloramphenicol alone in vivo in infant rats. This was shown by (i) more rapid bacterial clearance from the blood and cerebrospinal fluid, (ii) a decreased incidence of meningitis in bacteremic animals, and (iii) improved survival. These findings illustrate a divergence between the effects of ampicillin and chloramphenicol against E. coli in vitro and in vivo and suggest that this combination is an effective synergistic regimen in this experimental model of E. coli bacteremia and meningitis.

Antimicrobial and mutagenic activity of some carbono- and thiocarbonohydrazone ligands and their copper(II), iron(II) and zinc(II) complexes.

PubMed

Bacchi, A; Carcelli, M; Pelagatti, P; Pelizzi, C; Pelizzi, G; Zani, F

1999-06-15

Several mono- and bis- carbono- and thiocarbonohydrazone ligands have been synthesised and characterised; the X-ray diffraction analysis of bis(phenyl 2-pyridyl ketone) thiocarbonohydrazone is reported. The coordinating properties of the ligands have been studied towards Cu(II), Fe(II), and Zn(II) salts. The ligands and the metal complexes were tested in vitro against Gram positive and Gram negative bacteria, yeasts and moulds. In general, the bisthiocarbonohydrazones possess the best antimicrobial properties and Gram positive bacteria are the most sensitive microorganisms. Bis(ethyl 2-pyridyl ketone) thiocarbonohydrazone, bis(butyl 2-pyridyl ketone)thiocarbonohydrazone and Cu(H2nft)Cl2 (H2nft, bis(5-nitrofuraldehyde)thiocarbonohydrazone) reveal a strong activity with minimum inhibitory concentrations of 0.7 microgram ml-1 against Bacillus subtilis and of 3 micrograms ml-1 against Staphylococcus aureus. Cu(II) complexes are more effective than Fe(II) and Zn(II) ones. All bisthiocarbono- and carbonohydrazones are devoid of mutagenic properties, with the exception of the compounds derived from 5-nitrofuraldehyde. On the contrary a weak mutagenicity, that disappears in the copper complexes, is exhibited by monosubstituted thiocarbonohydrazones.

Distribution of carbohydrates recognized by the lectins Euonymus europaeus and concanavalin A in monoxenic and heteroxenic trypanosomatids.

PubMed

Gazzinelli, R T; Romanha, A J; Fontes, G; Chiari, E; Gazzinelli, G; Brenner, Z

1991-01-01

We observed a wide distribution of the carbohydrate epitopes galactosyl alpha(1-3)galactose (gal alpha1-3 gal), alpha-glucoside and alpha-mannoside in mono- and heteroxenic trypanosomatids by using fluorescein-labelled lectins of Euonymus europaeus (EE) and Concanavalin A (Con A) as well as sera from acute chagasic patients who have very high levels of anti-gal alpha(1-3)gal antibodies. The direct fluorescence test for gal alpha1-3 gal with EE was positive at minimum concentrations of 6 micrograms/ml for heteroxenic trypanosomatids and 0.7 micrograms/ml for monoxenic ones and for the plant parasite, Phytomonas. On the other hand, heteroxenic trypanosomatids that infect vertebrates bound ten-fold more Con A than monoxenic flagellates and Phytomonas. These data were confirmed in ELISA and Western Blot assays carried out with peroxidase-labelled EE and Con A. Euonymus europaeus recognized several glycoproteins in all trypanosomatids that we tested. Con A, however, recognized a glycoprotein cluster in heteroxenic protozoa, which ranging from 60-120 kDa, seemed to lack monoxenic parasites and Phytomonas. These findings suggest that alpha-D-mannose and alpha-D-glucose might play an important role in the interaction between trypanosomatids and vertebrate hosts.

Two new triterpene saponins from the anti-inflammatory saponin fraction of Ilex pubescens root.

PubMed

Wang, Jing-Rong; Zhou, Hua; Jiang, Zhi-Hong; Liu, Liang

2008-07-01

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti-inflammatory effects on carrageenan-induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20beta)-3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, and (20beta)-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa- 12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B(1), B(2), B(3), A(1), and chikusetsusaponin IV(a).

Effect of antacids on predicted steady-state cimetidine concentrations.

PubMed

Russell, W L; Lopez, L M; Normann, S A; Doering, P L; Guild, R T

1984-05-01

The purpose of this study was to evaluate effects of antacids on predicted steady-state concentrations of cimetidine. Ten healthy volunteers received in random order one week apart, cimetidine and cimetidine and antacid suspension. Blood was obtained at specified times and analyzed for cimetidine. Bioavailability was assessed by comparison of peak concentration, time to peak concentration, area under the curve, and time spent over 0.5 micrograms/ml. Single-dose data were extrapolated to steady-state using computer simulation. Concurrent administration of antacid suspension reduced parameters of bioavailability approximately 30%. When steady-state conditions were simulated, concentrations of cimetidine greater than or equal to 0.5 micrograms/ml were maintained for the entire dosing interval in seven of 10 subjects. These data suggest that temporal separation of cimetidine and antacid suspension may be unnecessary.

Vaginal oxytetracycline concentrations.

PubMed Central

Thin, R N; Al Rawi, Z H; Simmons, P D; Treharne, J; Tabaqchali, S

1979-01-01

Although tetracycline preparations are widely used in departments of genitourinary medicine, or sexually transmitted diseases clinics, little is known of the concentrations of these preparations in genital secretions. For this reason a microbiological method was used for estimating oxytetracycline concentrations in vaginal secretions. These concentrations varied from 0.6 to 6.5 microgram/ml in 19 women who had had sexual contact with a man with non-specific urethritis and who were taking oxytetracycline dihydrate 250 mg four times daily. They were well in excess of the minimum inhibitory concentration of oxytetracycline (0.2 microgram/ml) for the strains of Chlamydia trachomatis isolated from the patients with positive culture results. Thus, oxytetracycline 250 mg four times daily appears to be a satisfactory regimen for the treatment of chlamydial genital infection in women. PMID:509190

[Differential action of non-steroidal antiinflammatory drugs on human gallbladder cyclooxygenase and lipoxygenase].

PubMed

Franchi, A; Di Girolamo, G; Farina, M; de los Santos, A R; Martí, M L; Gimeno, M A

2000-01-01

Lysine clonixinate (LC) is a non-steroidal antiinflammatory agent (NSAID) with only few adverse effects. This characteristic has prompted us to suggest that its administration, at levels equivalent to those found in human plasma following therapeutic doses, slightly inhibits cyclooxygenase I (COX I). Three experiments were performed. Experiment 1: to study the in vitro effect of LC at concentrations of 4 and 6 micrograms/ml, comparable with those found in plasma following an oral therapeutic dose of 125 mg. Gallbladder tissue segments were incubated with 0.25 microCi of 14C-arachidonic acid and the production of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was measured. LC did not affect basal production of any of the 3 prostaglandins (PGs) but at 6 micrograms/ml slightly reduced the levels of 5-hidroxyeicosatetraenoic acid (5-HETE). Experiment 2: LC was administered preoperatively to 6 patients by continuous perfusion, to achieve a steady-state concentration between 4 and 6 micrograms/ml. Gallbladder segments from the 6 treated and another 6 control patients were incubated in 14C-arachidonic acid. Gallbladder segments treated with LC did not show a decreased production of any of the three PGs whereas 5-HETE released to the medium was significantly lower. Experiment 3: 18 patients received an i.v. bolus of LC 100 mg (n1 = 6) or LC 200 mg (n2 = 6) or indomethacin (INDO) 50 mg (n3 = 6). Unlike the administration of INDO bolus, LC in the above doses did not inhibit PG synthesis. Both NSAIDs showed different effects when the production of 5-HETE synthesis was assessed. Treatment with INDO did not alter the production of 5-HETE while LC elicited significant inhibition. The three studies conducted, namely in vitro and in vivo continuous perfusion and i.v. bolus, revealed that LC had no effect on prostaglandin synthesis while reducing significantly the levels of 5-HETE.

Influence of spaceflight on the production of interleukin-3 and interleukin-6 by rat spleen and thymus cells

NASA Technical Reports Server (NTRS)

Miller, Edwin S.; Koebel, D. Anne; Sonnefeld, Gerald

1995-01-01

Six adult male Sprague-Dawley rats were flown on the 7-day US space shuttle mission STS-54. After flight, the spleen and thymus from each animal were assayed for the capacity to secrete the cytokines interleukin-3 (IL-3) and IL-6. Spleen and thymus cells were incubated for 48 h in the presence of 5 microgram/ml of concanavalin A or 2 microgram/ml of bacterial lipopolysaccharide to stimulate the production of IL-3 and IL-6. IL-3 activity was measured using the IL-3/colony-stimulating-factor-dependent cell line 32D. IL-6 activity was measured using the IL-6-dependent cell line 7TD1. Spleen and thymus cells harvested from flown rats secreted significantly higher titers of biologically active IL-3 compared with ground control rats. Spaceflight significantly enhanced IL-6 production by thymus, but not spleen, cells. The results of this study demonstrate that spaceflight can enhance the production of certain cytokines by cells of the immune system.

Determination of Four Major Saponins in Skin and Endosperm of Seeds of Horse Chestnut (Aesculus Hippocastanum L.) Using High Performance Liquid Chromatography with Positive Confirmation by Thin Layer Chromatography.

PubMed

Abudayeh, Zead Helmi Mahmoud; Al Azzam, Khaldun Mohammad; Naddaf, Ahmad; Karpiuk, Uliana Vladimirovna; Kislichenko, Viktoria Sergeevna

2015-11-01

To separate and quantify four major saponins in the extracts of the skin and the endosperm of seeds of horse chestnut (Aesculus hippocastanum L.) using ultrasonic solvent extraction followed by a high performance liquid chromatography-diode array detector (HPLC-DAD) with positive confirmation by thin layer chromatography (TLC). The saponins: escin Ia, escin Ib, isoescin Ia and isoescin Ib were extracted using ultrasonic extraction method. The optimized extraction conditions were: 70% methanol as extraction solvent, 80 °C as extraction temperature, and the extraction time was achieved in 4 hours. The HPLC conditions used: Zorbax SB-ODS-(150 mm × 2.1 mm, 3 μm) column, acetonitrile and 0.10% phosphoric acid solution (39:61 v/v) as mobile phase, flow rate was 0.5 mL min(-1) at 210 nm and 230 nm detection. The injection volume was 10 μL, and the separation was carried out isothermally at 30 °C in a heated chamber. The results indicated that the developed HPLC method is simple, sensitive and reliable. Moreover, the content of escins in seeds decreased by more than 30% in endosperm and by more than 40% in skin upon storage for two years. This assay can be readily utilized as a quality control method for horse chestnut and other related medicinal plants.

The use of emulsions for the determination of methylmercury and inorganic mercury in fish-eggs oil by cold vapor generation in a flow injection system with atomic absorption spectrometric detection.

PubMed

Burguera, J L; Quintana, I A; Salager, J L; Burguera, M; Rondón, C; Carrero, P; Anton de Salager, R; Petit de Peña, Y

1999-04-01

An on-line time based injection system used in conjunction with cold vapor generation atomic absorption spectrometry and microwave-aided oxidation with potassium persulfate has been developed for the determination of the different mercury species in fish-eggs oil samples. A three-phase surfactant-oil-water emulsion produced an advantageous flow when a peristaltic pump was used to introduce the highly viscous sample into the system. The optimum proportion of the oil-water mixture ratio was 2:3 v/v with a Tween 20 surfactant concentration in the emulsion of 0.008% v/v. Inorganic mercury was determined after reduction with sodium borohydride while total mercury was determined after an oxidation step with persulfate prior to the reduction step to elemental mercury with the same reducing agent. The difference between total and inorganic mercury determined the organomercury content in samples. A linear calibration graph was obtained in the range 0.1-20 micrograms l-1 of Hg2+ by injecting 0.7 ml of samples. The detection limits based on 3 sigma of the blank signals were 0.11 and 0.12 microgram l-1 for total and inorganic mercury, respectively. The relative standard deviation of ten independent measurements were 2.8 and 2.2% for 10 micrograms l-1 and 8.8 and 9.0% for 0.1 microgram l-1 amounts of total and inorganic mercury, respectively. The recoveries of 0.3, 0.6 and 8 micrograms l-1 of inorganic and organic mercury added to fish-eggs oil samples ranged from 93.0 to 94.8% and from 100 to 106%, respectively. Good agreement with those values obtained for total mercury content in real samples by electrothermal atomic absorption spectrometry was also obtained, differences between mean values were < 7%. With the proposed procedure, 22 proteropterous catfish-eggs oil samples from the northwestern coast of Venezuela were measured; while the organic mercury lay in the range 2.0 and 3.3 micrograms l-1, inorganic mercury was not detected.

Multihormonal regulation of thyroglobulin production by the OVNIS 6H thyroid cell line.

PubMed

Aouani, A; Hovsépian, S; Fayet, G

1988-02-01

The hormonal regulation of thyroglobulin production has been studied using a clone of the ovine thyroid cell line: OVNIS 6H. 3 among the 6 hormones proposed for serum replacement are required for an optimal thyroglobulin production; insulin, hydrocortisone and thyrotropin. Insulin alone stimulates thyroglobulin production. The presence of insulin is also required to observe hydrocortisone and TSH stimulations. Newborn calf serum inhibits thyroglobulin production. The best conditions for optimal thyroglobulin expression and TSH responsiveness are obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

Selective activity of several cholic acid derivatives against human immunodeficiency virus replication in vitro.

PubMed

Baba, M; Schols, D; Nakashima, H; Pauwels, R; Parmentier, G; Meijer, D K; De Clercq, E

1989-01-01

Several cholic acid derivatives such as taurolithocholic acid, lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate were shown to inhibit selectively the replication of human immunodeficiency virus type 1 (HIV-1) in vitro. These compounds completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 100 micrograms/ml, whereas no toxicity for the host cells was observed at 200 micrograms/ml. They also inhibited HIV-1 antigen expression in HIV-1-infected CEM cells. The bile acids (cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid) did not show any inhibitory effect on HIV-1 replication at concentrations that were not toxic to the host (MT-4) cells. From a structure-function analysis of a number of cholic acid derivatives, the presence of either a sulfonate (as in the tauro conjugates) or a sulfate group as well as the "litho" configuration appeared to be necessary for the expression of anti-HIV-1 activity. The active cholic acid derivatives did not directly inactivate the virus particles at the concentrations that were not toxic to the host cells. Lithocholic acid 3-sulfate, taurolithocholic acid 3-sulfate, and glycolithocholic acid 3-sulfate, but not taurolithocholic acid, partially inhibited virus adsorption to MT-4 cells. These three compounds were also inhibitory to the reverse transcriptase activity associated with HIV-1.

Comparison of saponin composition and content in wild soybean (Glycine soja Sieb. and Zucc.) before and after germination.

PubMed

Krishnamurthy, Panneerselvam; Tsukamoto, Chigen; Takahashi, Yuya; Hongo, Yuji; Singh, Ram J; Lee, Jeong Dong; Chung, Gyuhwa

2014-01-01

Eight wild soybean accessions with different saponin phenotypes were used to examine saponin composition and relative saponin quantity in various tissues of mature seeds and two-week-old seedlings by LC-PDA/MS/MS. Saponin composition and content were varied according to tissues and accessions. The average total saponin concentration in 1 g mature dry seeds of wild soybean was 16.08 ± 3.13 μmol. In two-week-old seedlings, produced from 1 g mature seeds, it was 27.94 ± 6.52 μmol. Group A saponins were highly concentrated in seed hypocotyl (4.04 ± 0.71 μmol). High concentration of DDMP saponins (7.37 ± 5.22 μmol) and Sg-6 saponins (2.19 ± 0.59 μmol) was found in cotyledonary leaf. In seedlings, the amounts of group A and Sg-6 saponins reduced 2.3- and 1.3-folds, respectively, while DDMP + B + E saponins increased 2.5-fold than those of mature seeds. Our findings show that the group A and Sg-6 saponins in mature seeds were degraded and/or translocated by germination whereas DDMP saponins were newly synthesized.

Mycotoxin producing potential of some isolates of Aspergillus flavus and Eurotium groups from meat products.

PubMed

el-Kady, I; el-Maraghy, S; Zohri, A N

1994-09-01

All strains (92) of A. flavus group proved to be positive for production of aflatoxin (45 to 1200 micrograms/50 ml medium) on potato dextrose liquid medium, while 59 strains only proved to be positive (35-310 micrograms/50 ml) on 15% NaCl potato-dextrose liquid medium. Most of the strains tested of A. flavus, A. flavus var. columnaris and A. oryzae produced aflatoxins B1, B2, G1 & G2. All positive strains of A. tamarii produced aflatoxins G1 & G2 while the tested isolate of A. zonatus produced aflatoxins B1 & G1. Of 95 strains tested of Eurotium, aflatoxins B1 & G1 were produced by one strain of each of E. chevalieri var. intermedium, E. repens and E. rubrum. Gliotoxin was detected in the extract of two strains of E. chevalieri and one strain of each of E. chevalieri var. intermedium and E. pseudoglaucum on the salt-free medium, and two strains of each of E. chevalieri, E. chevalieri var. intermedium and one of E. pseudoglaucum on 15% NaCl medium. Sterigmatocystin was produced by some strains of E. chevalieri, E. chevalieri var. intermedium, E. amstelodami, E. pseudoglaucum and E. rubrum on the two experimental media. One strain only of E. repens produced ochratoxin A while citrinin was detected in the extract of one strain of E. pseudoglaucum.

Respiratory disease rates and pulmonary function in children associated with NO2 exposure.

PubMed

Speizer, F E; Ferris, B; Bishop, Y M; Spengler, J

1980-01-01

As part of a long-range, prospective study of the health effects of air pollution, approximately 8,000 children from 6 yrs to 10 yrs of age from 6 communities had questionnaires completed by their parents and had simple spirometry performed in school. Comparisons were made between children living in homes with gas stoves and those living in homes with electric stoves. Children from households with gas stoves had a greater history of respiratory illness before age 2 (average difference, 32.5/1,000 children) and small but significantly lower levels of FEV1 and FVC corrected for height (average difference, 16 ml and 18 ml, respectively). These findings were not explained by differences in social class or by parental smoking habits. Measurements taken in the homes for 24-h periods showed that NO2 levels were 4 to 7 times higher in homes with gas stoves than in homes with electric stoves. However, these 24-h measurements were generally well below the current federal 24-h outdoor standard of 100 micrograms/m3. Short-term peak exposures, which were in excess of 1,100 micrograms/m3, regularly occurred in kitchens. Further work will be required to determine the importance of these short-term peaks in explaining the effects noted.

Idiopathic hypercalciuria with bilateral macular colobomata: a new variant of oculo-renal syndrome.

PubMed

Meier, W; Blumberg, A; Imahorn, W; De Luca, F; Wildberger, H; Oetliker, O

1979-01-01

Two siblings from a consanguineous family, suffering from nephrocalcinosis and nephrolithiasis caused by idiopathic hypercalciuria are described. The condition is associated with bilateral macular colobomata and tapeto-retinal degeneration. It is known that the latter can occur together with different nephropathies; however, until now it has never been described in combination with idiopathic hypercalciuria. Blood calcium levels were found to be normal, calcium excretion rates were, with one exception, more than 6 mg/kg/24 h corrected for 100 ml GFR. Hypomagnesemia of 1.5 and 1.2 mg/dl and hyermagnesuria of 1.9 and 2.5 mg/kg/24 h corrected for 100 ml GFR were found in both patients. Tubular phosphate reabsorption reached 87% and 84% at serum parathormone levels of 0.34 microgram/l and 0.31 microgram/l in the two patients, respectively. Under calcium and magnesium loading the clearance rates of calcium and magnesium were raised whilst there was only a small insignificant increase in the blood levels of these cations. Acid-base titrations showed normal excretion rates of acid and base in one patient and a mild proximal tubular acidosis in the other. Quantitative investigation of the renal concentrating and diluting capacity established a decrease in the formation of the medullary concentrating gradient in both patients.

Effect of urban stormwater runoff on ground water beneath recharge basins on Long Island, New York

USGS Publications Warehouse

Ku, H.F.; Simmons, D.L.

1986-01-01

Urban stormwater runoff was monitored during 1980-82 to investigate the source, type, quantity, and fate of contaminants routed to the more than 3,000 recharge basins on Long Island and to determine whether this runoff might be a significant source of contamination to the groundwater reservoir. Forty-six storms were monitored at five recharge basins in representative land use areas (strip commercial, shopping-mall parking lot, major highway, low-density residential, and medium-density residential). Runoff:precipitation ratios indicate that all storm runoff is derived from precipitation on impervious surfaces in the drainage area, except during storms of high intensity or long duration, when additional runoff can be derived from precipitation on permeable surfaces. Lead was present in highway runoff in concentrations up to 3300 micrograms/L, and chloride was found in parking lot runoff concentrations up to 1,100 mg/L during winter, when salt is used for deicing. In the five composite stormwater samples and nine groundwater grab samples that were analyzed for 113 EPA-designated ' priority pollutants, ' four constituents were detected in concentrations exceeding New York State guidelines of 50 micrograms/L for an individual organic compound in drinking water: p-chloro-m-cresol (79 micrograms/L); 2 ,4-dimethylphenol (96 micrograms/L); 4-nitrophenol (58 micrograms/L); and methylene chloride (230 micrograms/L in either groundwater or stormwater at the highway basin). One stormwater sample and two groundwater samples exceeded New York State guidelines for total organic compounds in drinking water (100 micrograms/L). The presence of these constituents is attributed to contamination from point sources rather than to the quality of runoff from urban areas. The median number of indicator bacteria in stormwater ranged from 0.1 to 10 billion MPN/100 ml. Fecal coliforms and fecal streptococci increased by 1 to 2 orders of magnitude during the warm season. The use of recharge basins to dispose of storm runoff does not appear to have significant adverse effects on groundwater quality in terms of the chemical and microbiological stormwater constituents studied. (Author 's abstract)

Inductively coupled plasma atomic emission spectrometric determination of tin in canned food.

PubMed

Sumitani, H; Suekane, S; Nakatani, A; Tatsuka, K

1993-01-01

Various canned foods were digested sequentially with HNO3 and HCl, diluted to 100 mL, and filtered, and then tin was determined by inductively coupled plasma atomic emission spectrometry (ICP/AES). Samples of canned Satsuma mandarin, peach, apricot, pineapple, apple juice, mushroom, asparagus, evaporated milk, short-necked clam, spinach, whole tomato, meat, and salmon were evaluated. Sample preparations did not require time-consuming dilutions, because ICP/AES has wide dynamic range. The standard addition method was used to determine tin concentration. Accuracy of the method was tested by analyzing analytical standards containing tin at 2 levels (50 and 250 micrograms/g). The amounts of tin found for the 50 and 250 micrograms/g levels were 50.5 and 256 micrograms/g, respectively, and the repeatability coefficients of variation were 4.0 and 3.8%, respectively. Recovery of tin from 13 canned foods spiked at 2 levels (50 and 250 micrograms/g) ranged from 93.9 to 109.4%, with a mean of 99.2%. The quantitation limit for tin standard solution was about 0.5 microgram/g.

[The airborne 1,3-butadiene concentrations in rubber and plastic processing plants].

PubMed

Yoshida, Toshiaki; Tainaka, Hidetsugu; Matsunaga, Ichiro; Goto, Sumio

2002-03-01

Environment pollution by 1,3-butadiene had considerably increased in Japan. The main cause of the pollution is the automotive exhaust gas, and leaks from factories, smoking, and burning of rubber and plastic products are considered to be minor sources. The object of this study was to determine the contamination levels of airborne 1,3-butadiene in factories processing rubber and plastics containing 1,3-butadiene. The concentrations of airborne 1,3-butadiene were measured in 21 plants (10 rubber processing plants and 11 plastics processing plants) in Osaka. 1,3-Butadiene in air was collected for 10 minutes with a charcoal tube and a portable small pump adjusted to a 250 ml/min flow rate. In each plant, indoor air samples at five points and an outdoor air sample at one point outside the plant were collected. The samples were subjected to gas chromatography/mass spectrometry after thermal desorption from the charcoal. The concentrations of airborne 1,3-butadiene in the rubber processing plants and the plastics processing plants were 0.14-2.20 micrograms/m3 (geometric mean: 0.48 microgram/m3) and 0.23-4.51 micrograms/m3 (geometric mean: 0.80 microgram/m3), respectively. In all plants examined, indoor 1,3-butadiene concentrations were higher than the outdoor concentrations around the plants. Therefore, 1,3-butadiene was considered to arise from the processing of rubber or plastics, but the indoor 1,3-butadiene concentrations were much lower than the PEL-TWA (1 ppm = 2.21 mg/m3) of OSHA and the TLV-TWA (2 ppm) of ACGIH. The concentrations in the plants with closed room conditions without ventilation were higher than the concentrations in the other plants. It was suggested that ventilation affected the 1,3-butadiene concentration in the plants.

APPROXIMATE ENZYMIC METHOD OF MICROANALYSIS FOR IDENTIFYING RESIDUAL AMOUNTS OF ORGANOPHOSPHORUS INSECTICIDES,

DTIC Science & Technology

plant extracts gradually increases. This is evidently explained by a conversion of the insecticide into a compound possessing high anticholinesterase activity . (Author)...possible to determine from 1 to 100 micrograms of insecticide per 1 ml. It was established that the anticholinesterase activity of chlorphos when...inherent anticholinesterase action, was developed. In order to realize this method a portable kit was constructed which contains a rack for the storage

Nickel absorption and kinetics in human volunteers.

PubMed

Sunderman, F W; Hopfer, S M; Sweeney, K R; Marcus, A H; Most, B M; Creason, J

1989-05-01

Mathematical modeling of the kinetics of nickel absorption, distribution, and elimination was performed in healthy human volunteers who ingested NiSO4 drinking water (Experiment 1) or added to food (Experiment 2). Nickel was analyzed by electrothermal atomic absorption spectrophotometry in serum, urine, and feces collected during 2 days before and 4 days after a specified NiSO4 dose (12 micrograms of nickel/kg, n = 4; 18 micrograms of nickel/kg, n = 4; or 50 micrograms of nickel/kg, n = 1). In Experiment 1, each of the subjects fasted 12 hr before and 3 hr after drinking one of the specified NiSO4 doses dissolved in water; in Experiment 2, the respective subjects fasted 12 hr before consuming a standard American breakfast that contained the identical dose of NiSO4 added to scrambled eggs. Kinetic analyses, using a compartmental model, provided excellent goodness-of-fit for paired data sets from all subjects. Absorbed nickel averaged 27 +/- 17% (mean +/- SD) of the dose ingested in water vs 0.7 +/- 0.4% of the same dose ingested in food (a 40-fold difference); rate constants for nickel absorption, transfer, and elimination were not significantly influenced by the oral vehicle. The elimination half-time for absorbed nickel averaged 28 +/- 9 hr. Renal clearance of nickel averaged 8.3 +/- 2.0 ml/min/1.73 m2 in Experiment 1 and 5.8 +/- 4.3 ml/min/1.73 m2 in Experiment 2. This study confirms that dietary constituents profoundly reduce the bioavailability of Ni2+ for alimentary absorption; approximately one-quarter of nickel ingested in drinking water after an over-night fast is absorbed from the human intestine and excreted in urine, compared with only 1% of nickel ingested in food. The compartmental model and kinetic parameters provided by this study will reduce the uncertainty of toxicologic risk assessments of human exposures to nickel in drinking water and food.

Case study: fatal poisoning by malathion.

PubMed

Thompson, T S; Treble, R G; Magliocco, A; Roettger, J R; Eichhorst, J C

1998-07-20

A case involving a fatal poisoning (suicide) by the insecticide malathion is described. The intact insecticide was found in the post-mortem blood and gastric contents at concentrations of 1.8 and 978 micrograms/ml, respectively. None of the insecticide was found in the autopsied liver tissue. Gas chromatography-mass spectrometry (GC-MS) techniques were used for the identification and quantification of malathion in the body fluids.

Induction of Apoptosis in Human Cancer Cells Through Extrinsic and Intrinsic Pathways by Balanites aegyptiaca Furostanol Saponins and Saponin-Coated SilverNanoparticles.

PubMed

Yassin, Abdelrahman M; El-Deeb, Nehal M; Metwaly, Ahmed M; El Fawal, Gomaa F; Radwan, Mohamed M; Hafez, Elsayed E

2017-08-01

The aim of this investigation is to examine the anticancer activities of Balanites aegyptiaca fruit extract with its biogenic silver nanoparticles (AgNPs) against colon and liver cancer cells. B. aegyptiaca aqueous extract was fractionated according to polarity and by biosynthesized AgNP. The cytotoxicity of the extract, semi-purified fractions, and the AgNPs was examined on noncancerous cell lines. The safer fraction was subjected to ultra-performance liquid chromatography-MS to identify the major active constituents. The anticancer activities of the nontoxic doses of all the used treatments were tested against HepG2 and CaCo2 cells. The nontoxic dose of the B. aegyptiaca (0.63 mg/ml) extract showed high anti-proliferative activities against HepG2 and CaCo2 with a percentage of 81 and 77%, respectively. The butanol fraction was safer than the other two fractions with 46.3 and 90.35% anti-proliferative activity against Caco2 and HepG2 cells, respectively. The nontoxic dose of AgNPs (0.63 mg/ml) inhibits both HepG2 and Caco2 cells with a percentage of 84.5 and 83.4%, respectively. In addition, AgNPs regulate the expression of certain genes with folding higher than that of crude extract. Saponin-coated AgNPs showed great abilities to select the most anticancer ingredient(s) from the B. aegyptiaca extract with a more safety pattern than the polarity gradient fractionation.

Persistent staphylococcal bacteremia in an intravenous drug abuser.

PubMed

Barg, N L; Supena, R B; Fekety, R

1986-02-01

A patient with methicillin-resistant Staphylococcus aureus bacteremia received vancomycin (MIC = 0.8 microgram/ml, MBC = 15 micrograms/ml) and heparin simultaneously through the same intravenous line to treat a septic deep venous thrombosis. Bacteremia persisted for 7 days. Bacteremia terminated when the simultaneous infusion of heparin and vancomycin through the same line was stopped. This suggested that an interaction between vancomycin and heparin may have occurred, which resulted in a reduction in vancomycin activity. To test for such an interaction, mixtures of heparin and vancomycin in various concentrations were made and tested for antimicrobial activity against the organisms in the patient. A precipitate formed at the concentrations achieved in the intravenous lines, and when the vancomycin concentrations were measured by bioassay, a 50 to 60% reduction in activity was noted. In contrast, when these solutions were prepared and mixed at microgram concentrations, a precipitate was no longer observed, and antimicrobial activity was not reduced. Heparin appeared to interact unfavorably with vancomycin at the concentrations in the intravenous lines when these drugs were administered simultaneously to patients. This may be the cause of poor therapeutic responses to vancomycin in some patients, especially those infected with tolerant organisms.

Effect of tea on iron absorption from the typical Tunisian meal 'couscous' fed to healthy rats.

PubMed

Hamdaoui, M; Hedhili, A; Doghri, T; Tritar, B

1994-01-01

Black and green tea decoctions are popular beverages in Tunisia, especially after eating. Our study was performed to examine the effect of graded amounts of black and green tea decoction prepared under realistic Tunisian conditions on nonheme iron absorption from a typical Tunisian meal, 'couscous', by extrinsic radioiron labeling in rats. Concentrations of 300, 200 and 100 micrograms/ml of black tea decreased dramatically nonheme iron bioavailability from couscous, but 50 micrograms/ml did not influence iron absorption. The inhibition of nonheme iron from couscous varied from 36 to 61% with black tea and 30.5% with green tea. Taken together, our findings show that the tea decoction in Tunisia has a great inhibitory power and may constitute an important factor for the development of iron deficiency anemia throughout Tunisia.

Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed.

PubMed

Prasad, K

1997-03-01

Recently there has been a moderate resurgence in the use of flax-seed in a variety of ways including bread. The scientific basis of its use is very limited. There is some claim for beneficial effects in cancer and lupus nephritis. These claims could be due to its ability to scavenge oxygen radicals. However, its antioxidant activity is not known. Recently a method has been developed to isolate secoisolariciresinol diglucoside (SDG) from defatted flax-seed in large quantity (patent pending). We investigated the ability of SDG to scavenge .OH using high pressure liquid chromatography (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10.0 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH-adduct products 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. H2O2 produced a concentration-dependent .OH as estimated by 2,3-DHBA and 2,5-DHBA. A standard curve was constructed for known concentrations of 2,3-DHBA and 2,5-DHBA against corresponding area under the peaks which then was used for measurement of 2,3-DHBA and 2,5-DHBA generated by UV irradiation of H2O2 in the presence of salicylic acid. SDG in the concentration range of 25, 50, 100, 250, 500, 750, 1000 and 2000 micrograms/ml (36.4, 72.8, 145.6, 364.0, 728.0, 1092.0, 1456.0 and 2912.0 microM respectively) produced a concentration-dependent decrease in the formation of 2,3-DHBA and 2,5-DHBA, the inhibition being 4 and 4.65% respectively with 25 micrograms/ml (36.4 microM) and 82 and 74% respectively with 2000 micrograms/ml (2912.0 microM). The decrease in .OH-adduct products was due to scavenging of .OH and not by scavenging of formed 2,3-DHBA and 2,5-DHBA. SDG prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner in the concentration range from 319.3-2554.4 microM. These results suggest that SDG scavenges .OH and therefore has an antioxidant activity.

Furostanol and Spirostanol Saponins from Tribulus terrestris.

PubMed

Wang, Zhen-Fang; Wang, Bing-Bing; Zhao, Yang; Wang, Fang-Xu; Sun, Yan; Guo, Rui-Jie; Song, Xin-Bo; Xin, Hai-Li; Sun, Xin-Guang

2016-03-30

Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin J-T (1-11), and one spirostanol saponin, terrestrinin U (12), together with seven known steroidal saponins 13-19 were isolated from T. terrestris. The structures of the new compounds were established on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS, and comparisons with published data.

Triterpenoid saponins from Echinopsis macrogona (Cactaceae).

PubMed

Okazaki, Sachie; Kinoshita, Kaoru; Ito, Satoru; Koyama, Kiyotaka; Yuasa, Hiroshi; Takahashi, Kunio

2011-01-01

Triterpene saponins, pachanosides C1, E1, F1 and G1 (1-4), and bridgesides A1, C1, C2, D1, D2, E1 and E2 (5-11) were isolated from Echinopsis macrogona. Compounds 1-4 were saponins with pachanane type triterpene saponins, while the others (5-11) were oleanane type triterpene saponins. While the aglycones of 2-4 and 8-11 were hitherto unknown, the structure of pachanol C was revised in this paper. Their structures were elucidated on the basis of chemical and physicochemical evidence. Copyright © 2010 Elsevier Ltd. All rights reserved.

Apical effect of diosmectite on damage to the intestinal barrier induced by basal tumour necrosis factor-alpha.

PubMed Central

Mahraoui, L; Heyman, M; Plique, O; Droy-Lefaix, M T; Desjeux, J F

1997-01-01

BACKGROUND: In many digestive diseases the intestinal barrier is weakened by the release of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF alpha). AIM: To investigate the protective effect of apical diosmectite on the intestinal dysfunction induced by the proinflammatory cytokine TNF alpha. METHODS: Filter grown monolayers of the intestinal cell line HT29-19A were incubated for 48 hours in basal medium containing 10 ng/ml TNF alpha and 5 U/ml interferon-gamma (IFN gamma). Next, 1, 10, or 100 mg/ml diosmectite was placed in the apical medium for one hour. Intestinal function was then assessed in Ussing chambers by measuring ionic conductance (G) and apicobasal fluxes of 14C-mannitol (Jman), and intact horseradish peroxidase. In control intestinal monolayers, diosmectite did not significantly modify G, Jman, or intact horseradish peroxidase. RESULTS: After incubation with TNF alpha and IFN gamma, intestinal function altered, as shown by the increases compared with control values for G (22.8 (3.7) v (9.6 (0.5) mS/cm2), Jman (33.8 (7.5) v 7.56 (0.67) micrograms/h x cm2), and intact horseradish peroxidase (1.95 (1.12) v 0.14 (0.04) micrograms/h x cm2). G and Jman were closely correlated, suggesting that the increase in permeability was paracellular. Treatment with diosmectite restored al the variables to control values. CONCLUSIONS: Basal TNF alpha disrupts the intestinal barrier through the tight junctions, and apical diosmectite counteracts this disruption. PMID:9135522

Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, M.M.; Clark, L.; Armstrong, L.

Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the /sup 51/Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75more » to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients.« less

Hormone levels in vegetarian and nonvegetarian teenage girls: potential implications for breast cancer risk.

PubMed

Persky, V W; Chatterton, R T; Van Horn, L V; Grant, M D; Langenberg, P; Marvin, J

1992-02-01

Between September 1984 and June 1985, a total of 75 adolescent girls, 35 vegetarians residing in a Seventh-Day Adventist school and 40 nonvegetarians residing in a private non-Adventist boarding school, underwent measurement of their plasma hormone levels in the follicular and luteal phase of their menstrual cycles as well as dietary intake measured by 3-day food records, medical history, height, and weight. There were no significant differences between vegetarians and nonvegetarians in average age of the girls, weight, body mass index, age at menarche, years since the onset of menstruation, or percentage of girls with ovulatory cycles. Vegetarian girls had significantly higher levels of log follicular estradiol [2.00 +/- 0.27 (SD) versus 1.85 +/- 0.27 pg/ml, P less than or equal to 0.05] and luteal dehydroepiandrosterone sulfate (DHS) (1.88 +/- 0.71 versus 1.45 +/- 0.80 microgram/ml, P less than or equal to 0.05) than nonvegetarian girls. Follicular DHS was higher in vegetarians than in nonvegetarians (1.72 +/- 0.79 versus 1.45 +/- 0.95 microgram/ml), but the difference was not significant. The differences in follicular and luteal DHS, but not the difference in log estradiol, were significant (P less than or equal to 0.05) after controlling for ovulation, smoking, and alcohol intake with multivariable regression analysis. There were no significant differences in testosterone or in percentage free estradiol levels between vegetarians and nonvegetarians. Smoking was significantly associated with follicular and luteal DHS and with percentage free follicular estradiol, while alcohol use was significantly and inversely associated with percentage free follicular estradiol after controlling for other variables. The implications for breast cancer risk are discussed.

A new technique for reversible permeabilization of live cells for intracellular delivery of quantum dots

NASA Astrophysics Data System (ADS)

Medepalli, Krishnakiran; Alphenaar, Bruce W.; Keynton, Robert S.; Sethu, Palaniappan

2013-05-01

A major challenge with the use of quantum dots (QDs) for cellular imaging and biomolecular delivery is the attainment of QDs freely dispersed inside the cells. Conventional methods such as endocytosis, lipids based delivery and electroporation are associated with delivery of QDs in vesicles and/or as aggregates that are not monodispersed. In this study, we demonstrate a new technique for reversible permeabilization of cells to enable the introduction of freely dispersed QDs within the cytoplasm. Our approach combines osmosis driven fluid transport into cells achieved by creating a hypotonic environment and reversible permeabilization using low concentrations of cell permeabilization agents like Saponin. Our results confirm that highly efficient endocytosis-free intracellular delivery of QDs can be accomplished using this method. The best results were obtained when the cells were treated with 50 μg ml-1 Saponin in a hypotonic buffer at a 3:2 physiological buffer:DI water ratio for 5 min at 4 ° C.

Influence of gastrointestinal digestion and edible plant combination on oral bioavailability of triterpene saponins, using a biomimetic digestion and absorption system and determination by HPLC.

PubMed

Li, Shun-Xing; Mu, Yang; Zheng, Feng-Ying

2013-11-06

Saponins have many biological activities, but their overload could cause toxicity to the human body. Bionic gastrointestinal digestion and monolayer liposome extraction were used for oral bioavailability assessment of triterpene saponins (notoginsenoside R1, ginsenosides Rb1 and Rd1) in an edible herb (San-Chi) and its compound herbal medicine (Pien Tze Huang, PZH). The concentrations of affinity-monolayer liposome saponins in the chyme were determined by HPLC and used for oral bioavailability assessment. With the digestion of San-Chi and PZH from the stomach to the intestine, the release of saponins in their chyme was increased. The intestinal absorption ratios of N-R1, G-Rb1, G-Rd1, and total saponins from San-Chi were 86.57, 18.56, 73.30, and 40.20%, respectively, which were more than those from PZH (i.e., 19.56, 10.11, 30.11, and 16.08%). The oral bioavailability of saponins was controlled by saponin species, gastrointestinal digestion, and edible plants combination.

Effect of tea saponin on ephyrae and polyps of the moon jellyfish Aurelia sp.1.

PubMed

Dong, Zhijun; Sun, Tingting; Liang, Likun; Wang, Lei

2017-01-01

The moon jellyfish (Aurelia sp.1) is thought to be a nuisance for the sea cucumber aquaculture, which commonly occur in the sea cucumber (Apostichopus japonicus) culture ponds of the Yellow Sea, China. To develop an appropriate method to control Aurelia sp.1 blooms, the toxic effects of tea saponin on Aurelia sp.1 ephyrae and polyps were tested in laboratory experiments. Our results revealed that tea saponin caused significant morphological changes, behavioral abnormality and mortality in Aurelia sp.1 ephyrae and polyps in 24 h and 48 h exposure experiments. The 24 h and 48 h median lethal concentrations (LC50) values of tea saponin for Aurelia sp.1 ephyrae were 1.9 and 1.1 mg L-1 respectively, while the LC50 value for Aurelia sp.1 polyps was 0.4 mg L-1 after 24h and 48 h of exposure to tea saponin. Comparison with literature results of tea saponin on A. japonicus indicates that the resistance of A. japonicus to tea saponin is 12-18 times greater than that of Aurelia sp.1 ephyrae. Therefore, the appropriate tea saponin dosage for the control of Aurelia sp.1 should be paid enough attention in order to minimize possible damage for sea cucumber. We suggest that the recommended level of tea saponin to eradicate Aurelia sp.1 ephyrae and polyps in sea cucumber culture ponds be lower than 1.35 mg L-1.

Effect of tea saponin on ephyrae and polyps of the moon jellyfish Aurelia sp.1

PubMed Central

Sun, Tingting; Liang, Likun; Wang, Lei

2017-01-01

The moon jellyfish (Aurelia sp.1) is thought to be a nuisance for the sea cucumber aquaculture, which commonly occur in the sea cucumber (Apostichopus japonicus) culture ponds of the Yellow Sea, China. To develop an appropriate method to control Aurelia sp.1 blooms, the toxic effects of tea saponin on Aurelia sp.1 ephyrae and polyps were tested in laboratory experiments. Our results revealed that tea saponin caused significant morphological changes, behavioral abnormality and mortality in Aurelia sp.1 ephyrae and polyps in 24 h and 48 h exposure experiments. The 24 h and 48 h median lethal concentrations (LC50) values of tea saponin for Aurelia sp.1 ephyrae were 1.9 and 1.1 mg L-1 respectively, while the LC50 value for Aurelia sp.1 polyps was 0.4 mg L-1 after 24h and 48 h of exposure to tea saponin. Comparison with literature results of tea saponin on A. japonicus indicates that the resistance of A. japonicus to tea saponin is 12–18 times greater than that of Aurelia sp.1 ephyrae. Therefore, the appropriate tea saponin dosage for the control of Aurelia sp.1 should be paid enough attention in order to minimize possible damage for sea cucumber. We suggest that the recommended level of tea saponin to eradicate Aurelia sp.1 ephyrae and polyps in sea cucumber culture ponds be lower than 1.35 mg L-1. PMID:28777817

Effects of Saponins against Clinical E. coli Strains and Eukaryotic Cell Line

PubMed Central

Arabski, Michał; Węgierek-Ciuk, Aneta; Czerwonka, Grzegorz; Lankoff, Anna; Kaca, Wiesław

2012-01-01

Saponins are detergent-like substances showing antibacterial as well as anticancer potential. In this study, the effects of saponins from Quillaja saponaria were analyzed against prokaryotic and eukaryotic cells. Multidrug-resistant clinical E. coli strains were isolated from human urine. As eukaryotic cells, the CHO-K1 cell lines were applied. Antibacterial effect of ampicillin, streptomycin, and ciprofloxacin in the presence of saponins was measured by cultivation methods. Properties of saponins against CHO-K1 cells were measured by the MTT test, hemolysis assay and flow cytometry. Saponin from Quillaja saponaria has a cytotoxic effect at concentrations higher than 25 μg/mL and in the range of 12–50 μg/mL significantly increases the level of early apoptotic cells. Saponin at dose of 12 μg/mL enhances the six E. coli strains growth. We postulate that saponins increase the influx of nutrients from the medium into E. coli cells. Saponins do not have synergetic effects on antibacterial action of tested antibiotics. In contrary, in the presence of saponins and antibiotics, more CFU/mL E. coli cells were observed. This effect was similar to saponins action alone towards E. coli cells. In conclusion, saponins was cytotoxic against CHO-K1 cells, whereas against E. coli cells this effect was not observed. PMID:22500084

Interaction between tolbutamide and ketoconazole in healthy subjects.

PubMed Central

Krishnaiah, Y S; Satyanarayana, S; Visweswaram, D

1994-01-01

A possible interaction between tolbutamide and ketoconazole was studied in seven healthy volunteers. Treatment for 1 week with 200 mg oral ketoconazole increased the elimination half-life (from mean +/- s.d. 3.7 +/- 0.4 to 12.3 +/- 1.9 h) and AUC(0.12 h) of tolbutamide (from 309 +/- 27 to 546 +/- 20 micrograms ml-1 h) by 25 +/- 64 and 66 +/- 15%, respectively. The percentage blood glucose reduction was also increased when tolbutamide and ketoconazole were coadministered. PMID:8186066

Phytochemical characteristic and uterotonic effect of aqueous extract of Ficus deltoidea leaves in rats uterus.

PubMed

Amiera, Z Umi Romaizatul; Nihayah, M; Wahida, I Farah; Rajab, N F

2014-09-01

Ficus deltoidea is traditionally consumed by Malay woman to augment labour and hastening parturition. This study was to investigate the phytochemical present and uterotonic activity of F. deltoidea var. Deltoidea (FDD) and F. deltoidea var. Angustifolia (FDA) leaves aqueous extract. FDD and FDA were qualitatively analysed. In uterine contraction activity, adult female Sprague Dawley rats were pretreated with 0.2 mg kg(-1) diethylstilbestrol 24 h to induce oestrus phase. The rats then killed and uterine horns were taken out, cut into two centimetres length and put into organ bath that connected to Powerlab instrument. The uterus separately tested with cumulative concentrations of FDD (10-1280 μg mL(-1)), FDA (10-1280 μg mL(-1)), oxytocin (0.02-0.64 μg mL(-1)) and combination of oxytocin (0.08 μg mL(-1)) with FDD and FDA (10-1280 μg mL(-1)). FDD showed presence of flavonoid, saponin and tannin meanwhile FDA consist of flavonoid, tannin and terpenoid. Result showed FDD, FDA and oxytocin induced a dose-related increase in force of contraction of isolated rat uterus. The maximum uterine contraction (Emax) produced by FDD, FDA and oxytocin were at the concentration 640 μg mL(-1) (EC50, 5.903 ± 0.529 μg mL), 20 μg mL(-1) (EC50, 290.5 ± 0.158 μg mL(-1)) and 0.4 μg mL(-1) (EC50, 0.060 ± 0.011 μg mL(-1)) respectively. Combination effects of oxytocin with FDD and FDA produced Emax at the concentration 80 μg mL(-1) (EC50, 270.3 ± 0.643 μg mL(-1)) and 1280 μg mL(-1) (EC50, 26.83 ± 0.727 μg mL(-1)), respectively. Study indicated F. deltoidea possess contractile effect on uterine contraction. This plant has great potential to develop as natural uterotonic agent in inducing labour and treatment for post-partum haemorrhage.

In-vitro and in-vivo anti-Trichophyton activity of essential oils by vapour contact.

PubMed

Inouye, S; Uchida, K; Yamaguchi, H

2001-05-01

The minimum inhibitory doses (MIDs) of essential oils by vapour contact to inhibit the growth of Trichophyton mentagrophytes and Trichophyton rubrum on agar medium were determined using airtight boxes. Among seven essential oils examined, cinnamon bark oil showed the least MID, followed by lemongrass, thyme and perilla oils. Lavender and tea tree oils showed moderate MID, and citron oil showed the highest MID, being 320 times higher than that of cinnamon bark oil. The MID values were less than the minimum inhibitory concentration (MIC) values determined by agar dilution assay. Furthermore, the minimum agar concentration (MAC) of essential oils absorbed from vapour was determined at the time of MID determination as the second antifungal measure. The MAC value by vapour contact was 1.4 to 4.7 times less than the MAC remaining in the agar at the time of MIC determination by agar dilution assay. Using selected essential oils, the anti-Trichophyton activity by vapour contact was examined in more detail. Lemongrass, thyme and perilla oils killed the conidia, inhibited germination and hyphal elongation at 1-4 micrograms ml-1 air, whereas lavender oil was effective at 40-160 micrograms ml-1 air. The in-vivo efficacy of thyme and perilla oils by vapour contact was shown against an experimental tinea pedis in guinea pigs infected with T. mentagrophytes. These results indicated potent anti-Trichophyton action of essential oils by vapour contact.

Incorporation of nisin into a meat binding system to inhibit bacteria on beef surfaces.

PubMed

Cutter, C N; Siragusa, G R

1998-07-01

In two separate experiments, the bacteriocin, nisin, was incorporated into a commercially available meat binding system (Fibrimex) and applied to meat surfaces as a way of inhibiting the meat spoilage organism, Brochothrix thermosphacta during extended refrigerated storage. In experiment 1, pre-rigor lean beef carcass tissue (BCT) was inoculated with B. thermosphacta, left untreated (U), treated with 10 micrograms ml-1 nisin (N), Fibrimex (F) or Fibrimex containing 10 micrograms ml-1 nisin (FN), held aerobically at 4 degrees C for up to 7 d, and populations of B. thermosphacta and nisin activity determined. Experiment 2 determined the effects of the same treatments but on post-rigor, frozen and thawed lean BCT that was inoculated, vacuum-packaged, and stored at 4 degrees C for up to 14 d. In both experiments, N- and FN-treated tissues exhibited significantly lower populations of B. thermosphacta compared to U- and F-treated tissues, for the duration of refrigerated storage. Nisin activity was detected up to 7 d in N- and FN-treated samples from experiment 1. However, activity was detected only to days 0 and 2 in FN- and N-treated samples, respectively, from experiment 2. These studies indicate that the addition of a bacteriocin to a meat binding system and application to meat surfaces may be useful in reducing undesirable bacteria in restructured meat products.

Albiziahexoside: a potential source of bioactive saponin from the leaves of Albizzia lebbeck.

PubMed

Ueda, Minoru; Tokunaga, Takashi; Okazaki, Masayuki; Sata, Noriko U; Ueda, Katsuhiro; Yamamura, Shosuke

2003-10-01

Albiziahexoside (1), a new hexaglycosylated saponin, was isolated from leaves of Albizzia lebbeck. Saponin 1, which is an analog of cytotoxic albiziatrioside A (2), did not show cytotoxicity. However, 1 is a potential source of 2 and related bioactive saponins for medicinal use because leaves, which can be regenerated after collection, contain 1 in substantial quantity.

Determination of Four Major Saponins in Skin and Endosperm of Seeds of Horse Chestnut (Aesculus Hippocastanum L.) Using High Performance Liquid Chromatography with Positive Confirmation by Thin Layer Chromatography

PubMed Central

Abudayeh, Zead Helmi Mahmoud; Al Azzam, Khaldun Mohammad; Naddaf, Ahmad; Karpiuk, Uliana Vladimirovna; Kislichenko, Viktoria Sergeevna

2015-01-01

Purpose: To separate and quantify four major saponins in the extracts of the skin and the endosperm of seeds of horse chestnut (Aesculus hippocastanum L.) using ultrasonic solvent extraction followed by a high performance liquid chromatography-diode array detector (HPLC-DAD) with positive confirmation by thin layer chromatography (TLC). Methods: The saponins: escin Ia, escin Ib, isoescin Ia and isoescin Ib were extracted using ultrasonic extraction method. The optimized extraction conditions were: 70% methanol as extraction solvent, 80 °C as extraction temperature, and the extraction time was achieved in 4 hours. The HPLC conditions used: Zorbax SB-ODS-(150 mm × 2.1 mm, 3 μm) column, acetonitrile and 0.10% phosphoric acid solution (39:61 v/v) as mobile phase, flow rate was 0.5 mL min−1 at 210 nm and 230 nm detection. The injection volume was 10 μL, and the separation was carried out isothermally at 30 °C in a heated chamber. Results: The results indicated that the developed HPLC method is simple, sensitive and reliable. Moreover, the content of escins in seeds decreased by more than 30% in endosperm and by more than 40% in skin upon storage for two years. Conclusion: This assay can be readily utilized as a quality control method for horse chestnut and other related medicinal plants. PMID:26819933

Contents of lecithin and choline in crude drugs.

PubMed

Yamasaki, K; Kikuoka, M; Nishi, H; Kokusenya, Y; Miyamoto, T; Matsuo, M; Sato, T

1994-01-01

The determination of lecithin and choline in crude drugs was established by a combination of high performance liquid chromatography (HPLC) with electrochemical detector (ECD) and enzyme reaction. Lecithin in crude drugs extracted with a mixture of chloroform-methanol (2:1) at room temperature was hydrolyzed by phospholipase D. The hydrolyzate was injected to HPLC, and choline was separated from impurities by reverse phase column. The choline was converted to betaine and hydrogen peroxide by passing through column packed with immobilized choline oxidase. This hydrogen peroxide was detected by ECD. The peak area of hydrogen peroxide derived from lecithin was proportional to the concentration of lecithin from 0.10 to 1.52 microgram/ml. Choline in crude drugs was extracted with ethanol under reflux and determined under the same HPLC conditions as lecithin. The peak area of hydrogen peroxide derived from choline was proportional to the concentration of choline from 0.01 to 0.45 microgram/ml. The contents of lecithin and choline in 31 kinds of crude drugs were determined by these established methods. The results showed that Cervi Parvum Cornu, Kokurozin, Foenigraeci Semen and Psoraleae Semen contained more lecithin than other crude drugs, while Angelicae Radix, Foenigraeci Semen, Psoraleae Semen, and especially Hippocampus were found to contain more choline than other crude drugs.

Antimicrobial steroidal saponin and oleanane-type triterpenoid saponins from Paullinia pinnata.

PubMed

Lunga, Paul K; Qin, Xu-Jie; Yang, Xing W; Kuiate, Jules-Roger; Du, Zhi Z; Gatsing, Donatien

2014-10-02

Paullinia pinnata L. (Sapindaceae) is an African woody vine, which is widely used in traditional medicine for the treatment of human malaria, erectile dysfunction and bacterial infections. A phytochemical investigation of its methanol leaf and stem extracts led to the isolation of seven compounds which were evaluated for their antimicrobial properties. The extracts were fractionated and compounds were isolated by chromatographic methods. Their structures were elucidated from their spectroscopic data in conjunction with those reported in literature. The antimicrobial activities of the crude extracts, fractions and compounds were evaluated against bacteria, yeasts and dermatophytes using the broth micro-dilution technique. Seven compounds: 2-O-methyl-L-chiro-inositol (1), β-sitosterol (2), friedelin (3), 3β-(β-D-Glucopyranosyloxy) stigmast-5-ene (4), (3β)-3-O-(2'-Acetamido-2'-deoxy-β-D-glucopyranosyl) oleanolic acid (5), (3β,16α-hydroxy)-3-O-(2'-Acetamido-2'-deoxy-β-D-glucopyranosyl) echinocystic acid (6) and (3β)-3-O-[β-D-glucopyranosyl-(1″-3')-2'-acetamido-2'-deoxy-β-D-galactopyranosyl]oleanolic acid (7) were isolated. Compounds 5 and 7 showed the best antibacterial and anti-yeast activities respectively (MIC value range of 0.78-6.25 and 1.56-6.25 μg/ml), while 6 exhibited the best anti-dermatophytic activity (MIC value range of 6.25-25 μg/ml). The results of the present findings could be considered interesting, taking into account the global disease burden of these susceptible microorganisms, in conjunction with the search for alternative and complementary medicines.

Microwave-assisted extraction (MAE) of bioactive saponin from mahogany seed (Swietenia mahogany Jacq)

NASA Astrophysics Data System (ADS)

Waziiroh, E.; Harijono; Kamilia, K.

2018-03-01

Mahogany is frequently used for medicines for cancer, tumor, and diabetes, as it contains saponin and flavonoid. Saponin is a complex glycosydic compound consisted of triterpenoids or steroids. Saponin can be extracted from a plant by using a solvent extraction. Microwave Assisted Extraction (MAE) is a non-conventional extraction method that use micro waves in the process. This research was conducted by a Complete Random Design with two factors which were extraction time (120, 150, and 180 seconds) and solvent ratio (10:1, 15:1, and 20:1 v/w). The best treatment of MAE were the solvent ratio 15:1 (v/w) for 180 seconds. The best treatment resulting crude saponin extract yield of 41.46%, containing 11.53% total saponins, and 49.17% of antioxidant activity. Meanwhile, the treatment of maceration method were the solvent ratio 20:1 (v/w) for 48 hours resulting 39.86% yield of saponin crude extract, 9.26% total saponins and 56.23% of antioxidant activity. The results showed MAE was more efficient (less time of extraction and solvent amount) than maceration method.

[Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil].

PubMed

Nishimura, M; Kumamoto, Y; Hirose, T; Hayashi, K; Tsukamoto, T; Gohro, T; Ikegaki, S; Kamito, H; Inoke, T; Henmi, I

1990-07-01

We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

[Comparison of blood pressure profiles with flunitrazepam/fentanyl/nitrous oxide vs cervical epidural anesthesia in surgery of the carotid artery].

PubMed

Pluskwa, F; Bonnet, F; Abhay, K; Touboul, C; Rey, B; Marcandoro, J; Becquemin, J B

1989-01-01

A study was carried out to compare the evolution of arterial blood pressure during carotid endarterectomy performed under either general anaesthesia (GA) or cervical epidural anaesthesia (CEA). 20 patients were randomly assigned to two equal groups. In the CEA group, 15 ml of 0.375% bupivacaine and 150 micrograms fentanyl were injected into the epidural space at C7-D1 level. In the GA group, patients were anaesthetized with 0.2 mg.kg-1 flunitrazepam and 5 micrograms.kg-1 fentanyl; intubation was carried out using 0.08 mg.kg-1 vecuronium, and the patients were ventilated with a mixture of nitrous oxide and oxygen (50% of each). Further injections, every 30 min, of 2 micrograms.kg-1 fentanyl were given to the patients in group GA. Blood pressure was monitored continuously, up to 4 h postoperatively, with a radial arterial catheter. Per- or postoperative hypertension was defined as a rise in systolic arterial blood pressure (Pasys) over 180 mmHg for greater than 3 min; this was treated with 20 mg nifedipine intranasally (group CEA) or 100 micrograms fentanyl with 0.5 mg flunitrazepam with or without nifedipine (group GA). Per- or postoperative hypotension was defined as a fall in Pasys below 100 mmHg and or a 30% fall in mean arterial blood pressure for greater than 3 min; this was treated, in both groups, with an intravenous bolus of 3 mg ephedrine. Patients in group CEA experienced more frequent episodes of peroperative hypertension (8/2; p less than 0.02) and postoperative hypotension (5/1) than group GA.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrolysis of an orally active platelet inhibitory prostanoid amide in the plasma of several species.

PubMed

Honohan, T; Fitzpatrick, F A; Booth, D G; McGrath, J P; Morton, D R; Nishizawa, E

1980-01-01

The prostanoid 3-oxa-4,5,6-trinor-3,7-inter-m-phenylene-PGE1-amide (OI-PGE1-amide) has a prolonged duration of oral platelet aggregation inhibitory activity when compared to the parent free acid (OI-PGE1) in the rat. When incubated in rat plasma at 1 microgram/ml for 30 seconds prior to addition of ADP, OI-PGE1-amide inhibits in vitro rat platelet aggregation approximately 50%. OI-PGE1 inhibits at 1 ng/ml. Inhibition of platelet aggregation by plasma incubated with OI-PGE1-amide (1 microgram/ml) increases with time and the rate of this increase differs with species. Incubation of OI-PGE1 in plasma does not result in an increase of platelet inhibitory activity with time. The increase of platelet inhibitory activity was assumed to indicate hydrolysis of OI-PGE1-amide to the more active OI-PGE1. A compound, different from OI-PGE1-amide, was isolated by an ion exchange/silica gel separation sequence from an incubation of OI-PGE1-amide in rat plasma. It had potent platelet aggregation inhibitory activity. This material was shown to be OI-PGE1 by thin-layer chromatography, gas chromatography and mass spectral analysis. Studies with [3H]-OI-PGE1-amide confirmed the formation of OI-PGE1 in plasma incubations. Amide hydrolytic activity was significantly different between species, the rank order being: rat greater than guine pig greater than monkey = human greater than dog. This relationship corresponded with that determined by measuring the increase in platelet inhibitory activity with time in plasma incubations of OI-PGE1-amide reported above. Present data indicate that (a) OI-PGE1-amide is hydrolyzed to the parent acid by plasma enzymes of several species and (b) hydrolytic activity of plasma varies widely between species.

[Expression of saponin biosynthesis related genes in different tissues of Panax quinquefolius].

PubMed

Wang, Kang-Yu; Liu, Wei-Can; Zhang, Mei-Ping; Zhao, Ming-Zhu; Wang, Yan-Fang; Li, Li; Sun, Chun-Yu; Hu, Ke-Xin; Cong, Yue-Yi; Wang, Yi

2018-01-01

The relationship between saponin content of Panax quinquefolius in different parts of the organization and expression of ginsenoside biosynthesis related gene was obtained by the correlation analysis between saponin content and gene expression. The 14 tissue parts of P. quinquefolius were studied, six saponins in P. quinquefolius. Samples (ginsenoside Rg₁, Re, Rb₁, Rc, Rb₂ and Rd), group saponins and total saponins were determined by high performance liquid chromatography and vanillin-sulfuric acid colorimetric method. Simultaneously, the expression levels of 7 ginsenoside biosynthesis related genes ( SQS, OSC, DS, β-AS, SQE, P450 and FPS ) in different tissues of P. quinquefolius were determined by Real-time fluorescence quantitative PCR. Although 7 kinds of ginsenoside biosynthesis related enzyme gene in the P. quinquefolius involved in ginsenoside synthesis, the expression of β-AS and P450 genes had no significant effect on the content of monosodium saponins, grouping saponins and total saponins, FPS, SQS, OSC, DS and SQE had significant or extremely significant on the contents of single saponins Re, Rg1, Rb1, Rd, group saponin PPD and PPT, total saponin TMS and total saponin TS ( P <0.05 or P <0.01). The biosynthesis of partial saponins, grouping saponins and total saponins in P. quinquefolius was affected by the interaction of multiple enzyme genes in the saponin synthesis pathway, the content of saponins in different tissues of P. quinquefolius was determined by the differences in the expression of key enzymes in the biosynthetic pathway. Therefore, this study further clarified that FPS, SQS, OSC, DS and SQE was the key enzyme to control the synthesis of saponins in P. quinquefolius by correlation analysis, the biosynthesis of ginsenosides in P. quinquefolius was regulated by these five kind of enzymes in cluster co-expression of interaction mode. Copyright© by the Chinese Pharmaceutical Association.

Longitudinal changes in blood lead level in children and their relationship to season, age, and exposure to paint or plaster.

PubMed Central

McCusker, J

1979-01-01

Children screened for lead poisoning in the Brownsville district of New York City in either summer or winter were followed with blood lead tests for approximately six months to one year from screening to measure longitudinal changes in blood lead level and to identify some determinants of the changes. Only minimal evidence was found of the hypothesized summer rise in blood lead level, while the predominant trend seemed to be for blood lead levels to display statistical regression to the mean. In children found to have low to intermediate blood lead levels (less than 55 microgram/100ml) at screening, variables which were found to predict a rise in blood lead level of 10 microgram/100ml or greater from winter to summer were under age three and/or exposure to paint or plaster. PMID:426160

[Study on the inhibitory activity, in vitro, of baicalein and baicalin against skin fungi and bacteria].

PubMed

Yang, D; Hu, H; Huang, S; Chaumont, J P; Millet, J

2000-05-01

In this paper, we concentrated in examining, in vitro, the antiseptic activity of the baicalein and baicalin upon the seventeen pathogenic skin fungal and sixteen skin bacterial strains, these two flavonic compounds were known principally as the biosubstances of a traditional Chinese medicinal plant: Scutellaria baicalensis. In agar media, the baicalein possessed potent specific activity against the pathogenic yeasts with MICs of 70-100 micrograms/ml; But in the same condition, no inhibitory effect was observed upon dermatophytes and filamentous imperfect fungi for baicalein, and upon all used strains for baicalin. According to the antibacterial test of baicalein, a high efficacy was achieved against certain causative specie of axillary and foot's odour such as Micrococcus sedentarius, Staphylococcus epidermidis, S. hominis and C. xerosis with a MICs inferior to 250 micrograms/ml. The good inhibitory activity of baicalein could be linked to the group hydroxyl (-OH) in position seven of the molecule.

Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin.

PubMed

Mecklenburg, M; Lindbladh, C; Li, H; Mosbach, K; Danielsson, B

1993-08-01

A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay-based biosensors. The implications of these results upon on-line analysis are discussed.

Ecology and thermal inactivation of microbes in and on interplanetary space vehicle components

NASA Technical Reports Server (NTRS)

Campbell, J. E.

1971-01-01

Data showing that 90 C was a more effective temperature than 125 C for the destruction of Bacillus subtilis var. niger when the head-space moisture was fixed at 474 micrograms H2O/ml have been confirmed and are summarized. The influence of head-space moisture at 90 C was investigated and it was observed that as the head-space moisture was increased 474 micrograms H2O/ml, there was a corresponding increase in lethality of the system. This moisture level corresponded to 100% relative humidity at 90 C, and additional water in the cans should have had no effect. A profound descrease was observed in the destruction of the organisms when additional water was added. The discontinuity observed in these data is troublesome and must be resolved as the first step in an orderly exploration of low temperature inactivation of B. subtilis var. niger.

High-performance liquid chromatographic determination of loxoprofen and its diastereomeric alcohol metabolites in biological fluids by fluorescence labelling with 4-bromomethyl-6,7-methylenedioxycoumarin.

PubMed

Naganuma, H; Kawahara, Y

1990-09-14

A simple and sensitive high-performance liquid chromatographic procedure to determine loxoprofen and its diastereomeric alcohol metabolites in biological specimens is described. The analysis involves liquid-liquid extraction with benzene, pre-column derivatization with a highly fluorogenic reagent, 4-bromomethyl-6,7-methylenedioxycoumarin (BrMDC) and subsequent separation on a reversed-phase column. Loxoprofen, its pharmacologically active metabolite, trans-alcohol, and less active cis-alcohol were completely separated within 20 min with a mobile phase of 55% of aqueous acetonitrile containing acetic acid. Any endogenous substances do not interfere in the analysis of either plasma or urine samples. The quantitation limit was 0.01 micrograms/ml for human plasma and 0.05 micrograms/ml for urine. The method was applied to a pharmacokinetic study in healthy human subjects who had received 60 mg of loxoprofen sodium.

Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs.

PubMed Central

Saito, A; Sawatari, K; Fukuda, Y; Nagasawa, M; Koga, H; Tomonaga, A; Nakazato, H; Fujita, K; Shigeno, Y; Suzuyama, Y

1985-01-01

The antimicrobial activity of ofloxacin was tested against 15 standard strains and 37 clinical and environmental strains of Legionella pneumophila by agar dilution susceptibility studies with a new growth medium. The ofloxacin MICs were inoculum dependent and ranged from 0.03 to 0.125 microgram/ml. The antibacterial activities of other agents tested relative to ofloxacin were rifampin greater than ofloxacin greater than josamycin greater than pipemidic acid. Ofloxacin, at concentrations equal to or greater than 0.05 microgram/ml, inhibited the growth of L. pneumophila grown in human monocytes. The therapeutic efficacy of ofloxacin in experimental guinea pig L. pneumophila pneumonia was greater than that observed with erythromycin or josamycin therapy; it was less effective than was rifampin. Ofloxacin was very active against intracellular L. pneumophila in these experiments and should be studied in the therapy of human Legionnaires disease. PMID:3862361

Determination of vitamin E in human plasma by high-performance liquid chromatography.

PubMed

Cooper, J D; Thadwal, R; Cooper, M J

1997-03-07

The use of selective protein precipitation to enhance the recovery of vitamin E from plasma, by minimising binding with very-low-density lipoproteins, is reported. The procedure employed treatment of plasma with magnesium chloride and tungstate, followed by methanol protein precipitation. Separation of vitamin E was performed using reversed-phase high-performance liquid chromatography of the methanol extracts with subsequent UV detection of the compound. Using this technique the procedure was observed to be specific for vitamin E and linear over the range 1.0 to 40.0 micrograms/ml. The within-run imprecision (C.V.) at three different supplemented plasma vitamin E concentrations of 5.0, 10.0 and 20.0 micrograms/ml was 4.51, 3.33 and 2.58%, respectively, and the between-run imprecision (C.V.) estimated to be 5.19, 3.69 and 3.67%, respectively. With the same supplemented plasma vitamin E concentrations, the overall accuracy (bias) of the procedure, using an albumin matrix for calibration, was estimated to be 6.0, -5.0 and -3.5%, respectively, and the recovery of vitamin E from six different spiked plasma samples estimated to be 98.2 +/- 2.6%.

Saponins from soy bean and mung bean inhibit the antigen specific activation of helper T cells by blocking cell cycle progression.

PubMed

Lee, Suk Jun; Bae, Joonbeom; Kim, Sunhee; Jeong, Seonah; Choi, Chang-Yong; Choi, Sang-Pil; Kim, Hyun-Sook; Jung, Woon-Won; Imm, Jee-Young; Kim, Sae Hun; Chun, Taehoon

2013-02-01

Treatment of helper T (Th) cells with saponins from soy bean and mung bean prevented their activation by inhibiting cell proliferation and cytokine secretion. However, the saponins did not affect the expression of major histocompatibility complex class II (A(b)) and co-stimulatory molecule (CD86) on professional antigen-presenting cells. Instead, the saponins directly inhibited Th cell proliferation by blocking the G(1) to S phase cell cycle transition. Moreover, blocking of the cell cycle by the saponins was achieved by decreased expression of cyclin D1 and cyclin E, and constitutive expression of p27(KIP1). Saponins also increased stability of p27(KIP1) in Th cells after antigenic stimulation.

Tramadol reduces the sweating, vasoconstriction, and shivering thresholds.

PubMed

De Witte, J L; Kim, J S; Sessler, D I; Bastanmehr, H; Bjorksten, A R

1998-07-01

The analgesic tramadol inhibits the neuronal reuptake of norepinephrine and 5-hydroxytryptamine, facilitates 5-hydroxytryptamine release, and activates mu-opioid receptors. Each of these actions is likely to influence thermoregulatory control. We therefore tested the hypothesis that tramadol inhibits thermoregulatory control. Eight volunteers were evaluated on four study days, on which they received no drugs, tramadol 125 mg, tramadol 250 mg, and tramadol 250 mg with naloxone, respectively. Skin and core temperatures were gradually increased until sweating was observed and then decreased until vasoconstriction and shivering were detected. The core temperature triggering each response defined its threshold. Tramadol decreased the sweating threshold by -1.03 +/- 0.67 degrees C microgram-1.mL (r2 = 0.90 +/- 0.12). Tramadol also decreased the vasoconstriction threshold by -3.0 +/- 4.0 degrees C microgram-1.mL (r2 = 0.94 +/- 0.98) and the shivering threshold by -4.2 +/- 4.0 degrees C microgram-1.mL(r2 = 0.98 +/- 0.98). The sweating to vasoconstriction interthreshold range nearly doubled from 0.3 +/- 0.4 degree C to 0.7 +/- 0.6 degree C during the administration of large-dose tramadol (P = 0.04). The addition of naloxone only partially reversed the thermoregulatory effects of tramadol. The thermoregulatory effects of tramadol thus most resemble those of midazolam, another drug that slightly decreases the thresholds triggering all three major autonomic thermoregulatory defenses. In this respect, both drugs reduce the "setpoint" rather than produce a generalized impairment of thermoregulatory control. Nonetheless, tramadol nearly doubled the interthreshold range at a concentration near 200 ng/mL. This indicates that tramadol slightly decreases the precision of thermoregulatory control in addition to reducing the setpoint. The authors evaluated the effects of the analgesic tramadol on the three major thermoregulatory responses: sweating, vasoconstriction, and shivering. Tramadol had only slight thermoregulatory effects. Its use is thus unlikely to provoke hypothermia or to facilitate fever.

Effect of saponins on n-hexane removal in biotrickling filters.

PubMed

Tu, Yanhong; Yang, Chunping; Cheng, Yan; Zeng, Guangming; Lu, Li; Wang, Lu

2015-01-01

Saponins was applied to enhance the removal of n-hexane in a biotrickling filter (BTF) in this study. Comparison experiments were carried out to examine the effect of saponins on n-hexane removal in two BTFs at various saponins concentrations, n-hexane loading rates (LRs) and gas empty bed contact times (EBCTs). Results show that the optimum concentration of saponins in nutrient feed was 50.0mgL(-1). When organic LR of n-hexane increased from 47.8 to 120.0gm(-3)h(-1), the removal efficiency (RE) for BTF1 (with saponins) and BTF2 (without saponins) decreased from 91.3% to 83.3% and from 62.8% to 56.8%, respectively. As gas EBCT decreased from 30.0 to 7.5s, the RE declined from 88.4% to 64.5% for BTF1 and from 61.4% to 38.3% for BTF2. Saponins could also decrease the biomass accumulation rate within the medium bed. These results could be referred in the design and operation of BTFs for hydrophobic VOC removal. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of histamine and eicosanoid release from dispersed human lung cells in vitro by quinotolast.

PubMed

Okayama, Y; Hiroi, J; Lau, L C; Church, M K

1995-12-01

We have examined the effects of a new anti-allergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) yetrazolate monohydrate], in inhibiting the release of histamine and the generation of leukotriene (LT) C4 and prostaglandin (PG) D2 from dispersed human lung cells and compared this with those of its active metabolite in the rat, hydroxy quinotolast, and reference drugs, tranilast and sodium cromoglycate (SCG). Quinotolast in the concentration range of 1-100 micrograms/ml inhibited histamine and LTC4 release in a concentration-dependent manner. The inhibitory effect of quinotolast on histamine release from dispersed lung cells was largely independent of the preincubation period, no tachyphylaxis being observed. Hydroxy quinotolast and tranilast showed a weak inhibition of histamine release only when the drugs were added to the cells simultaneously with anti-IgE challenge. Quinotolast, 100 micrograms/ml, and SCG, 1 mM, significantly inhibited PGD2 and LTC4 release. Quinotolast inhibited PGD2 release by 100% and LTC4 release by 54%, whereas SCG inhibited PDG2 release by 33% and LTC4 release by 100%. No cross-tachyphylaxis between quinotolast and SCG was observed. The results demonstrated that quinotolast showed a significant inhibition of inflammatory mediators from human dispersed lung cells, suggesting that quinotolast is a good candidate for a clinical anti-allergic drug.

Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo.

PubMed

Pallapies, D; Salinger, A; Meyer zum Gottesberge, A; Atkins, D J; Rohleder, G; Nagyiványi, P; Peskar, B A

1995-01-01

The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg/kg lysine clonixinate or 1 mg/kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg/kg lysine clonixinate and of 0.0225, 0.15 and 1 mg/kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 micrograms/ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 micrograms/ml, respectively).

New Cytotoxic Triterpenoid Saponins from the Roots of Albizia gummifera (J.F.Gmel.) C.A.Sm.

PubMed

Simo, Line Made; Noté, Olivier Placide; Mbing, Joséphine Ngo; Aouazou, Sarah Ali; Guillaume, Dominique; Muller, Christian Dominique; Pegnyemb, Dieudonné Emmanuel; Lobstein, Annelise

2017-10-01

As part of our search for new bioactive saponins from Cameroonian medicinal plants, two new oleanane-type saponins, named gummiferaosides D and E (1 and 2), along with one known saponin, julibroside J 8 (3), were isolated from the roots of Albizia gummifera. Their structures were established on the basis of extensive 1D- and 2D-NMR ( 1 H- and 13 C-NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY, and HMBC) and HR-ESI-MS studies, and by chemical evidence. The apoptotic effect of saponins 1 - 3 was evaluated on the A431 human epidermoid cancer cell. Flow cytometric analyses showed that saponins 1 - 3 induced apoptosis of human epidermoid cancer cell (A431) in a dose-dependent manner. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I.

PubMed

Skottner, A; Clark, R G; Fryklund, L; Robinson, I C

1989-05-01

A new mutant GH-deficient dwarf rat has been used to study the effects of iv infusions of human GH (hGH) and recombinant human insulin-like growth factor I (hIGF-I). This animal has only about 5% of normal pituitary GH content, low circulating GH levels, and no regular GH surges. The defect seems to be specific for GH. Infusions of hIGF-I at 180 micrograms/day for 9 days elevated serum IGF-I concentrations significantly over those in the saline-infused controls (713 +/- 20 ng/ml vs. 395 +/- 31 ng/ml); hGH infusions did not raise IGF-I levels significantly (435 +/- 20 ng/ml). Gel filtration of serum samples showed that the high-dose hIGF-I infusions increased free IGF concentrations, without apparently altering the pattern of IGF-I binding whereas hGH infusions increased the amount of high mol wt IGF-I binding protein. Neither IGF-I nor hGH infusions affected the small amounts of rat GH present in the dwarf rat pituitary glands. Continuous iv infusions of hGH (200 mU/day for 9 days) stimulated body wt gain (2.1 +/- 0.2 g/day) and bone growth (96 +/- 9 microns/day) significantly compared to saline-infused dwarf rats (1.2 +/- 0.3 g/day and 43 +/- 3 microns/day). Infusions of hIGF-I at 180 micrograms/day produced a body wt gain (2.1 +/- 0.5 g/day) similar to that seen in the hGH-infused group but a significantly smaller stimulation of bone growth (63 +/- 3 microns/day). Infusion of a 5-fold lower dose of hIGF-I (36 micrograms/day for 9 days) had no effect on body wt or bone growth. Food intake was unaffected by either hGH or hIGF-I infusions. The pattern of tissue growth was affected differentially by hGH and IGF-I infusions that produced the same overall body wt gain. hGH induced a relatively proportional growth in most of the organs studied, whereas hIGF-I infusion at 180 micrograms/day stimulated a disproportionately greater growth of the kidney, adrenals, and spleen. In some of the animals, tissues were extracted for RIA of IGF-I; the amounts of IGF-I in the liver were similar in control, hGH, or IGF-I-infused animals, whereas kidney and adrenals from IGF-I infused animals contained larger amounts of immunoreactive IGF-I than did those tissues from hGH-treated rats. Thus, both hGH and hIGF-I can promote growth in the mutant dwarf rat, but they differ both quantitatively and qualitatively in their pattern of actions.

New steroidal saponins from the rhizomes of Paris delavayi and their cytotoxicity.

PubMed

Liu, Yang; Tian, Xiangrong; Hua, Dong; Cheng, Guang; Wang, Kaixing; Zhang, Lihan; Tang, Haifeng; Wang, Minchang

2016-06-01

Four new furostanol saponins, named padelaosides C-F (1-4), together with four known spirostanol saponins 5-8 were isolated from the rhizomes of Paris delavayi Franchet. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidences. The discovery of the new compounds 1-4 extended the diversity and complexity of this furostanol saponin family. The cytotoxicity of all the saponins was evaluated for their cytotoxicity against human glioblastoma U87MG and human hepatocellular carcinoma Hep-G2 cell lines. The known spirostanol saponins 7 and 8 exhibited notable cytotoxicity against the two tumor cell lines with IC50 values of 1.13 and 3.42μM, respectively, while the new furostanol saponins 3 and 4 showed moderate cytotoxicity with IC50 values of 15.28 to 16.98μM. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of two different saponins on the organization of model lipid membranes.

PubMed

Korchowiec, Beata; Gorczyca, Marcelina; Wojszko, Kamila; Janikowska, Maria; Henry, Max; Rogalska, Ewa

2015-10-01

Saponins, naturally occurring plant compounds are known for their biological and pharmacological activity. This activity is strongly related to the amphiphilic character of saponins that allows them to aggregate in aqueous solution and interact with membrane components. In this work, Langmuir monolayer techniques combined with polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) and Brewster angle microscopy were used to study the interaction of selected saponins with lipid model membranes. Two structurally different saponins were used: digitonin and a commercial Merck Saponin. Membranes of different composition, namely, cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) were formed at the air/water and air/saponin solution interfaces. The saponin-lipid interaction was characterized by changes in surface pressure, surface potential, surface morphology and PM-IRRAS signal. Both saponins interact with model membranes and change the physical state of membranes by perturbing the lipid acyl chain orientation. The changes in membrane fluidity were more significant upon the interaction with Merck Saponin. A higher affinity of saponins for cholesterol than phosphatidylglycerols was observed. Moreover, our results indicate that digitonin interacts strongly with cholesterol and solubilize the cholesterol monolayer at higher surface pressures. It was shown, that digitonin easily penetrate to the cholesterol monolayer and forms a hydrogen bond with the hydroxyl groups. These findings might be useful in further understanding of the saponin action at the membrane interface and of the mechanism of membrane lysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway.

PubMed

Bhardwaj, Jyoti; Chaudhary, Narendra; Seo, Hyo-Jin; Kim, Min-Yong; Shin, Tai-Sun; Kim, Jong-Deog

2014-06-01

The anti-cancer activity of saponins and phenolic compounds present in green tea was previously reported. However, the immunomodulatory and adjuvanticity activity of tea saponin has never been studied. In this study, we investigated the immunomodulatory effect of tea saponin in T-lymphocytes and EL4 cells via regulation of cytokine response and mitogen-activated protein kinases (MAPK) signaling pathway. Quantitative analysis of mRNA expression level of cytokines were performed by reverse transcription polymerase chain reaction following stimulation with tea saponin, ovalbumin (OVA) alone or tea saponin in combination with OVA. Tea saponin inhibited the proliferation of EL4 cells measured in a dose-dependent manner. No cytotoxicity effect of tea saponin was detected in T-lymphocytes; rather, tea saponin enhanced the proliferation of T-lymphocytes. Tea saponin with OVA increased the expression of interleukin (IL)-1, IL-2, IL-12, interferon-γ and tumor necrosis factor (TNF)-α and decreased the expression level of IL-10 and IL-8 in T-lymphocytes. Furthermore, tea saponin, in the presence of OVA, downregulated the MAPK signaling pathway via inhibition of IL-4, IL-8 and nuclear factor kappaB (NF-κB) in EL4 cells. Th1 cytokines enhancer and Th2 cytokines and NF-κB inhibitor, tea saponin can markedly inhibit the proliferation and invasiveness of T-lymphoma (EL4) cells, possibly due to TNF-α- and NF-κB-mediated regulation of MAPK signaling pathway.

Effects of karaya saponin and Rhodobacter capsulatus on yolk cholesterol in laying hens.

PubMed

Afrose, S; Hossain, M S; Maki, T; Tsujii, H

2010-06-01

1. It has been reported that karaya saponin and Rhodobacter capsulatus individually have hypocholesterolaemic activity in laying hens. This study focuses on the effect of adding karaya saponin with R. capsulatus to hen's diet with regard to serum and egg yolk cholesterol and triglycerides. 2. A total of 56 Boris Brown laying hens were divided into 7 groups at 20 weeks of age. Combinations of 25, 50, 75 mg kg(-1) karaya saponin and R. capsulatus 200 and 400 mg kg(-1) were used as treatment groups. 3. After 8 weeks of supplementation, the effects of all the combinations of karaya saponin and R. capsulatus on serum and egg yolk cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol were greater than either karaya saponin or R. capsulatus alone. The combination of karaya saponin 50 mg kg(-1)+ R. capsulatus 400 mg kg(-1) exhibited the greatest reduction of serum (325%) and yolk (225%) cholesterol and the greatest increase of faecal, liver bile acids and yolk fatty acid (oleic, linoleic and linolenic) concentrations. In addition, egg production and yolk colour were significantly improved by the combined use of karaya saponin and R. capsulatus supplementation. 4. Therefore, the dietary supplementation of karaya saponin and R. capsulatus may lead to the production of a low-cholesterol egg, with production performance maintained at a standard level.

Bronchodilator action of inhaled fenoterol and ipratropium in normal subjects: a teaching exercise for medical students.

PubMed Central

Taylor, R G; Maclagan, J; Cook, D G

1989-01-01

1. A pharmacology practical class for preclinical medical students was designed as a placebo-controlled, double-blind trial of two bronchodilator drugs. 2. Fenoterol hydrobromide (800 micrograms), ipratropium bromide (80 micrograms) and placebo (propellant only) were given by metered dose inhaler to 79 non-asthmatic volunteers. Their effects on FEV1, heart rate and tremor (assessed by the time taken to thread five sewing needles) were compared. 3. Both drugs caused a significant increase in FEV1: the largest group mean increase was 77 ml, recorded 15 min after fenoterol, and 103 ml, recorded 60 min after ipratropium. 4. Fenoterol also caused a mean increase of 8.7 beats min-1 in heart rate, 5 min after inhalation. This effect was still apparent after 60 min. 5. Fenoterol appeared to prolong needle threading time in some individuals. 6. In subjects who inhaled fenoterol, there were no correlations between the increase in FEV1, the increase in heart rate, or the development of tremor. 7. It is concluded that inhaled fenoterol and ipratropium both cause bronchodilation in normal subjects. Systemic absorption of fenoterol is indicated by the rapid increase in heart rate. The bronchodilator effect of ipratropium suggests that resting airway calibre is governed partly by parasympathetic tone in normal subjects. 8. The bronchodilator and systemic effects of these drugs can be used to demonstrate pharmacological, therapeutic and statistical principles to medical students. PMID:2532922

Alum-type adjuvant effect of non-haemolytic saponins purified from Ilex and Passiflora spp.

PubMed

Silveira, F; Rossi, S; Fernández, C; Gosmann, G; Schenkel, E; Ferreira, F

2011-12-01

Five saponins purified from the leaves of three Ilex species (saponins 1 and 2 from I. dumosa; saponin 3 from I. argentina; saponin 4 from I. paraguariensis) and from Passiflora alata (saponin 5) were evaluated for their in vitro haemolytic activity and in vivo immunostimulatory ability in a mouse model using tetanus toxoid (TT) as a model antigen. The assayed saponins showed very weak or no haemolytic activity over the tested concentration range. Mice were immunized twice with TT formulated with pure saponins 1-5, or with a mixture of saponins from Quillaja saponaria, aluminum hydroxide gel or saline, which were used as controls. The elicited humoral response was evaluated by means of the time course of specific serum antibody levels up to day 131 post-priming (total IgG and isotypes); the cellular response was tested through a delayed-type hypersensitivity (DTH) assay. The assayed saponins, in particular saponins 3 and 5, showed an adjuvant effect similar to that of alum for all tested parameters. The immunostimulating potential of these compounds deserves further investigation, especially taking into account that some Ilex spp. and Passiflora alata are native crops of widespread use and economical importance in Latin America. Copyright © 2011 John Wiley & Sons, Ltd.

Mass spectrometry-based phytochemical screening for hypoglycemic activity of Fagioli di Sarconi beans (Phaseolus vulgaris L.).

PubMed

Pascale, Raffaella; Bianco, Giuliana; Cataldi, Tommaso R I; Kopplin, Philippe-Schmitt; Bosco, Federica; Vignola, Lisiana; Uhl, Jenny; Lucio, Marianna; Milella, Luigi

2018-03-01

The present study deals with the evaluation of antidiabetic activities of Fagioli di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the European Union with the mark PGI (i.e., Protected Geographical Indication), and cultivated in Basilicata (southern Italy). For this purpose, α-glucosidase and α-amylase assays were assessed; among all bean ecotypes, the tight green seed colour of Verdolino extracts exhibited the highest α-glucosidase and α-amylase inhibitory activity with IC 50 =1.1±0.1μg/ml and IC 50 =19.3±1.1μg/ml, respectively. Phytochemical compound screening of all Fagioli di Sarconi beans performed by flow injection-electrospray ionization-ultrahigh resolution mass spectrometry (uHRMS) and based on the calculation of elemental formulas from accurate m/z values, was helpful to annotate specific compounds, such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely responsible for their biological activity. Copyright © 2017. Published by Elsevier Ltd.

Tea saponin reduced methanogenesis in vitro but increased methane yield in lactating dairy cows.

PubMed

Guyader, J; Eugène, M; Doreau, M; Morgavi, D P; Gérard, C; Martin, C

2017-03-01

The effect of tea saponin supplementation in the ruminant diet on methane emissions, rumen fermentation, and digestive processes is still under debate. The objective of this study was to assess the effect of this plant extract on methanogenesis, total-tract digestibility, and lactating performances of dairy cows. The work included 2 independent and successive experiments. First, the effect of 7 tea saponin doses (from 0 to 0.50 g/L) on methane emissions and protozoa concentrations was tested in 2 repeated in vitro batch culture incubations using bovine rumen contents as inoculum and a cereal mixture as substrate. After 18 h of incubation, total gas production and composition as well as rumen fermentation parameters and protozoa concentration were analyzed. Increasing dosage of the plant extract reduced methane production and protozoa concentration, with a maximum reduction of 29% for CH 4 (mL/g of substrate) and 51% for protozoa (10 5 /mL). Tea saponin did not affect volatile fatty acids concentration, but marginally decreased total gas production by 5% at the highest dose. Second, a 2-period crossover design experiment was carried out with 8 lactating dairy cows fed a basal diet (54% corn silage, 6% hay, and 40% pelleted concentrates on a dry matter basis) without (control) or with 0.52% tea saponin (TSP). Each experimental period lasted 5 wk. Animals were fed ad libitum during the first 3 wk of the period (wk 1, 2, and 3) and restricted (95% of ad libitum intake) during the last 2 wk (wk 4 and 5). Intake and milk production were recorded daily. Methane emissions were quantified using open chambers (2 d, wk 4). Total-tract digestibility and nitrogen balance were determined from total feces and urine collected separately (5 d, wk 5). Rumen fermentation parameters and protozoa concentration were analyzed from samples taken after morning feeding (1 d, wk 5). Milk production, dry matter intake, and feed efficiency were reduced with TSP (-18, -12, and -8%, respectively). As daily methane production (g/d) was not affected, methane emissions (g/kg of dry matter intake) increased by 14% with TSP. Total-tract digestibility and nitrogen balance were similar between diets, except for acid detergent fiber digestibility, which tended to be improved with TSP (+4 percentage units). Rumen fermentation parameters and protozoa concentration were relatively unchanged by diets. Under the conditions of this experiment, tea saponin is not efficient to reduce methane emissions from dairy cows. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Correlation of gene expression related to amount of ginseng saponin in 15 tissues and 6 kinds of ginseng saponin biosynthesis].

PubMed

Wang, Kang-yu; Zhang, Mei-ping; Li, Chuang; Jiang, Shi-cui; Yin, Rui; Sun, Chun-yu; Wang, Yi

2015-08-01

Fifteen tissues of 4-year-old fruit repining stage Jilin ginseng were chosen as materials, six kinds of monomer saponins (ginsenosides Rg1, Re, Rb1, Rc, Rb2 and Rd) content in 15 tissues was measured by HPLC and vanillin-sulfuric acid method. The relative expression of FPS, SQS, SQE, OSC, β-AS and P450 genes in 15 tissues was analyzed by real-time PCR. The correlations between ginseng saponin content in 15 tissues of Jilin ginseng and biosynthetic pathway -related genes were obtained. The results showed that was a synergistic increase and decrease trend of positive linear correlation among six kinds of monomer saponin content, and there was a significantly (P < 0.01) positive correlation between monomer saponin content and total saponins content. Monomer saponin content and 6 kinds of enzyme gene correlation were different. Biosynthesis of ginseng total saponins and monomer saponin were regulated by six kinds of participation ginsenoside biosynthesis enzyme genes, the expression of these six kinds of genes in different tissues of ginseng showed collaborative increase and decrease trend, and regulated biosynthesis of ginseng ginsenoside by group coordinative manner.

[Contents of total anthocyanins and total saponins as well as composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma].

PubMed

Zhao, Chang-ling; Yang, Sheng-chao; Chen, Zhong-jian; Shen, Yong; Wei, Fu-gang; Wang, Wu; Long, Ting-ju

2014-10-01

The contents of total anthocyanins and total saponins as well as the composition of saponin monomers of Purple and Green Notoginseng Radix et Rhizoma were studied to compare the medicinal quality and commercial values. Three-year-old Notoginseng Radix et Rhizoma was selected as the research materials. The contents of total anthocyanins and total saponins were determined by spectrophotometry. The compositions of saponin monomers were monitored by HPLC. The significance of content differences was determined by variance analysis. The contents of total anthocyanins and total saponins of Purple Notoginseng Radix et Rhizomawere about 204.85% and 33.86% higher than those of Green Notoginseng Radix et Rhizoma respectively. The Purple and Green Notoginseng Radix et Rhizoma both contained five saponin monomers whose contents were as follows: ginsenoside Rg1 > ginsenoside Rb1 > notoginsenoside R1 > ginsenoside Rd > ginsenoside Re. The contents of notoginsenoside R1, ginsenoside Rd and ginsenoside Re of Purple Notoginseng Radix et Rhizoma were about 16.03%, 10.83% and 5.39% higher than those of Green Notoginseng Radix et Rhizoma respectively. However, the contents of ginsenoside Rg1 and ginsenoside Rb1 of Green Notoginseng Radix et Rhizoma were about 0.93% and 3.33% higher than those of Purple Notoginseng Radix et Rhizoma respectively. With respect to Green Notoginseng Radix et Rhizoma, the increase of the total anthocyanins in Purple Notoginseng Radix et Rhizoma reached a significant level, but the increases of total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re and the decreases of ginsenoside Rg1 and ginsenoside Rb1 did not. The total anthocyanins accumulation in Notoginseng Radix et Rhizoma implies the content increases of the total saponins, notoginsenoside R1, ginsenoside Rd and ginsenoside Re, and the slight decreases of ginsenoside Rg1 and ginsenoside Rb1 contents; but the type and relative contents of saponin monomers remain unchanged. The medicinal quality and commercial value of Purple Notoginseng Radix et Rhizoma are higher than those of Green Notoginseng Radix et Rhizoma.

Dianthins, ribosome-damaging proteins with anti-viral properties from Dianthus caryophyllus L. (carnation).

PubMed Central

Stirpe, F; Williams, D G; Onyon, L J; Legg, R F; Stevens, W A

1981-01-01

1. Dianthin 30 and dianthin 32, two proteins isolated from the leaves of Diathus caryophyllus (carnation), were purified to homogeneity by chromatography on CM-cellulose. 2. The mol.wt. of dianthin 30 is 29 500 and that of dianthin 32 is 31 700. Both dianthins are glycoproteins containing mannose. 3. Dianthins inhibit protein synthesis in a lysate of rabbit reticulocytes, with an ID50 (concentration giving 50% inhibition) of 9.15 ng/ml (dianthin 30) and 3.6 ng/ml (dianthin 32). They act by damaging ribosomes in a less-than-equimolar ratio. Protein synthesis by intact cells is partially inhibited by dianthins at a concentration of 100 microgram/ml. 4. Dianthins mixed with tobacco-mosaic virus strongly decrease the number of local lesions on leaves of Nicotiana glutinosa. Images Fig. 2. PMID:7316958

Inhibitory effects of chickpea and Tribulus terrestris on lipase, α-amylase and α-glucosidase.

PubMed

Ercan, Pınar; El, Sedef Nehir

2016-08-15

The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, α-amylase and α-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against α-glucosidase (IC50 6967 ± 343 and 2885 ± 85.4 μg/ml, respectively) and α-amylase (IC50 343 ± 26.2 and 167 ± 6.12 μg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 ± 2.03 and 9.74 ± 1.09 μg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activity of Saponins from Medicago species Against HeLa and MCF-7 Cell Lines and their Capacity to Potentiate Cisplatin Effect.

PubMed

Avato, Pinarosa; Migoni, Danilo; Argentieri, Mariapia; Fanizzi, Francesco P; Tava, Aldo

2017-11-24

Saponins from Medicago species display several biological activities, among them apoptotic effects against plant cells have been evidenced. In contrast, their cytotoxic and antitumor activity against animal cells have not been studied in great details. To explore the cytotoxic properties of saponin from Medicago species against animal cells and their effect in combination with the antitumoral drug cisplatin. Cytotoxic activity of saponin mixtures from M. arabica (tops and roots), M. arborea (tops) and M. sativa (tops, roots and seeds) and related prosapogenins from M. arborea and M. sativa (tops) against HeLa and MCF-7 cell lines is described. In addition, cytotoxicity of soyasaponin I and purified saponins (1-8) of hederagenin, medicagenic and zanhic acid is also presented. Combination experiments with cisplatin have been also conducted. Saponins from M. arabica tops and roots (mainly monodesmosides of hederagenin and bayogenin) were the most effective to reduce proliferation of HeLa and MCF-7 cell lines. Among the purified saponins, the most cytotoxic was saponin 1, 3-O-ß-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl hederagenin. When saponins, derived prosapogenins and pure saponins were used in combination with cisplatin, they all, to different extent, were able to potentiate cisplatin activity against HeLa cells but not against MCF-7 cell lines. Moreover uptake of cisplatin in these cell lines was significantly reduced. Overall results showed that specific molecular types of saponins (hederagenin glycosides) have potential as anti-cancer agents or as leads for anti-cancer agents. Moreover saponins from Medicago species have evidenced interesting properties to mediate cisplatin effects in tumor cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Preparation of O/W ginseng saponins-based nanoemulsion and its amplified immune response].

PubMed

Cao, Fahao; Ouyang, Wuqing; Wang, Yanping

2010-02-01

To prepare an O/W ginseng saponins-based nanoemulsion and investigate its amplified immune response. The formulation of ginseng saponins-based nanoemulsion was optimized via the range of nanoemulsion zone in phase diagrams and the solubility of ginseng saponins. Its physicochemical properties were investigated, including morphology, particle size distribution, pH, viscosity and stability. Ginseng saponins-based nanoemulsion as adjuvant was co-administrated with a model antigen ovalbumin (OVA) in mice. Two weeks after the boosting, the serum levels of OVA-specific antibody and its isotypes were determined. The optimized ginseng saponins-based nanoemulsion formulation consisted of ginseng saponins, IPM, Cremophor RH 40, glycerol and water (with the weight ratio of 2 : 4 : 17.8 : 17.8 : 58.4), which was a light yellow fluid. The shape of droplets was spherical under transmission electron microscopy with an average diameter of 72.20 nm and a polydispersity index of 0.052. The viscosity and pH value of it were 4.20 s and 6.02, respectively. And it showed good stability. When co-administered with OVA, no obvious side effects were observed in the mice immunized with ginseng saponin-based nanoemulsion. The serum levels of IgG, IgG1 and IgG2a antibody in the group of ginseng saponin-based nanoemulsion immunized mice was significantly increased compared to the groups of OVA and the saline solution of ginseng saponin. Compared with the adjuvant aluminium hydroxide, the serum levels of IgG and IgG1 antibodys in the groups of ginseng saponins-based nanoemulsion had no significant difference, but the level of IgG2a was obviously higher. ginseng saponin-based nanoemulsion could amplify the Th1 and Th2 immune responses, and can be used as the vaccine adjuvant.

Bioactive constituents of oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra.

PubMed

Wei, Juan-Hua; Zheng, Yun-Feng; Li, Cun-Yu; Tang, Yu-Ping; Peng, Guo-Ping

2014-01-01

Three new oleanane-type triterpene saponins, namely licorice-saponin M3 (1), licorice-saponin N4 (2), and licorice-saponin O4 (3), an artificial product (4), as well as five known triterpene glucuronides (5-9), were isolated from the roots of Glycyrrhiza glabra L. Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry, and by comparison with spectroscopic data reported in the literature. The inhibitory effects of the selected compounds on neuraminidase were evaluated, and the preliminary structure-activity relationship was also predicted.

Effect of glandular kallikrein on distal nephron HCO3- secretion in rats and on HCO3- secretion in MDCK cells.

PubMed

Vallés, P; Ebner, S; Manucha, W; Gutierrez, L; Marin-Grez, M

1997-11-01

Renal kallikrein is localized in the connecting tubule cells and secreted into the tubular fluid at late distal nephron segments. The present experiments were performed to further test the hypothesis that renal kallikrein reduces bicarbonate secretion of cortical collecting duct (CCD). The effect of orthograde injections of pig pancreatic kallikrein (1 or 3 micrograms/ml) into the renal tubular system was investigated. Urine fractions (Fr) were collected after a 2-min stop flow. Changes in the urine fraction with respect to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/ Fr:Ff polyfructosan) increased significantly in the first two urine fractions collected after glandular kallikrein administration (kallikrein, 1 microgram/ml, P < 0.05; kallikrein, 3 micrograms/ml, P < 0.01). HCO3- secretion of collecting ducts was significantly reduced dose dependently by orthograde and also reduced by retrograde pig pancreatic kallikrein administration. Release of kinins into the fractions was not affected by the retrograde kallikrein injection, even though the kallikrein activity increased considerably (2.26 +/- 0.2 vs. 1.55 +/- 0.2, P < 0.05). Adequacy of retrograde injections for delivering substances to the CCD was demonstrated by injecting colloidal mercury and detecting the appearance of this mercury in the renal cortex by transmission electron microscopy. The integrity of the renal tissue after a retrograde ureteral injection was confirmed by scanning electron microscopy. These results confirm and extend previous data (M. Marin-Grez and P. Vallés. Renal Physiol. Biochem. 17: 301-306, 1994; and M. Marin-Grez, P. Vallés, and P. Odigie. J. Physiol. 488: 163-170, 1995) showing that renal kallikrein reduces bicarbonate secretion at the CCD, probably by inhibiting HCO3- transported by a mechanism unrelated to its kininogenase activity. Support for this assessment was obtained in experiments testing the effect of kallikrein on the luminal bicarbonate secretion of a subpopulation of Madin-Darby canine kidney cells capable of extruding the anion. Kallikrein inhibited HCO3-/Cl- exchange, and the degree of inhibition was dose dependent. This inhibition occurred in the absence of kininogen in the bathing solution.

Lead poisoning among children of Santo Amaro, Bahia, Brazil in 1980, 1985, and 1992.

PubMed

Silvany-Neto, A M; Carvalho, F M; Tavares, T M; Guimarães, G C; Amorim, C J; Peres, M F; Lopes, R S; Rocha, C M; Raña, M C

1996-03-01

A cross-sectional epidemiologic survey conducted at the beginning of 1992 evaluated the status of lead intoxication among children from 1 to 5 years of age living within 500 meters of a primary lead smelter in the Brazilian city of Santo Amaro, Bahia. A total of 103 children in this age group were initially enrolled in the study; however, 2 were later excluded because they could not be located, and 1 was excluded from the statistical analyses for reasons noted below. The results were compared with those from similar surveys made in 1980 and 1985 in the same area with children of the same age. A blood sample was obtained from each child, the child's hematocrit and zinc protoporphyrin (ZPP) level were determined, and an interview questionnaire was used to collect information of clinical or epidemiologic interest from the child's mother or guardian. The geometric average ZPP was 65.5 micrograms/100 mL (geometric standard deviation = 1.7), a level far exceeding the upper limit of normality established by the U.S. Centers for Disease Control and Prevention of 30 micrograms/100 mL. One child was excluded from the statistical analyses because it exhibited an extremely high ZPP level (789 micrograms/100 mL). Higher average ZPP levels were found for girls, children with darker-skinned racial backgrounds, children from homes where smelter slag was commonly used around the house, children presenting pica, and children of smelter workers. Of the symptoms of lead poisoning investigated, only nervousness and easy irritability exhibited high frequencies among the children studied. However, the prevalence of above-normal ZPP levels suggestive of lead poisoning was 92.2% in 1980, 98.4% in 1985, and 97.0% in 1992. Hence, the apparent prevalence of lead poisoning continued very high in 1992, indicating that the control measures adopted were ineffective or that other unidentified and uncontrolled risk factors were playing an important role. Overall, however, the proportion of children with very high ZPP levels fell sharply, and that of children with moderately high levels also declined notably, indicating that the severity of the problem had been reduced even though new cases of intoxication continued to occur. The Santo Amaro smelter closed its doors in December 1993.

Detection of soluble antigens of Toxoplasma gondii by a four-layer modification of an enzyme immunoassay.

PubMed Central

Turunen, H J

1983-01-01

A sensitive four-layer modification of an enzyme immunoassay for the detection of soluble antigens of Toxoplasma gondii is described. Microtiter plates were sensitized with rabbit anti-toxoplasma immunoglobulins (6 micrograms/ml) used as the primary antibodies; guinea pig anti-toxoplasma immunoglobulins (6 micrograms/ml) were used as the secondary trapping antibodies. Horseradish peroxidase-conjugated anti-guinea pig immunoglobulins were used as the indicator antibodies. The specificity of the antigen assay was confirmed by using guinea pig immunoglobulins from preimmunization sera. The sensitivity of the antigen assay was found to be at least 10 ng of antigen protein per ml. The suitability of the method for detecting antigens of T. gondii in different specimens was studied by experimental toxoplasma infection in mice. Antigenic components of T. gondii could be detected in different tissue specimens from infected animals from the first day after infection onwards. Toxoplasma antigen in serum and urine samples from infected mice reached detectable levels on day 2 after infection followed by a linear increase in antigen concentration in succeeding samples. This method might offer a valuable aid for a rapid etiological diagnosis also in human cases of acute toxoplasmosis. PMID:6345574

Phytochemical analysis of Gymnema sylvestre and evaluation of its antimicrobial activity.

PubMed

Chodisetti, Bhuvaneswari; Rao, Kiranmayee; Giri, Archana

2013-01-01

Gymnema sylvestre (CS 149), known to be a rich source of saponins and other valuable phytochemicals, has been analysed for antimicrobial activity. The chloroform extracts of aerial and root parts of G. sylvestre exhibited higher antimicrobial activity as compared to diethyl ether and acetone. The root extracts of chloroform have shown competitive minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0.04-1.28 mg mL(-1) and 0.08-2.56 mg/mL, respectively, towards the pathogens. The GC-MS analysis of chloroform extracts has shown the presence of compounds like eicosane, oleic acid, stigmasterol and vitamin E.

[Clinical studies of flomoxef in the field of pediatrics].

PubMed

Ito, S; Mayumi, M; Mikawa, H

1987-08-01

Flomoxef (FMOX, 6315-S), a newly synthesized antibiotic which belongs to the oxacephem group, was clinically evaluated for its efficacy and safety in 17 patients with ages ranging from 1 month to 9 year-8-month who had bacterial infections. The results obtained were summarized as follows. 1. A pharmacokinetic study following 20 mg/kg FMOX administration by intravenous bolus injection showed that the half-life of FMOX (beta phase) was 39.8 minutes and the urinary excretion of FMOX in the first 6 hours was 76.5%. 2. FMOX was administered to 3 patients with pneumonia, 8 patients with bronchopneumonia, 2 patients with tonsillitis, 2 patients with pyelonephritis, one patient each with cervical lymphadenitis, and pustulosis associated with severe varicella at daily dosage levels of 61.9 approximately 87.2 mg/kg, divided into 3 or 4 administrations by intravenous bolus injection or by 30 minutes drip infusion. The clinical results of these 17 patients were as follows; excellent: 14 patients, good: 2 patients, poor: 1 patient. The efficacy rate was 94.1%. 3. No clinical adverse reaction was observed in any of the 17 patients. Neutropenia, eosinophilia, a slight elevation of GPT and slight elevations of GOT & GPT were observed in 1, 1, 1, and 2 patients, respectively. No abnormality in coagulation system was observed in any of 10 evaluable patients. 4. MICs of FMOX against 13 strains isolated from patients were as follows. MIC against 2 out of 3 strains of Streptococcus pneumoniae was 0.20 micrograms/ml and that of the remaining 1 strain was 0.39 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Countercurrent chromatography separation of saponins by skeleton type from Ampelozizyphus amazonicus for off-line ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry analysis and characterisation.

PubMed

de Souza Figueiredo, Fabiana; Celano, Rita; de Sousa Silva, Danila; das Neves Costa, Fernanda; Hewitson, Peter; Ignatova, Svetlana; Piccinelli, Anna Lisa; Rastrelli, Luca; Guimarães Leitão, Suzana; Guimarães Leitão, Gilda

2017-01-20

Ampelozizyphus amazonicus Ducke (Rhamnaceae), a medicinal plant used to prevent malaria, is a climbing shrub, native to the Amazonian region, with jujubogenin glycoside saponins as main compounds. The crude extract of this plant is too complex for any kind of structural identification, and HPLC separation was not sufficient to resolve this issue. Therefore, the aim of this work was to obtain saponin enriched fractions from the bark ethanol extract by countercurrent chromatography (CCC) for further isolation and identification/characterisation of the major saponins by HPLC and MS. The butanol extract was fractionated by CCC with hexane - ethyl acetate - butanol - ethanol - water (1:6:1:1:6; v/v) solvent system yielding 4 group fractions. The collected fractions were analysed by UHPLC-HRMS (ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry) and MS n . Group 1 presented mainly oleane type saponins, and group 3 showed mainly jujubogenin glycosides, keto-dammarane type triterpene saponins and saponins with C 31 skeleton. Thus, CCC separated saponins from the butanol-rich extract by skeleton type. A further purification of group 3 by CCC (ethyl acetate - ethanol - water (1:0.2:1; v/v)) and HPLC-RI was performed in order to obtain these unusual aglycones in pure form. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide.

PubMed Central

Gewirtz, A M; Calabretta, B; Rucinski, B; Niewiarowski, S; Xu, W Y

1989-01-01

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis. Images PMID:2523411

[Clinical evaluation of flomoxef in pediatrics and a study on the penetration into cerebrospinal fluid].

PubMed

Okada, T; Furukawa, S

1987-08-01

The transfer to cerebrospinal fluid of a new oxacephem antibiotic flomoxef (FMOX, 6315-S) and its clinical efficacy against bacterial infections were investigated. 1. In 3 cases of purulent meningitis, cerebrospinal fluid concentrations of FMOX after one shot intravenous injection of 100 mg/kg during the acute stage of infections were 5.12-6.32 micrograms/ml and ratios of FMOX in cerebrospinal fluid in serum were about 5%. During the recovery stage, cerebrospinal fluid concentrations were about 3.8 micrograms/ml and cerebrospinal fluid/serum ratios were about 3.5%. 2. In 1 case of purulent meningitis, the treatment with FMOX was clinically effective but this case was classified as "unevaluable" because other drug was used concomitantly. FMOX was rated effective in other 2 cases of purulent meningitis. Of 9 cases of pneumonia, FMOX was rated very effective in 8 cases and it was rated only effective in the other. Of 4 cases of bronchitis, the drug was rated very effective in 3 cases and only effective in the other. FMOX was rated very effective against 2 cases of tonsillitis, also. 3. As side effects, thrombocytosis was observed in 3 of 20 cases examined. All cases, however, were deemed unrelated to the FMOX treatment and the side effect was only transient as are often found in courses of recovery from infections.

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis.

PubMed Central

Shalit, I; Greenwood, R B; Marks, M I; Pederson, J A; Frederick, D L

1986-01-01

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed. These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD. In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients. PMID:2944477

Antimicrobial susceptibilities of Erysipelothrix rhusiopathiae isolated from pigs with swine erysipelas in Japan, 1988-1998.

PubMed

Yamamoto, K; Kijima, M; Yoshimura, H; Takahashi, T

2001-03-01

The susceptibility to 21 antimicrobial agents of 214 strains of Erysipelothrix rhusiopathiae isolated from pigs affected with swine erysipelas in Japan between 1988 and 1998 was determined. Ampicillin, cloxacillin, benzylpenicillin, ceftiofur, tylosin, enrofloxacin and danofloxacin were the most active agents [minimum inhibitory concentrations (MICs); < or = 0.025-0.78 microgram/ml], followed by cefazolin, virginiamycin, tiamulin, chloramphenicol, florphenicol and oxolinic acid (MICs; 0.1-25 micrograms/ml). Activity was poor or absent with kanamycin and sulfadimethoxine. Strains resistant to dihydrostreptomycin, erythromycin, clindamycin, lincomycin, oxytetracycline and doxycycline were detected. The susceptibilities to dihydrostreptomycin and oxytetracycline tended to decrease. Investigation of the differences in antimicrobial susceptibility of the 214 strains according to their serotypes, sources, isolation years and regions, showed that the strains resistant to dihydrostreptomycin were most frequently found in the strains of serotype 1a and in strains from septicaemic cases. Strains resistant to oxytetracycline were detected in all serotypes and all sources, and most of the strains resistant to erythromycin were detected in the strains of serotype 2. The frequency of strains resistant to dihydrostreptomycin gradually increased from 1988 to 1996, but then decreased between 1997 and 1998. The frequency of strains resistant to oxytetracycline was remained more than 38% from 1988 to 1998. It was suggested that the strains resistant to dihydrostreptomycin and oxytetracycline were distributed over almost all districts of Japan.

Metal exposures from aluminum cookware: An unrecognized public health risk in developing countries.

PubMed

Weidenhamer, Jeffrey D; Fitzpatrick, Meghann P; Biro, Alison M; Kobunski, Peter A; Hudson, Michael R; Corbin, Rebecca W; Gottesfeld, Perry

2017-02-01

Removing lead from gasoline has resulted in decreases in blood lead levels in most of the world, but blood lead levels remain elevated in low and middle-income countries compared to more developed countries. Several reasons for this difference have been investigated, but few studies have examined the potential contribution from locally-made aluminum cookware. In a previous study of cookware from a single African country, Cameroon, artisanal aluminum cookware that is made from scrap metal released significant quantities of lead. In this study, 42 intact aluminum cookware items from ten developing countries were tested for their potential to release lead and other metals during cooking. Fifteen items released ≥1 microgram of lead per serving (250mL) when tested by boiling with dilute acetic acid for 2h. One pot, from Viet Nam, released 33, 1126 and 1426 micrograms per serving in successive tests. Ten samples released >1 microgram of cadmium per serving, and fifteen items released >1 microgram of arsenic per serving. The mean exposure estimate for aluminum was 125mg per serving, more than six times the World Health Organization's Provisional Tolerable Weekly Intake of 20mg/day for a 70kg adult, and 40 of 42 items tested exceeded this level. We conducted preliminary assessments of three potential methods to reduce metal leaching from this cookware. Coating the cookware reduced aluminum exposure per serving by >98%, and similar reductions were seen for other metals as well. Potential exposure to metals by corrosion during cooking may pose a significant and largely unrecognized public health risk which deserves urgent attention. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of phthalate esters with endometriosis in Indian women.

PubMed

Reddy, B S; Rozati, R; Reddy, B V R; Raman, N V V S S

2006-05-01

To evaluate the possible association between phthalate esters (PEs) and the occurrence of endometriosis. Case-control study. Department of Reproductive Medicine, Bhagawan Mahavir Medical Research Centre, Maternal Health and Reproductive Institute and Department of Analytical R&D, Hetero Research Foundation, Hyderabad, Andhra Pradesh, India. Blood samples were collected from 49 infertile women with endometriosis (study group); 38 age-matched women without endometriosis (control group I) but with infertility related to tubal defects, fibroids, polycystic ovaries, idiopathic infertility and pelvic inflammatory diseases diagnosed by laparoscopy and a further group of 21 age-matched women (control group II) with proven fertility and no evidence of endometriosis and other gynaecological disorders during laparoscopic sterilisation. Concentrations of PEs were measured using gas chromatography. Evaluation of PEs concentrations in women with endometriosis compared with women free from the disease. Women with endometriosis showed significantly higher concentrations of di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBP), di-n-octyl phthalate (DnOP) and diethyl hexyl phthalate (DEHP) (mean 0.44 [SD 0.41]; 0.66 [SD 0.61]; 3.32 [SD 2.17]; 2.44 [SD 2.17] micrograms/ml) compared with control group I (mean 0.08 [SD 0.14]; 0.12 [SD 0.20]; 0; 0.50 [SD 0.80] micrograms/ml) and control group II (mean 0.15 [SD 0.21]; 0.11 [SD 0.22]; 0; 0.45 [SD 0.68] micrograms/ml). The correlation between the concentrations of PEs and different severity of endometriosis was strong and statistically significant at P < 0.05 for all four compounds (DnBP: r=+0.73, P < 0.0001; BBP: r=+0.78, P < 0.0001; DnOP: r=+0.57, P < 0.0001 and DEHP: r=+0.44, P < 0.0014). This study suggests that PEs may have an aetiological association with endometriosis.

Tetanus toxin interaction with human erythrocytes. II. Kinetic properties of toxin association and evidence for a ganglioside-toxin macromolecular complex formation.

PubMed

Lazarovici, P; Yavin, E

1985-01-25

The properties of tetanus toxin interaction with human erythrocytes supplemented with disialo- and trisialo-gangliosides have been investigated. Binding of toxin is linear with time for 1 h and is 3-4-fold higher at 37 degrees C than at 4 degrees C during incubation of long duration. It exhibits saturation at toxin concentrations between 0.1 and 1 microgram/ml; however, it is nonsaturable between 1 and up to 50 micrograms/ml. It is effectively prevented by free gangliosides and antibodies or by pretreatment with sialidase but is unaffected by a number of closely related ligands including toxoid and toxin fragments. NaCl (1 M) removes a great portion (86%) of cell-associated toxin while Triton X-100 extracts an additional fraction (30%) of the salt-resistant cell-bound toxin. The residual sequestred toxin after detergent extraction is sensitive to proteolytic degradation. The trypsin-stable fraction (1.5%) is biotoxic and may be indicative of internalization of toxin. A macromolecular complex of about 700 kDa containing toxin and gangliosides has been isolated and characterized by Sephacryl S-300 gel permeation chromatography, SDS-gel electrophoresis, immunoprecipitability and biotoxicity. This complex is obtained only in ganglioside-supplemented cells and not when free 3H-labeled GD1b is reacted with 125I-labeled toxin in solution in the absence of cells. The hydrophobicity properties acquired as a result of ganglioside-toxin interaction, presumably at the cell surface, suggest a conformational change of the toxin which may enable its penetration into the bilayer.

Pharmacological characterisation of extracts of coffee dusts.

PubMed Central

Zuskin, E; Duncan, P G; Douglas, J S

1983-01-01

The contractile or relaxant activities or both of aqueous extracts of green and roasted coffees were assayed on isolated guinea pig tracheal spirals. Contractile and relaxant activities were compared with histamine and theophylline, respectively. Green coffee extracts induced concentration dependent contraction, but the maximal tension never exceeded 76.3% +/- 5.2 of a maximal histamine contraction (0.69 +/- 0.07 g/mm2 v 0.52 +/- 0.05 g/mm2; p (0.01). One gram of green coffee dust had a biological activity equivalent to 1.23 +/- 0.1 mg of histamine. The pD2 value of histamine was -5.17 +/- 0.05. The potency of green coffee was unaffected by mepyramine maleate (1 micrograms/ml, final bath concentration) while that of histamine was reduced 500 fold. Tissues contracted with histamine were not significantly relaxed by green coffee extracts. By contrast, roasted coffee extracts induced concentration dependent relaxation of uncontracted and histamine contracted tissues. Tissues contracted with green coffee extracts were also completely relaxed by roasted coffee extracts. The pD2 value of theophylline was -4.10 +/- 0.03. The relaxant activity of 1 g of roasted coffee was equivalent to 1.95 +/- 0.16 mg of theophylline. The potency of these extracts was significantly reduced after propranolol (1 micrograms/ml; dose ratio 1.56). Our results show that coffee dust extracts have considerable biological activity which changes from a contractile to a relaxant action as a consequence of processing. The greater incidence of adverse reactions to green coffee dust(s) in coffee workers may be related to the contractile activity present in green coffee dust. PMID:6830717

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

PubMed Central

Khatuntseva, Elena A; Men’shov, Vladimir M; Shashkov, Alexander S; Tsvetkov, Yury E; Stepanenko, Rodion N; Vlasenko, Raymonda Ya; Shults, Elvira E; Tolstikov, Genrikh A; Tolstikova, Tatjana G; Baev, Dimitri S; Kaledin, Vasiliy A; Popova, Nelli A; Nikolin, Valeriy P; Laktionov, Pavel P; Cherepanova, Anna V; Kulakovskaya, Tatiana V; Kulakovskaya, Ekaterina V

2012-01-01

Summary Two new triterpenoid saponins 1 and 2 were isolated from the methanol extract of the roots of Acanthophyllum gypsophiloides Regel. These saponins have quillaic acid or gypsogenin moieties as an aglycon, and both bear similar sets of two oligosaccharide chains, which are 3-O-linked to the triterpenoid part trisaccharide α-L-Arap-(1→3)-[α-D-Galp-(1→2)]-β-D-GlcpA and pentasaccharide β-D-Xylp-(1→3)-β-D-Xylp-(1→3)-α-L-Rhap-(1→2)-[β-D-Quip-(1→4)]-β-D-Fucp connected through an ester linkage to C-28. The structures of the obtained saponins were elucidated by a combination of mass spectrometry and 2D NMR spectroscopy. A study of acute toxicity, hemolytic, anti-inflammatory, immunoadjuvant and antifungal activity was carried out. Both saponins 1 and 2 were shown to exhibit immunoadjuvant properties within the vaccine composition with keyhole limpet hemocyanin-based immunogen. The availability of saponins 1 and 2 as individual pure compounds from the extract of the roots of A. gypsophiloides makes it a prospective source of immunoactive agents. PMID:23015825

Benzimidazole condensed ring systems 10 (1). Synthesis and cytotoxic activity of some pyrido[1,2-a]benzimidazoles.

PubMed

Badawey, E S; Kappe, T

1995-01-01

As a part of research project on the synthesis of a number of pyrido[1,2-a]benzimidazole derivatives with possible antineoplastic activity and as a result of the interesting antineoplastic activity recorded for one such compounds (NSC 649900), some new pyrido[1,2-a]benzimidazoles were prepared and evaluated for such activity. Compound (11, NSC 660334) exhibited a moderate in vitro antineoplastic activity especially against most of the leukemia cell lines, while compound (10, VM30309) showed a good cytotoxic activity against Artina salina larvae (IC50 = 1.75 micrograms/ml).

Caprine blastocyst formation following intracytoplasmic sperm injection and defined culture.

PubMed

Keskintepe, L; Morton, P C; Smith, S E; Tucker, M J; Simplicio, A A; Brackett, B G

1997-08-01

Experiments were undertaken to develop intracytoplasmic sperm injection (ICSI) to produce caprine embryos out of the normal breeding season. Oocytes were obtained from 2-6 mm ovarian follicles at slaughter. Selected oocytes with two to four layers of cumulus cells were incubated in 1 ml of H-TCM199 supplemented with 10 micrograms each of oFSH and bLH (NHPP, NIDDK, NICHD, USDA) and 20% fetal bovine serum (FBS) in a thermos (38.5 degrees C) for 4.5 h during transportation. Then, oocytes were transferred into 75 microliters of freshly prepared maturation medium under paraffin oil and a mixture of 5% O2, 5% CO2 and 90% N2. Approximately 26 h after recovery oocytes were denuded by incubation with hyaluronidase (100 IU/ml) and pipetting and held at 38.5 degrees C for 90 min. Spermatozoa frozen in egg yolk extender were thawed in a 37 degrees C water bath for 15 s. Motile fractions were selected by swim-up, then incubated for 90 min in TALP with 10 micrograms heparin/ml. Each oocyte was positioned with its first polar body at 6 or 12 o'clock by a holding pipette. Sperm (1 microliter) were added to 10 microliters medium containing 10% polyvinylpyrrolidone. A sperm cell was aspirated into a pipette, and then injected head-first into the cytoplasm of an oocyte maintained in H-TCM199 + 20% FBS at 37 degrees C. Injected oocytes were transferred to HM and, after 90 min, cultured in 50 microliters of BSA-free synthetic oviduct fluid plus polyvinyl alcohol, citrate and non-essential amino acids. Results demonstrate that caprine blastocysts can be produced outside the breeding season by the use of frozen-thawed semen and injection of sperm cells with broken tails into ova followed by culture in defined medium.

Triterpenoid saponins from the rhizomes of Anemone flaccida and their inhibitory activities on LPS-induced NO production in macrophage RAW264.7 cells.

PubMed

Huang, Xiao-Jun; Tang, Jing-Qun; Li, Man-Mei; Liu, Qing; Li, Yao-Lan; Fan, Chun-Lin; Pei, Hong; Zhao, Hui-Nan; Wang, Ying; Ye, Wen-Cai

2014-01-01

A new ursane-type triterpenoid saponin, flaccidoside IV (1), and three new oleanane-type triterpenoid saponins, flaccidosides V-VII (2-4), along with 17 known saponins (5-21), were isolated from the rhizomes of Anemone flaccida. The structures of the new triterpenoid saponins were determined based on spectroscopic analyses and chemical methods. All the isolated saponins were tested for their inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages, and several bisdesmosidic oleanane-type triterpenoid saponins (2, 7, and 10) showed significant inhibitory activities, which indicated they had potential anti-inflammatory activities under their noncytotoxic concentrations in vitro.

Evaluation in vitro and in vivo of dimethicone transdermal therapeutic systems. Influence of propylene glycol on drug release.

PubMed

Ritschel, W A; Nayak, P M

1987-03-01

Coumarin-containing transdermal drug delivery systems were studied in vitro for drug release and in vivo in rats for drug absorption. The matrix of the transdermal delivery system, dimethicone, was a commercially available silicone elastomer. The devices containing 1, 3 and 5% coumarin released in vitro 8.8 (87.4%), 23.4 (74.5%) and 31.6 mg (63.3%) of drug within 24 h. The device containing 5% coumarin was selected for further studies in which 5, 10, 20, 30, 50 and 70% propylene glycol was added. Up to 20% propylene glycol content did not change the amount released. The preparations with 30, 50 and 70% propylene glycol released 69.3, 73.6 and 87.9%, respectively. The 50 and 70% preparations were physically not acceptable. Only the preparations containing 5% coumarin without propylene glycol and 5% coumarin and 30% propylene glycol in the elastomer were evaluated in vivo. The area under the blood level-time curve of the propylene glycol-containing system was twice that of the device without propylene glycol. Blood levels were maintained between about 2 micrograms/ml and 5 micrograms/ml during the time the device was kept on the skin (24 h).

Heart cells in culture: a model of myocardial iron overload and chelation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Link, G.; Pinson, A.; Hershko, C.

1985-08-01

The effect of iron loading and chelation was studied in heart cell cultures obtained from newborn rats. Radioactive iron uptake per 2 X 10(6) cells/24 hr was 3.8% for /sup 59/Fe-transferrin, 15.8% for /sup 59/Fe-ferric ammonium citrate (FeAC) at 20 micrograms Fe/ml in 20% serum, and 37.1% for /sup 59/FeAC at 20 micrograms Fe/ml in serum-free medium. About one third of the cellular radioactive iron was in ferritin and the rest in an insoluble lysosomal fraction. Iron uptake was almost completely inhibited by reducing the incubation temperature from 37 degrees C to 10 degrees C. Intracellular concentrations of malonyldialdehyde (MDA)more » were doubled after 15 minutes of iron loading and reached maximal concentrations at 3 hours. Conversely, iron mobilization by deferoxamine at concentrations ranging from 0.025 mmol/L to 0.3 mmol/L resulted in normalization of cellular MDA concentrations, in direct proportion to the amounts of iron removed. These findings indicate that cultured myocardial cells are able to assimilate large amounts of nontransferrin iron and that iron uptake and mobilization are associated with striking changes in lipid peroxidation as manifested by the respective increase and decrease in cellular MDA concentrations.« less

OCCURRENCE OF VANCOMYCIN RESISTANT ENTEROCOCCI IN ANIMAL FECES

EPA Science Inventory

A survey was conducted to determine the occurrence of vancomycin resistant Enterococci (VRE) in animal and human fecal samples. A selective agar mEI, and mEI supplemented with 4 micrograms/ml vancomycin was used in a membrane filtration procedure to determine quantitative levels ...

[Comparative effectiveness of antimicrobial action of antiseptics against pathogens of chronic purulent otitis media].

PubMed

Paliĭ, G K; Barilo, A S; Chesnokova, A A

1992-12-01

Comparable antimicrobial and disinfecting action of decamethoxine and silver preparations on pathogens of chronic purulent otitis media (CPOM) was studied. The clinical isolates of staphylococci proved to be most sensitive to decamethoxine whose MBcC conformed to 16.5 micrograms/ml. The antimicrobial action on Proteus spp. and Pseudomonas aeruginosa was less pronounced. The required concentrations for bactericidal action on these pathogens were 69 and 93.5 micrograms/ml, respectively. The antimicrobial activity of the silver preparations such as poviargol, collargol and protargol was low. Depending on the microbial species, the bactericidal effect of the silver preparations was 12-235 times lower than that of decamethoxin. It was also shown that decamethoxin had a high disinfecting action on CPOM pathogens. It was noted that decamethoxin had a marked ability to increase the bactericidal action of poviargol (by 2-14 times) and its disinfecting action (by 2 times) on Proteus spp., E. coli and Ps. aeruginosa.

Salicylic acid plasma levels following multiple doses of Norgesic Forte and aspirin.

PubMed

Harrison, L I; Kehe, C R; Goldlust, M B; Kvam, D C; Bianchine, J R

1983-01-01

Plasma salicyclic acid levels from the recommended multiple dose regimen of Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) were compared to those from an equivalent multiple dose regimen of aspirin alone in 24 volunteers. The drugs were administered double-blind so that side effects could also be compared. No statistically significant differences were found between Norgesic Forte and aspirin in peak or trough levels, time to peak level, area under the curve, or mean steady-state level of salicylic acid. Mean steady-state levels averaged 154 +/- 46 (+/- SD) and 152 +/- 49 micrograms/ml on days 5 and 10 following Norgesic Forte versus 161 +/- 49 and 154 +/- 47 micrograms/ml following aspirin. Thus, the aspirin in Norgesic Forte provides an anti-inflammatory amount of salicylic acid equivalent to that of plain aspirin. There was no evidence that the combination of orphenadrine citrate, caffeine, and aspirin in Norgesic Forte caused increased or unusual side effects compared with aspirin alone.

Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species.

PubMed Central

Trestman, I; Kaye, D; Levison, M E

1979-01-01

The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp. PMID:228593

Suppressive effects of chlorphenesin on lymphocyte function in mice and humans.

PubMed

Stites, D P; Brecher, G; Schmidt, L; Berger, F M

1979-12-01

The immunosuppressive action of chlorphenesin was investigated in a wide variety of in vitro assays for cellular immunity in humans and mice. Chlorphenesin, at doses of 20-50 micrograms/ml, inhibited mitogenic responses of both mouse and human B and T cells. These doses did not kill cells exposed to the drug for 72 hr. Mixed lymphocyte reactions in inbred strains of mice and in unrelated humans were also inhibited at concentrations of about 50 micrograms/ml. However, the generation of cytotoxic T cells in cell-mediated lympholysis assays was not inhibited to the same degree as proliferation in mixed lymphocyte reaction and the cytotoxic potential of presensitized mouse T cells for allogeneic targets was totally unaffected. These studies suggest that chlorphenesin may have a broad spectrum of suppressive effects both on T and B cells and that the predominant inhibition of proliferative responses in these cells may reduce the expansion of clones of immunocompetent cells in vivo.

Ex vivo study of serum bactericidal titers and killing rates of daptomycin (LY146032) combined or not combined with amikacin compared with those of vancomycin.

PubMed Central

Van der Auwera, P

1989-01-01

Twelve volunteers, in two groups of six, received daptomycin at a dose of 1 or 2 mg/kg. In addition, they received in a randomly allocated order amikacin (500 mg), daptomycin-amikacin, and vancomycin (500 mg). Thirty-five clinical isolates, including Staphylococcus aureus, S. epidermidis, Corynebacterium sp. group JK, and Enterococcus faecalis, were tested in vitro for the measure of the serum bactericidal titers and killing rates. The mean peak concentrations of daptomycin in serum 1 h after the administration of 1 and 2 mg/kg were 11 and 20 micrograms/ml, respectively. At 24 h after the administration of 2 mg/kg, the mean level in serum was 1.9 micrograms/ml, which is higher than the MICs for susceptible pathogens. Daptomycin and amikacin provided identical concentrations in serum whether given alone or in combination. Among the six regimens tested, those including daptomycin provided the highest and the most prolonged serum bactericidal titers against S. aureus, S. epidermidis, and E. faecalis. The killing rates measured by the killing curves were correlated with the concentration/MIC and concentration/MBC ratios of daptomycin for all strains tested. Significant killing occurred once the concentration of daptomycin in the serum 4- to 6-fold the MIC or 1- to 1.2-fold the MBC. The combination of daptomycin and amikacin had no effect on either the serum bactericidal titers or the rates of killing. Only vancomycin provided significant killing of the strains of Corynebacterium sp. group JK. PMID:2556079

Physicochemical, Antioxidant, and Cytotoxic Properties of Xao Tam Phan (Paramignya trimera) Root Extract and Its Fractions.

PubMed

Nguyen, Van Tang; Sakoff, Jennette A; Scarlett, Christopher J

2017-04-01

Xao tam phan (Paramignya trimera (Oliv.) Guillaum) has been used as a medicinal plant for cancer prevention and treatment in recent years. The objective of this study was to determine the physicochemical, antioxidant, and cytotoxic properties of crude P. trimera root (PTR) extract and its fractions using MeOH as a solvent and microwave-assisted extraction as an advanced technique for preparation of the PTR extract. The results showed that the PTR extract had high contents of saponins, phenolics, flavonoids, and proanthocyanidins (7731.05 mg escin equiv. (EE), 238.13 mg gallic acid equiv. (GAE), 81.49 mg rutin equiv., and 58.08 mg catechin equiv. (CE)/g dried extract, resp.). Antioxidant activity of PTR extract was significantly higher (P < 0.05) than those of four its fractions and ostruthin, a key bioactive compound in the P. trimera, while potent cytotoxic capacity of PTR extract on various cancer cell lines in terms of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed with GI 50 values ranging from 15 to 32 μg/ml. Cytotoxic potential on pancreatic cancer cells of PTR extract (100 - 200 μg/ml) was significantly higher (P < 0.05) than those of its four fractions (50 μg/ml), ostruthin (20 μg/ml) and gemcitabine (50 nm), and being comparable to a saponin-enriched extract from quillajia bark, a commercial product. Based on the results achieved, we can conclude that the PTR extract is a potential source for application of in the nutraceutical, medical, and pharmaceutical industries. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Two new triterpenoid saponins from the aerial parts of Anemone taipaiensis.

PubMed

Li, Hui; Wang, Xiao-Yang; Wang, Xia-Yin; Hua, Dong; Liu, Yang; Tang, Hai-Feng

2015-05-01

Phytochemical study on the aerial parts of Anemone taipaiensis for the first time led to the isolation of two new oleanane-type triterpenoid saponins 1 and 2, together with four known saponins (3-6). Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Saponins 2-4 exhibited cytotoxicity against human glioblastoma U251MG cell line with IC50 values ranging from 1.56 to 80.62 μM.

Black-pigmented Bacteroides spp. in human apical periodontitis.

PubMed Central

Haapasalo, M; Ranta, H; Ranta, K; Shah, H

1986-01-01

The incidence of black-pigmented (BP) Bacteroides spp. in 62 human dental root canal infections (35 acute and 27 clinically asymptomatic cases of apical periodontitis) in 57 adults was studied. Altogether 37 strains of BP Bacteroides were found in 31 infections, always in mixed anaerobic infections. Two different BP Bacteroides species were present in six infections. B. intermedius was most frequently isolated (15 of 62 canals; 24%) followed by B. denticola which was present in 12 cases. Asaccharolytic BP Bacteroides species, B. gingivalis and B. endodontalis, were found in eight cases. BP Bacteroides species were found both from symptomatic and asymptomatic infections, but there were also several symptomatic cases from which BP Bacteroides species were not isolated. B. gingivalis and B. endodontalis were present only in acute infections, B. intermedius was found both in symptomatic and asymptomatic infections, and B. denticola occurred mostly in asymptomatic infections. BP Bacteroides species were isolated initially from 9 of the 11 teeth with symptoms at 1 week, but only from 22 of the 51 teeth that were symptomless at 1 week. Two strains of B. denticola were resistant to penicillin G at a concentration of 2.4 micrograms/ml, but the MIC of penicillin G for all other strains was 0.6 micrograms/ml or lower. Forty-two randomly selected patients received penicillin V (oral administration, 650 mg, three times daily) during the first week of endodontic therapy. Penicillin had no effect on the occurrence of symptoms after 1 week compared with the control group (20 patients). PMID:3721577

Black-pigmented Bacteroides spp. in human apical periodontitis.

PubMed

Haapasalo, M; Ranta, H; Ranta, K; Shah, H

1986-07-01

The incidence of black-pigmented (BP) Bacteroides spp. in 62 human dental root canal infections (35 acute and 27 clinically asymptomatic cases of apical periodontitis) in 57 adults was studied. Altogether 37 strains of BP Bacteroides were found in 31 infections, always in mixed anaerobic infections. Two different BP Bacteroides species were present in six infections. B. intermedius was most frequently isolated (15 of 62 canals; 24%) followed by B. denticola which was present in 12 cases. Asaccharolytic BP Bacteroides species, B. gingivalis and B. endodontalis, were found in eight cases. BP Bacteroides species were found both from symptomatic and asymptomatic infections, but there were also several symptomatic cases from which BP Bacteroides species were not isolated. B. gingivalis and B. endodontalis were present only in acute infections, B. intermedius was found both in symptomatic and asymptomatic infections, and B. denticola occurred mostly in asymptomatic infections. BP Bacteroides species were isolated initially from 9 of the 11 teeth with symptoms at 1 week, but only from 22 of the 51 teeth that were symptomless at 1 week. Two strains of B. denticola were resistant to penicillin G at a concentration of 2.4 micrograms/ml, but the MIC of penicillin G for all other strains was 0.6 micrograms/ml or lower. Forty-two randomly selected patients received penicillin V (oral administration, 650 mg, three times daily) during the first week of endodontic therapy. Penicillin had no effect on the occurrence of symptoms after 1 week compared with the control group (20 patients).

Soyasaponin Bh, a Triterpene Saponin Containing a Unique Hemiacetal-Functional Five-Membered Ring from Glycine max (Soybeans)

USDA-ARS?s Scientific Manuscript database

Soybeans (Glycine max L. Merill) and soy-based food products are major dietary sources of saponins. An oleanane triterpenoid saponin, soyasaponin Bh (1) containing a unique five-membered ring with a hemiacetal functionality together with seven known saponins were isolated from soybeans. Their struct...

Effects of neonatal hyperthyroidism on the development of the hypothalamic-pituitary-thyroid axis in the rat.

PubMed

Dussault, J H; Coulombe, P; Walker, P

1982-03-01

The acute and latent effects of neonatal hyperthyroidism (NH) on the hypothalamic-pituitary-thyroid axis were studied in the rat after treatment of newborn animals with L-T4 (0.4 microgram/g BW, daily) for a period of 12 days. NH was associated with a permanent reduction in body weight in both male and female rats, in addition to a delay in the attainment of peak concentrations of hypothalamic TRH and pituitary and serum TSH. Serum TSH, T4, and T3 concentrations also were significantly and permanently reduced in NH animals (P less than 0.01) after cessation of L-T4 treatment. The serum TSH secretory response to 1 microgram synthetic TRH also was evaluated in 120-day-old control and NH rats, before and after the administration of L-T4 (0.6 microgram/100 g BW for 7 days) or propylthiouracil (0.05% in the drinking water for 14 days). In the baseline state, adult NH rats had a net secretory response similar to that of controls (189.0 +/- 31.3 vs. 227.0 +/- 29.3 microgram/ml . min). Administration of T4 significantly decreased while propylthiouracil treatment significantly increased the net TSH secretory response of NH rats compared to similarly treated control rats. These data are compatible with the hypothesis that NH leads to a permanent resetting of the regulatory set-point for pituitary TSH secretion and to increased sensitivity to the feedback inhibitory effects of thyroid hormones.

LC-MS-based quantification method for Achyranthes root saponins.

PubMed

Kawahara, Yuki; Hoshino, Tatsuro; Morimoto, Hidetaka; Shinizu, Tomofumi; Narukawa, Yuji; Fuchino, Hiroyuki; Kawahara, Nobuo; Kiuchi, Fumiyuki

2016-01-01

A liquid chromatography mass spectrometry (LC-MS) method was developed for simultaneous quantitative analysis of Achyranthes root saponins: chikusetsusaponins IVa (1) and V (2), achyranthosides B (3), C (4), D (5), E (6), and G (7), sulfachyranthosides B (8) and D (9), and betavulgarosides II (10) and IV (11). Satisfactory separation of the saponins was achieved with the use of a volatile ion-pair reagent (dihexyl ammonium acetate) on a phenyl-hexylated silica gel column, and the amounts of saponins extracted under three different conditions were determined. When Achyranthes root was extracted with water at room temperature, achyranthosides B (3) and D (5) were the major saponins, and smaller amounts of other saponins (4, 6-11) were present. However, the amounts of chikusetsusaponins (1 and 2) were negligible. Under the condition to make a standard decoction of a Kampo formula, the major saponins were achyranthosides B (3), C (4), and D (5), and small amounts of chikusetsusaponins IVa (1) and V (2) appeared, whereas prolonged heating largely increased the amounts of chikusetsusaponins. This method can be used for quality control of Achyranthes root.

Saponin determination, expression analysis and functional characterization of saponin biosynthetic genes in Chenopodium quinoa leaves.

PubMed

Fiallos-Jurado, Jennifer; Pollier, Jacob; Moses, Tessa; Arendt, Philipp; Barriga-Medina, Noelia; Morillo, Eduardo; Arahana, Venancio; de Lourdes Torres, Maria; Goossens, Alain; Leon-Reyes, Antonio

2016-09-01

Quinoa (Chenopodium quinoa Willd.) is a highly nutritious pseudocereal with an outstanding protein, vitamin, mineral and nutraceutical content. The leaves, flowers and seed coat of quinoa contain triterpenoid saponins, which impart bitterness to the grain and make them unpalatable without postharvest removal of the saponins. In this study, we quantified saponin content in quinoa leaves from Ecuadorian sweet and bitter genotypes and assessed the expression of saponin biosynthetic genes in leaf samples elicited with methyl jasmonate. We found saponin accumulation in leaves after MeJA treatment in both ecotypes tested. As no reference genes were available to perform qPCR in quinoa, we mined publicly available RNA-Seq data for orthologs of 22 genes known to be stably expressed in Arabidopsis thaliana using geNorm, NormFinder and BestKeeper algorithms. The quinoa ortholog of At2g28390 (Monensin Sensitivity 1, MON1) was stably expressed and chosen as a suitable reference gene for qPCR analysis. Candidate saponin biosynthesis genes were screened in the quinoa RNA-Seq data and subsequent functional characterization in yeast led to the identification of CqbAS1, CqCYP716A78 and CqCYP716A79. These genes were found to be induced by MeJA, suggesting this phytohormone might also modulate saponin biosynthesis in quinoa leaves. Knowledge of the saponin biosynthesis and its regulation in quinoa may aid the further development of sweet cultivars that do not require postharvest processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute intoxication and recovery following massive turpentine ingestion: clinical and toxicological data.

PubMed

Troulakis, G; Tsatsakis, A M; Tzatzarakis, M; Astrakianakis, A; Dolapsakis, G; Kostas, R

1997-06-01

Reports of acute turpentine intoxication, particularly containing toxicological data, are poorly verified in the literature. This report regards the intentional massive ingestion of turpentine solution in an elderly woman who developed mainly central nervous system manifestations, then had an impressive and quick total recovery although the initial prognosis was very bad. Blood and urine levels of turpentine were monitored using gas chromatography and at the early toxicogenic stage were 28 micrograms/mL and 15 micrograms/mL respectively. Gastric fluid analysis on admission to the hospital revealed the presence of approximately 200 mL turpentine in the intestine. A review of earlier reports is given.

Effect of dietary karaya saponin on serum and egg yolk cholesterol in laying hens.

PubMed

Afrose, S; Hossain, M S; Tsujii, H

2010-12-01

1. The objective of the study was to investigate the effect of dietary karaya saponin on cholesterol deposition in laying hens. 2. A total of 40 Boris Brown hens were randomly assigned at 20 weeks of age to 4 treatment groups and fed on diets supplemented with 0 (control), 25, 50 or 75 mg/kg karaya saponin for an 8-week experimental period. 3. After 8 weeks of dietary supplementation, karaya-saponin-treated groups had significantly lower serum cholesterol (23·0%) and triglycerides but increased high density lipoproteins cholesterol concentration than controls, irrespective of karaya saponin content in the diet. Egg yolk cholesterol and triglycerides were also significantly reduced by dietary karaya saponin. Hepatic cholesterol and triglycerides were significantly reduced by karaya saponin but bile acids concentration in the faeces and liver were significantly increased by karaya saponin. The concentrations of oleic, linoleic and linolenic acids in the yolk were greater in hens receiving karaya saponin than in controls. Karaya saponin significantly increased egg production, feed efficiency and yolk colour compared with controls. Karaya saponin tended to increase egg weight, feed consumption, Haugh units, albumen weight and yolk index. 4. In conclusion, karaya saponin is a potential agent for reducing yolk cholesterol concentration together with an overall increase of production performance and improvement in egg quality.

Where does the toxicity come from in saponin extract?

PubMed

Jiang, Xiaogang; Cao, Yi; Jørgensen, Louise von Gersdorff; Strobel, Bjarne W; Hansen, Hans Chr Bruun; Cedergreen, Nina

2018-08-01

Saponin-rich plant extracts contain bioactive natural compounds and have many applications, e.g. as biopesticides and biosurfactants. The composition of saponin-rich plant extracts is very diverse, making environmental monitoring difficult. In this study various ecotoxicity data as well as exposure data have been collected to explore which compounds in the plant extract are relevant as plant protection agents and furthermore to clarify which compounds may cause undesired side-effects due to their toxicity. Hence, we quantified the toxicity of different fractions (saponins/non-saponins) in the plant extracts on the aquatic crustacean Daphnia magna and zebrafish (Danio rerio) embryos. In addition, we tested the toxicity changes during saponin degradation as well. The results confirm that saponins are responsible for the majority of toxicity (85.1-93.6%) of Quillaja saponaria extract. We, therefore, suggest saponins to be the main target of saponin-rich plant extracts, for instance in the saponin-based biopesticide regulation. Furthermore, we suggest that an abundant saponin fraction, QS-18 from Q. saponaria, can be a key monitoring target to represent the environmental concentration of the saponins, as it contributes with 26% and 61% of the joint toxicity to D. magna and D. rerio, respectively out of the total saponins. The degradation products of saponins are 3-7 times less toxic than the parent compound; therefore the focus should be mainly on the parent compounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibition of amyloid β aggregation and protective effect on SH-SY5Y cells by triterpenoid saponins from the cactus Polaskia chichipe.

PubMed

Fujihara, Koji; Koike, Shin; Ogasawara, Yuki; Takahashi, Kunio; Koyama, Kiyotaka; Kinoshita, Kaoru

2017-07-01

Alzheimer's disease (AD) destroys brain function, especially in the hippocampus, and is a social problem worldwide. A major pathogenesis of AD is related to the accumulation of amyloid beta (Aβ) peptides, resulting in neuronal cell death in the brain. Here, we isolated four saponins (1-4) and elucidated their structures from 1D and 2D NMR and HRFABMS spectral data. The structures of 1 and 2 were determined as new saponins which have cochalic acid as the aglycon, and 3 was determined as a new saponin with oleanolic acid as the aglycon. Compound 4 was confirmed as the known saponin chikusetsusaponin V (=ginsenoside R 0 ). Isolated saponins (1-4) and six previously reported saponins (5-10) were tested for their inhibitory effects of Aβ aggregation and their protective effects on SH-SY5Y cells against Aβ-associated toxicity. As the results, compounds 3 and 4 showed inhibitory effect of Aβ aggregation and compounds 5-8 exerted the protective effects on SH-SY5Y cells against Aβ-associated toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary excretion of unmetabolized benzene as an indicator of benzene exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghittori, S.; Fiorentino, M.L.; Maestri, L.

1993-03-01

Benzene concentrations in urine samples (Cu, ng/L) from 110 workers exposed to benzene in chemical plants and gasoline pumps were determined by injecting urine supernate into a gas chromatograph. The urine was saturated with anhydrous N2SO4 to facilitate the passage of benzene in the air over the urine. The solvent was stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap tube) by means of a suction pump (flow rate 150 ml/m). Wash-up of the head space was achieved by simultaneous intake of filtered air through charcoal. Benzene was thermically desorbed and injected in a column (thermal tubemore » disorder, Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1, 60 m length, 0.75 mm ID, 1 microns film thickness; GC Dani 8580-FID). Benzene concentrations in the urine from 40 non-exposed subjects (20 smokers > 20 cigarette/d and 20 nonsmokers) were also determined [median value of 790 ng/L (10.17 nmol/L) and 131 ng/L (1.70 nmol/L), respectively]. The 8-h time-weighted exposure intensity (Cl, micrograms/m3) of individual workers was monitored by means of charcoal tubes. The median value for exposure to benzene was 736 micrograms/m3 (9.42 mumol/m3) [geometric standard deviation (GSD) = 2.99; range 64 micrograms/m3 (0.82 mumol/m3) to 13,387 micrograms/m3 (171.30 mumol/m3)]. The following linear correlation was found between benzene concentrations in urine (Cu, ng/L) and benzene concentrations in the breathing zone (Cl, micrograms/m3): log(Cu) = 0.645 x log(Cl) + 1.399 r = .559, n = 110, p < .0001 With exclusion of workers who smoked from the study, the correlation between air benzene concentration and benzene measured in urine was: log(Cu) = 0.872 x log(Cl) + 0.6 r = .763, n = 63, p < .0001 The study results indicate that the urinary level of benzene is an indicator of occupational exposure to benzene.« less

Hormonal characteristics of free-ranging female lions (Panthera leo) of the Serengeti Plains and Ngorongoro Crater.

PubMed

Brown, J L; Bush, M; Packer, C; Pusey, A E; Monfort, S L; O'Brien, S J; Janssen, D L; Wildt, D E

1993-01-01

Pituitary responses to gonadotrophin-releasing hormone (GnRH) and prolactin and steroid secretory profiles were examined in two populations of adult, female lions in the Serengeti (one outbred in the Serengeti Plains and one inbred in the Ngorongoro Crater) to determine whether reductions in genetic variability adversely affected endocrine function. GnRH-induced gonadotrophin secretion was also examined after adrenocorticotrophic hormone (ACTH) treatment to determine whether acute increases in serum cortisol altered pituitary function. Anaesthetized lions were administered (i) saline i.v. after 10 and 100 min of blood sampling, (ii) saline at 10 min and GnRH (1 micrograms kg-1 body weight) after 100 min; or (iii) ACTH (3 micrograms kg-1) at 10 min and GnRH after 100 min of sampling. Basal serum cortisol and basal and GnRH-induced gonadotrophin secretion were similar (P > 0.05) between females of the Ngorongoro Crater and Serengeti Plains. After ACTH, serum cortisol increased two- to threefold over baseline values and the response was unaffected (P > 0.05) by location. ACTH-induced increases in serum cortisol had no effect on subsequent basal or GnRH-stimulated luteinizing hormone (LH) or follicle-stimulating hormone (FSH) secretion. Overall mean serum progesterone concentrations ranged from 0.2 to 5.4 ng ml-1 with the exception of four females (two in the Serengeti and two in the Crater; progesterone range, 18.4-46.5 ng ml-1) that were presumed pregnant (three of these females were observed nursing cubs several weeks later).(ABSTRACT TRUNCATED AT 250 WORDS)

Steroidal Saponins from the Rhizomes of Aspidistra typica

PubMed Central

Zhao, Yang; Zhao, Jian-Yuan; Zhang, Jie; Pang, Xu; Yu, He-Shui; Jia, De-Xian; Liu, Chao; Yu, Li-Yan; Ma, Bai-Ping

2016-01-01

Eleven new furostanol saponins, typaspidosides B-L (1–11), one new spirostanol saponin, typaspidoside M (12), and five known spirostanol saponins, 25S-atropuroside (13), neoaspidistrin (14), (25S)-pratioside D1 (15), 25S-aspidistrin (16) and 25S-neosibiricoside (17) were isolated from the rhizomes of Aspidistra typica Baill. The structures of the new compounds were established using 1D and 2D NMR (1H-1H COSY, HMQC, HMBC and ROESY) spectroscopy, high resolution mass spectrometry, and chemical methods. The aglycones of 1–3 (unusual furostanol saponins with opened E ring type), 9 and 10 (the methoxyl substituent at C-23 position) were found, identified from natural products for the first time. Moreover, the anti-HIV activities of the isolated steroidal glycosides were assessed, and compounds 13, 14, 16 and 17 exhibited high active against HIV-1. PMID:26937954

Application of saponin biosurfactant and its recovery in the MEUF process for removal of methyl violet from wastewater.

PubMed

Samal, Kulbhushan; Das, Chandan; Mohanty, Kaustubha

2017-12-01

The potential of saponin, a biosurfactant, in the micellar enhanced ultrafiltration (MEUF) process was tested systematically for removal of methyl violet from wastewater. For this, the aqueous extract of reetha (Sapindus mukorossi) pericarp which contains saponin was used as the biosurfactant. First, the micellar solubilization of methyl violet in saponin micelles was investigated in terms of molar solubilization power (SP) of saponin. It was observed that the adsorption of methyl violet on the agglomerates of saponin micelles was mainly responsible for the enhanced solubilization. The Gibbs free energy of solubilization (calculated as -29.63 kJ mol -1 ) suggested that process was feasible and spontaneous. The MEUF experiments were performed in batch as well as continuous mode using saponin biosurfactant, and the effect of operating parameters on permeate flux and solute retention were evaluated. The removal of methyl violet in MEUF process was >99% achieved with 10 kDa polyethersulfone (PES) membrane for feed dye concentration of 250 mg L -1 at studied conditions. Finally, the saponin in permeate was recovered using n-heptane and n-butanol by solvent extraction process. The solvent n-butanol showed better extraction efficiency as compared to n-heptane for saponin extraction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

PubMed

Cornell, R P; McClellan, C C

1982-12-01

Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.

[Biological monitoring of occupational exposure to sevoflurane].

PubMed

Imbriani, M; Zadra, P; Negri, S; Alessio, A; Maestri, L; Ghittori, S

2001-01-01

Sevoflurane has been used in the last few years in brief surgical operations, either alone or in combination with nitrous oxide. Occupationally exposed groups include anesthesiologists, surgeons and operating room nurses. In 1977 the National Institute for Occupational Safety and Health (NIOSH) recommended that occupational exposure to halogenated anesthetic agents (halothane, enflurane, and isoflurane), when used as the sole anesthetic, should be controlled so that no worker would be exposed to time-weighted average concentrations greater than 2 ppm during anesthetic administration. When halogenated anesthetics are associated with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5 ppm. We think these recommendations can be extended to sevoflurane. Metabolism of sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary metabolites of sevoflurane have been identified: inorganic fluoride (which, however, is not specific) and a non-volatile compound that yields hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In order to investigate the role of urinary HFIP as an indicator of occupational exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating room staffs. The measurements of the time-weighted average of CI in the breathing zone were made by means of diffusive personal samplers. Each sampler was exposed during the whole working period. Sevoflurane was desorbed with CS2 from charcoal and the concentrations were measured on a gas chromatograph (GC) equipped with a mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as follows: injector column temperature = 200 degrees C; column temperature = 30 degrees C; carrier gas = helium; injection technique of samples = splitless. The analytical conditions for the MSD were the following: ion mass monitored = 131 m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu; electromultiplier = 400 V. Urine samples were collected near the end of the shift and were analyzed for HFIP by head-space gas chromatography after glucuronide hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8 ml headspace vials. The vials were immediately capped, vortexed, and loaded into the headspace autosampler. Samples were maintained at 100 degrees C for 30 min, after which glucuronide hydrolysis was 99% complete. Analyses were performed on a GC equipped with a MSD. The analytical conditions for urine analysis were as follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm, length 25 m); column temperature = 35 degrees C; carrier gas = helium. The analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range = 0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for sevoflurane. According to our experimental results, HFIP values of 488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane concentrations of 2 and 0.5 ppm respectively.

Cuspidate A, new anti-fungal triterpenoid saponin from Lepidagathis cuspidata.

PubMed

Rattan, Rajeev; Inder Fozdar, Bharat; Gautam, Veena; Sharma, Ritika; Kumar, Dinesh; Sharma, Upendra

2017-04-01

One new triterpenoid saponin named cuspidate A (1) along with a known oleanane-based triterpenoid saponin clemontanoside-C were isolated from the roots of Lepidagathis cuspidata. The structure of new compound (1) was established after detailed analysis of spectroscopic data including 1D and 2D NMR spectra. This is the first report on clemontanoside-C from this genus. These saponins were found to be effective against the selected fungal strains Aspergillus flavus, Rhizopus stolinifer, Penicillum nodatum, Aspergillus fumigates. Compound 1 showed better activity, comparable to the synthetic drug, while compound 2 showed a moderate effect against all studied fungal strains.

Structure revision of hupehensis saponin F and G and characterization of new trace triterpenoid saponins from Anemone hupehensis by tandem electrospray ionization mass spectrometry.

PubMed

Li, Fu; Liu, Xin; Tang, Minghai; Chen, Bin; Ding, Lisheng; Chen, Lijuan; Wang, Mingkui

2012-05-15

Electrospray ionization ion-trap tandem mass spectrometry (ESI-MS(n)) was first employed for reinvestigating the structures of hupehensis saponin F and G previously isolated from Anemone hupehensis in our lab. Hupehensis saponin G was determined to contain one more trisaccharide unit (Rha-(1→4)-Glc-(1→6)-Glc-), not a glucose residue, than saponin F based on their molecular weights deduced from their [M+Na](+) ions in ESI-MS spectra. The (2,4)A(4α)-ion at m/z 551.3 formed by retro-Diels-Alder (RDA) rearrangement in positive mode illustrated that the C-28 sugar chains of the two saponins were composed of trisaccharide repeating moieties with (1→4) linkages rather than (1→3) linkages. The interpretation of 2D-NMR spectra of the two compounds also confirmed the results obtained by ESI-MS(n). Moreover, from the water soluble part of A. hupehensis, two novel triterpene saponins were tentatively characterized to contain 4 and 5 (1→4)-linked above trisaccharide repeating moieties at C-28 position according to their ESI-MS(n) behaviors, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antimicrobial activity of saponins produced by two novel endophytic fungi from Panax notoginseng.

PubMed

Jin, Zhaoxia; Gao, Lin; Zhang, Lin; Liu, Tianyi; Yu, Fang; Zhang, Zongshen; Guo, Qiong; Wang, Biying

2017-11-01

Endophytes in plants may be co-producer of the bioactive compounds of their hosts. We conducted a study to bioprospect for saponin-producing endophytic fungi from Panax notoginseng and evaluate the antimicrobial activity of saponins. Two novel fungal endophytes, Fusarium sp. PN8 and Aspergillus sp. PN17, were isolated from traditional Chinese medicinal herb P. notoginseng. After eight days of fermentation, the total saponins produced in the culture broth of PN8 and PN17 were 1.061 and 0.583 mg mL -1 , respectively. The saponin extracts exhibited moderate to high (inhibition zone diameter 15.7-28.4 mm, MIC 1.6-12.5 mg mL -1 ) antimicrobial activity against pathogens tested. Further analysis showed that triterpenoid saponins produced by Fusarium PN8 were Rb 1 , Rd and 20(S)-Rg 3 , while Aspergillus PN17 had the ability to synthesise ginsenoside Re, Rd and 20(S)-Rg 3 . The isolated endophytes may be used as potential sources for microbial production of plant secondary metabolites and for antimicrobial agents.

Bioactive oleanane-type saponins from the rhizomes of Anemone taipaiensis.

PubMed

Wang, Xiao-Yang; Gao, Hui; Zhang, Wei; Li, Yuan; Cheng, Guang; Sun, Xiao-Li; Tang, Hai-Feng

2013-10-15

Investigation of the n-BuOH extract of the rhizomes of Anemone taipaiensis led to the isolation of five new oleanane-type triterpenoid saponins (1-5), together with seven known saponins (6-12). Their structures were determined by the extensive use of (1)D and (2)D NMR experiments along with ESIMS analyses and acid hydrolysis. The aglycone of 1, 2 and 4 was determined as siaresinolic acid, which was reported in this genus for the first time. The cytotoxicities of the saponins 1-12, prosapogenins 4a, 5a, 10a-12a and sapogenins siaresinolic acid (SA), oleanolic acid (OA), hederagenin (HE) were evaluated against five human cancer cell lines, including HepG2, HL-60, A549, HeLa and U87MG. The monodesmosidic saponins 6-8, 5a, 10a-12a and sapogenins SA, OA, HE exhibited cytotoxic activity toward all cancer cell lines, with IC50 values ranging from 2.25 to 57.28 μM. Remarkably, the bisdesmosidic saponins 1-4 and 9 showed selective cytotoxicity against the U87MG cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

/sup 45/Ca distribution and transport in saponin skinned vascular smooth muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stout, M.A.; Diecke, F.P.

1983-04-01

/sup 45/Ca distribution and transport were studied in chemically skinned strips of caudal artery from Kyoto Wistar rats. Sarcolemmal membranes were made hyperpermeable by exposure for 60 min to solutions containing 0.1 mg/ml of saponin. Skinned helical strips responded with graded contractions to changes in ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid buffered free Ca solutions (10(-7) to 10(-5) M) and were sensitive to the Mg-ATP concentration. Tissues loaded in the presence of 10(-7) M Ca contracted in response to 10 mM caffeine. These experiments indicate the strips are skinned and possess a functional regulatory and contractile system and an intact Camore » sequestering system. /sup 45/Ca distributes in three compartments in skinned caudal artery strips. The Ca contents of two components are linear functions of the Ca-ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid concentration and desaturate at rapid rates. They correspond to the extracellular and cytoplasmic spaces. A significantly smaller component releases Ca at comparatively slower rates. /sup 45/Ca uptake by the slow component consists of an ATP-dependent and an ATP-independent fraction. The /sup 45/Ca content of the ATP-dependent fraction is a function of the free Ca concentration and is independent of the Ca-ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid concentration. Its content was enhanced by oxalate and was abolished by Triton X-100 skinning solutions. The ATP-independent component was not affected by Triton X-100 skinning and may represent Ca binding to cytoplasmic molecules and structures. The sequestered Ca was released with caffeine or Ca but not by epinephrine. The observations indicate that the sarcoplasmic reticulum and mitochondria of vascular smooth muscle strips skinned with saponin retain their functional integrity after saponin skinning.« less

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain.

PubMed

Victory, R A; Gajraj, N M; Van Elstraete, A; Pace, N A; Johnson, E R; White, P F

1995-05-01

To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. A prospective, randomized, double-blind study. University medical center. 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg i.v., droperidol 50 micrograms/kg i.v., and sufentanil 0.5 microgram/kg i.v. and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 microgram/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye.

PubMed

Ichien, K; Yamamoto, T; Kitazawa, Y; Oguri, A; Ando, H; Kondo, Y

1997-01-01

To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. A 0.1 ml solution of mitomycin C containing 0.22 microgram, 2.9 micrograms, or 28 micrograms of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps' activities and urinary excretion of natriuretic peptides.

PubMed

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; Cardoso, Flávia Magalhães; de Souza, Aloa Machado; Caruso-Neves, Celso; Cassali, Geovanni Dantas; dos Reis, Adelina Martha; Brandão, Maria das Graças Lins; Vieira, Maria Aparecida Ribeiro

2012-04-11

In a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAaD) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAPAaD- induced antidiuresis in rats. To evaluate the effect of SAPAaD on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAPAaD (SAPAaD + Furo) or 0.5 ml of 0.9 % NaCl (NaCl + Furo). In the SAPAaD + NaCl group, rats were pretreated with SAPAaD and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na(+) pumps on antidiuretic effects promoted by SAPAaD, rats were given the physiological solution (as above) containing SAPAaD (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na(+)- and (Na(+),K(+))-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively. It was observed that SAPAaD inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p < 0.05), increased both Na(+)-ATPase (from 25.0 ± 5.9 nmol Pi.mg(-1).min(-1), control, to 52.7 ± 8.9 nmol Pi.mg(-1).min(-1), p < 0.05) and (Na(+),K(+))-ATPase (from 47.8 ± 13.3 nmol Pi.mg(-1).min(-1), control, to 79.8 ± 6.9 nmol Pi .mg(-1).min(-1), p < 0.05) activities in the renal cortex. SAPAaD also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP. We concluded that the SAPAaD antidiuretic effect may be due to an increase in the renal activities of Na(+)- and (Na(+),K(+))-ATPases and/or a decrease in the renal ANP.

Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.

PubMed

Wojciechowski, Kamil; Orczyk, Marta; Gutberlet, Thomas; Geue, Thomas

2016-02-01

The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. The oleanolic acid-type saponins (α-hederin and hederacoside C) were shown to form 1:1 complexes with lipids in bulk, characterized by stability constants in the range (4.0±0.2)·10(3)-(5.0±0.4)·10(4) M(-1). The complexes with cholesterol are generally stronger than those with DPPC. On the contrary, ammonium glycyrrhizate does not form complexes with any of the lipids in solution. The saponin-lipid interactions were also studied in a confined environment of Langmuir monolayers of DPPC and DPPC/cholesterol with the saponins present in the subphase. A combined monolayer relaxation, surface dilational rheology, fluorescence microscopy and neutron reflectivity (NR) study showed that all three saponins are able to penetrate pure DPPC and mixed DPPC/cholesterol monolayers. Overall, the effect of the saponins on the model lipid monolayers does not fully correlate with the lipid-saponin complex formation in the homogeneous solution. The best correlation was found for α-hederin, for which even the preference for cholesterol over DPPC observed in bulk is well reflected in the monolayer studies and the literature data on its membranolytic activity. Similarly, the lack of interaction of ammonium glycyrrhizate with both lipids is evident equally in bulk and monolayer experiments, as well as in its weak membranolytic activity. The combined bulk and monolayer results are discussed in view of the role of confinement in modulating the saponin-lipid interactions and possible mechanism of membranolytic activity of saponins. Copyright © 2015 Elsevier B.V. All rights reserved.

Alfalfa (Medicago sativa L.) shoot saponins: identification and bio-activity by the assessment of aphid feeding.

PubMed

Mazahery-Laghab, H; Yazdi-Samadi, B; Bagheri, M; Bagheri, A R

2011-01-01

Biochemical components in alfalfa (Medicago sativa L.), such as saponins, can act as protecting factors against bio-stresses. Saponins are also antifeedants and show oral toxicity towards higher and lower animals. Changes in saponins, such as variation in the carbon skeleton, or hydrolysis of saponin glycosides and other conjugates, may change their biological effects. The aims of this research were to study saponin variation in different growth stages of alfalfa and to investigate the biological role of saponins in the spotted alfalfa aphid, Therioaphis maculata. Saponins from alfalfa shoots in different growth stages were extracted, chemically purified and analysed by TLC. Specific saponins such as soyasaponin1 from root and shoot and two bisdesmosides of medicagenic acid, one from shoot and another from root tissues, were identified using reference compounds allowing changes in saponin composition during plant development in different shoot tissues of alfalfa to be assessed. The response of the alfalfa aphid to feeding on alfalfa in different growth stages was studied. No significant difference in the survival of aphids, from neonate to adult, was observed, but due to the antibiotic effects of saponins, two differences were found in the onset of nymph production and cumulative nymph production. The results show that the saponin composition in alfalfa changes with plant development and this, in turn, can often negatively affect the development of specific insect pests such as the spotted alfalfa aphid, suggesting a possible biological role of alfalfa saponins.

Adsorption of saponin compound in Carica papaya leaves extract using weakly basic ion exchanger resin

NASA Astrophysics Data System (ADS)

Abidin, Noraziani Zainal; Janam, Anathasia; Zubairi, Saiful Irwan

2016-11-01

Adsorption of saponin compound in papaya leaves juice extract using Amberlite® IRA-67 resin was not reported in previous studies. In this research, Amberlite® IRA-67 was used to determine the amount of saponin that can be adsorbed using different weights of dry resin (0.1 g and 0.5 g). Peleg model was used to determine the maximum yield of saponin (43.67 mg) and the exhaustive time (5.7 days) prior to a preliminary resin-saponin adsorption study. After adsorption process, there was no significant difference (p>0.05) in total saponin content (mg) for sample treated with 0.1 g (3.79 ± 0.55 mg) and sample treated with 0.5 g (3.43 ± 0.51 mg) dry weight resin. Long-term kinetic adsorption of resin-saponin method (>24 hours) should be conducted to obtain optimum freed saponin extract. Besides that, sample treated with 0.1 g dry weight resin had high free radical scavenging value of 50.33 ± 2.74% compared to sample treated with 0.5 g dry weight resin that had low free radical scavenging value of 24.54 ± 1.66% dry weights. Total saponin content (mg), total phenolic content (mg GAE) and free radical scavenging activity (%) was investigated to determine the interaction of those compounds with Amberlite® IRA-67. The RP-HPLC analysis using ursolic acid as standard at 203 nm showed no peak even though ursolic acid was one of the saponin components that was ubiquitous in plant kingdom. The absence of peak was due to weak solubility of ursolic acid in water and since it was only soluble in solvent with moderate polarity. The Pearson's correlation coefficient for total saponin content (mg) versus total phenolic content (mg GAE) and radical scavenging activity (%) were +0.959 and +0.807. Positive values showed that whenever there was an increase in saponin content (mg), the phenolic content (mg GAE) and radical scavenging activity (%) would also increase. However, as the resin-saponin adsorption was carried out, there was a significant decrease of radical scavenging activity (%) as the amount of the resin increased. Moreover, the saponin amount did not show any reduction as the amount of resin resin increased. Therefore, there was other active ingredient which has the antioxidant properties were affected by the adsoprtion process. For that reason, the kinetic equilibrium of resin-saponin adsorption studies against the ratio of resin-to-extract has to be carried out to determine the efficacy of the extract therapeutic properties prior to the cell culture studies.

Cytotoxic triterpenoid saponins from husks of Aesculus californica (Spach) Nutt.

PubMed

Yuan, Wei; Wang, Ping; Su, Zushang; Wang, Victoria S; Li, Shiyou

2013-06-01

Fifteen polyhydroxyoleanene saponins, aesculiosides C1-C15 (1-15), were isolated from husks of Aesculus californica. Their structures were established by extensive spectroscopic and chemical analyses. The triterpenoid saponins from A. californica have greater structural diversity than those from any other investigated species thus far in the genus Aesculus. The chemotaxonomic characteristic of aesculiosides C1-C15 is that the unit attached to the C-3 of the aglycone is a glucopyranosyl moiety, instead of a glucuronopyranosyl group in the saponins that have been isolated from other Aesculus species. The saponins isolated from A. californica then provide important evolutionary and chemotaxonomic knowledge of the Aesculus genus, a well-known intercontinental disjunct genus in the Northern hemisphere. Aesculiosides C1-C15 (1-15) showed cytotoxicity to human non-small cell lung tumor (A549) with GI50 ranged from 3.76 to >25μM. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of intramolecular hydrogen bonds on regioselectivity of glycosylation. Synthesis of lupane-type saponins bearing the OSW-1 saponin disaccharide unit and its isomers.

PubMed

Kuczynska, Kinga; Cmoch, Piotr; Rárová, Lucie; Oklešťková, Jana; Korda, Anna; Pakulski, Zbigniew; Strnad, Miroslav

2016-03-24

A series of lupane-type saponins bearing OSW-1 disaccharide unit as well as its regio- and stereoisomers were prepared and used for the structure-activity relationships (SAR) study. Unexpected preference for 1→4-linked regioisomers and an unusual inversion of the conformation of the sugar rings were noted. Cytotoxic activity of new lupane compounds was evaluated in vitro and revealed that some saponins exhibited an interesting bioactivity profile against human cancer cell lines. Influence of the protecting groups on the cytotoxicity was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Foam Properties and Detergent Abilities of the Saponins from Camellia oleifera

PubMed Central

Chen, Yu-Fen; Yang, Chao-Hsun; Chang, Ming-Shiang; Ciou, Yong-Ping; Huang, Yu-Chun

2010-01-01

The defatted seed meal of Camellia oleifera has been used as a natural detergent and its extract is commercially utilized as a foam-stabilizing and emulsifying agent. The goal of this study was to investigate the foam properties and detergent ability of the saponins from the defatted seed meal of C. oleifera. The crude saponin content in the defatted seed meal of C. oleifera was 8.34 and the total saponins content in the crude saponins extract was 39.5% (w/w). The foaming power of the 0.5 crude saponins extract solution from defatted seed meal of C. oleifera was 37.1 of 0.5 SLS solution and 51.3% to that of 0.5% Tween 80 solution. The R5 value of 86.0% represents good foam stability of the crude saponins extracted from the defatted seed meal of the plant. With the reduction of water surface tension from 72 mN/m to 50.0 mN/m, the 0.5% crude saponins extract solution has wetting ability. The sebum-removal experiment indicated that the crude saponins extract has moderate detergency. The detergent abilities of the saponins from C. oleifera and Sapindus mukorossi were also compared. PMID:21151446

Determination of flavonoids and saponins in Gynostemma pentaphyllum (Thunb.) Makino by liquid chromatography-mass spectrometry.

PubMed

Kao, T H; Huang, S C; Inbaraj, B Stephen; Chen, B H

2008-09-26

Gynostemma pentaphyllum (Thunb.) Makino, a traditional Chinese herb possessing antitumor and antioxidant activities, has been shown to contain several functional components like saponins and flavonoids. However, their identities remain uncertain. The objectives of this study were to develop an appropriate extraction, purification and HPLC-MS method to determine saponins and flavonoids in G. pentaphyllum. Both flavonoids and saponins were extracted with methanol, followed by purification with a C18 cartridge to elute the former with 50% methanol and the latter with 100% methanol. A total of 34 saponins were separated within 40 min by a Gemini C18 column and a gradient mobile phase of acetonitrile and 0.1% formic acid in water, in which 18 saponins were identified by LC-MS with ESI mode and Q-TOF (LC/MS/MS). Similarly, a total of eight flavonoids were separated within 45 min by the same column and a gradient solvent system of methanol and 0.1% formic acid in water, with identification being carried out by a post-column derivatization method and LC-MS with ESI mode. The amounts of flavonoids in G. pentaphyllum ranged from 170.7 to 2416.5 mug g(-1), whereas saponins were from 491.0 to 89,888.9 mug g(-1).

Cytotoxic triterpenoid saponins from the rhizomes of Anemone taipaiensis.

PubMed

Wang, Xiao-Yang; Chen, Xiao-Li; Tang, Hai-Feng; Gao, Hui; Tian, Xiang-Rong; Zhang, Ping-Hu

2011-09-01

Two new oleanane-type triterpenoid saponins, 1 and 2, and a new natural product, 3, together with five known saponins, 4- 8, were isolated from the rhizomes of ANEMONE TAIPAIENSIS. Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Six saponins, 1, 2, 4- 7, which possessed a free carboxylic group at C-28, exhibited significant cytotoxicity against human leukemia HL-60 cells and human hepatocellular carcinoma Hep-G2 cells with IC (50) values in the range of 1.31-10.12 µM. © Georg Thieme Verlag KG Stuttgart · New York.

Assessment of Antioxidant and Cytotoxicity Activities of Saponin and Crude Extracts of Chlorophytum borivilianum

PubMed Central

Abd Aziz, Maheran; Stanslas, Johnson; Abdul Kadir, Mihdzar

2013-01-01

The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and β-carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL−1), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL−1). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line. PMID:24223502

Characterization and Quantitation of Triterpenoid Saponins in Raw and Sprouted Chenopodium berlandieri spp. (Huauzontle) Grains Subjected to Germination with or without Selenium Stress Conditions.

PubMed

Lazo-Vélez, Marco A; Guajardo-Flores, Daniel; Mata-Ramírez, Daniel; Gutiérrez-Uribe, Janet A; Serna-Saldivar, Sergio O

2016-01-01

Pseudocereal Chenopodium berlandieri spp. (huauzontle) was evaluated to determine saponin composition. Saponins were evaluated in raw and germinated grains subjected to chemical stress induced by sodium selenite. Analysis by liquid chromatography coupled with ELSD detector revealed the presence of 12 saponins, identified according to compounds previously assayed in Chenopodium quinoa. Saponins found at the highest concentrations in raw grains were derived from oleanolic and phytolaccagenic acids. Total saponin concentration significantly decreased in germinated compared to raw grains due to the significant loss of 90.1% and 95.7% of the phytolaccagenic acid without and with chemical selenium stress, respectively. The most abundant saponin in germinated sprouts decreased during normal germination. Interestingly, the concentration of this particular saponin significantly increased during the Se-induced stress germination. Chemical stress with selenium salts proved to change the saponin composition in geminated Chenopodium berlandieri spp. grains, therefore affecting their potential use as ingredient in the food industry. © 2015 Institute of Food Technologists®

Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape

NASA Technical Reports Server (NTRS)

Sims, J. R.; Karp, S.; Ingber, D. E.

1992-01-01

Studies were carried out with capillary endothelial cells cultured on fibronectin (FN)-coated dishes in order to analyze the mechanism of cell and nuclear shape control by extracellular matrix (ECM). To examine the role of the cytoskeleton in shape determination independent of changes in transmembrane osmotic pressure, membranes of adherent cells were permeabilized with saponin (25 micrograms/ml) using a buffer that maintains the functional integrity of contractile microfilaments. Real-time videomicroscopic studies revealed that addition of 250 microM ATP resulted in time-dependent retraction and rounding of permeabilized cells and nuclei in a manner similar to that observed in intact living cells following detachment using trypsin-EDTA. Computerized image analysis confirmed that permeabilized cells remained essentially rigid in the absence of ATP and that retraction was stimulated in a dose-dependent manner as the concentration of ATP was raised from 10 to 250 microM. Maximal rounding occurred by 30 min with projected cell and nuclear areas being reduced by 69 and 41%, respectively. ATP-induced rounding was also accompanied by a redistribution of microfilaments resulting in formation of a dense net of F-actin surrounding retracted nuclei. Importantly, ATP-stimulated changes in cell, cytoskeletal, and nuclear form were prevented in permeabilized cells using a synthetic myosin peptide (IRICRKG) that has been previously shown to inhibit actomyosin filament sliding in muscle. In contrast, both the rate and extent of cell and nuclear rounding were increased in permeabilized cells exposed to ATP when the soluble FN peptide, GRGDSP, was used to dislodge immobilized FN from cell surface integrin receptors.(ABSTRACT TRUNCATED AT 250 WORDS).

Aqueous extracts from asparagus stems prevent memory impairments in scopolamine-treated mice.

PubMed

Sui, Zifang; Qi, Ce; Huang, Yunxiang; Ma, Shufeng; Wang, Xinguo; Le, Guowei; Sun, Jin

2017-04-19

Aqueous extracts from Asparagus officinalis L. stems (AEAS) are rich in polysaccharides, gamma-amino butyric acid (GABA), and steroidal saponin. This study was designed to investigate the effects of AEAS on learning, memory, and acetylcholinesterase-related activity in a scopolamine-induced model of amnesia. Sixty ICR mice were randomly divided into 6 groups (n = 10) including the control group (CT), scopolamine group (SC), donepezil group (DON), low, medium, and high dose groups of AEAS (LS, MS, HS; 1.6 mL kg -1 , 8 mL kg -1 , 16 mL kg -1 ). The results showed that 8 mL kg -1 of AEAS used in this study significantly reversed scopolamine-induced cognitive impairments in mice in the novel object recognition test (P < 0.05) and the Y-maze test (P < 0.05), and also improved the latency to escape in the Morris water maze test (P < 0.05). Moreover, it significantly increased acetylcholine and inhibited acetylcholinesterase activity in the hippocampus, which was directly related to the reduction in learning and memory impairments. It also reversed scopolamine-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) and the cAMP response element-binding protein (CREB) mRNA expression. AEAS protected against scopolamine-induced memory deficits. In conclusion, AEAS protected learning and memory function in mice by enhancing the activity of the cholinergic nervous system, and increasing BDNF and CREB expression. This suggests that AEAS has the potential to prevent cognitive impairments in age-related diseases, such as Alzheimer's disease.

Effect of ginseng saponins on the recombinant serotonin type 3A receptor expressed in xenopus oocytes: implication of possible application as an antiemetic.

PubMed

Min, Kyeong T; Koo, Bon N; Kang, Jeong W; Bai, Sun Joon; Ko, Sung R; Cho, Zang-Hee

2003-08-01

Nausea and vomiting are the most frequently reported side-effects by patients who are given general anesthesia perioperatively and patients with cancer who undergo chemotherapy or radiotherapy. Serotonin (5-hydroxytryptamine, 5HT) type 3A receptor (5HT(3A) receptor) is known to mediate nausea and vomiting and its antagonists have been used effectively to prevent and/or reduce the incidence and severity of nausea and vomiting. However, the adverse effects on cardiac function, such as QT interval prolongation, limit their routine use by these patients. This study was designed to elucidate the effect of ginseng saponins on the recombinant 5HT(3A) receptor expressed in the xenopus oocyte. After in vitro transcription of the recombinant human 5HT(3A) receptor in the Xenopus laevis oocyte, we examined Panax ginseng saponins (total saponin [TS], panaxadiol saponin [PD] fraction, panaxatriol saponin [PT] fraction, and ginsenoside-Rb1 and -Rg1) for their ability to inhibit current flow through the 5HT(3A) receptor using the voltage-clamp technique. All saponin fractions (TS, PD, PT fraction, as well as ginsenoside-Rb1 and -Rg1) inhibited the peak current induced by the agonist 5HT on the 5HT(3A) receptor in a concentration-dependent, reversible, and voltage-independent manner. The PT fraction inhibited 5HT-induced currents in 5HT(3A) receptor more than the PD fraction; meanwhile, there was a similar degree of inhibition between ginsenoside-Rg1 and -Rb1, the main substitutes of PT fraction and PD saponin fractions, respectively. These results indicate that ginseng saponins, especially PT fraction, have substantial inhibitory effects on the recombinant 5HT(3A) receptor, suggesting that some of the specific types of ginsenoside might have an antagonistic action against 5HT(3A) receptor related to nausea and vomiting.

Pressure-maximal coronary flow relationship in regionally stunned porcine myocardium.

PubMed

Duncker, D J; McFalls, E O; Krams, R; Verdouw, P D

1992-06-01

In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min-1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function.

Triterpenoid saponins from Polaskia chichipe Backbg. and their inhibitory or promotional effects on the melanogenesis of B16 melanoma cells.

PubMed

Fujihara, Koji; Takahashi, Kunio; Koyama, Kiyotaka; Kinoshita, Kaoru

2017-10-01

Five new oleanane-type saponins 1-5 together with a known saponin 6 and a steroidal glycoside 7 were isolated from Polaskia chichipe Backbg., and their structures were determined from their 1D and 2D NMR and HRFABMS spectral data. The six isolated saponins 1-6 were tested for their effects on the melanogenesis of B16 melanoma 4A5 cells. Compound 1 exerted an inhibitory effect at 100 μM whereas compound 3 promoted melanogenesis at the same concentration, even though these two compounds contain the same aglycon structure. The dose-dependent activities of compounds 1 and 3 on melanin synthesis were investigated.

Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity.

PubMed

Bader, D; Blondheim, O; Jonas, R; Admoni, O; Abend-Winger, M; Reich, D; Lanir, A; Tamir, A; Eldar, I; Attias, D

1996-04-01

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.

Triterpenoid saponins from Anemone flaccida induce apoptosis activity in HeLa cells.

PubMed

Han, Lin-Tao; Li, Juan; Huang, Fang; Yu, Shang-Gong; Fang, Nian-Bai

2009-01-01

Five triterpenoid saponins were isolated from Anemone flaccida Fr. Schmidt. Their structures were identified as glycoside St-I4a (1), glycoside St-J (2), anhuienoside E (3), hederasaponin B (4), and flaccidoside II (5). Compounds 1-2 were isolated from Anemone family for the first time, and compounds 3-4 were isolated from this plant for the first time. The inhibitory effects of saponins on proliferation of HeLa cells were studied by MTT assay, the apoptosis-induction activity was observed by cell-cycle analysis and caspase-3 expression assay. The antitumor activities of the saponins were ranked in the following order: 5 > 3 > 4 > 1 > 2. The data presented here indicated that naturally occurring triterpenoid saponins can be regarded as excellent structures for the potential development of new anticancer agents.

Inhibitory effect of soy saponins on the activity of β-lactamases, including New Delhi metallo-β-lactamase 1.

PubMed

Horie, Hitoshi; Chiba, Asuka; Wada, Shigeo

2018-05-01

β-Lactamase-producing bacteria encode enzymes that inactivate β-lactam antibiotics by catalyzing the hydrolysis of the β-lactam ring. Crude soy saponins were observed to have synergistic effects on the antimicrobial activity of β-lactam antibiotics against β-lactamase-producing Staphylococcus aureus strains. Furthermore, the activities of β-lactamases derived from Enterobacter cloacae , Escherichia coli , and S. aureus were decreased significantly in the presence of crude soy saponins. This inhibitory effect was also observed against the New Delhi metallo-β-lactamase 1 (NDM-1), an enzyme whose activity is not inhibited by the current β-lactamase inhibitors. The synergistic effect on the antimicrobial activity of β-lactam antibiotics by crude soy saponins was thought to result from the inhibition the β-lactamase activity. The components of crude soy saponins include several kinds of soyasaponins and soyasapogenols. It was revealed that soyasaponin V has the highest inhibitory activity against NDM-1. The combined use of soy saponins with β-lactam antibiotics is expected to serve as a new therapeutic modality, potentially enhancing the effectiveness of β-lactam antibiotics against infectious diseases caused by β-lactamase-producing bacteria, including those encoding NDM-1.

Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms.

PubMed

Khakimov, Bekzod; Tseng, Li Hong; Godejohann, Markus; Bak, Søren; Engelsen, Søren Balling

2016-11-24

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2-5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds.

Hemolytic and antimicrobial activities differ among saponin-rich extracts from guar, quillaja, yucca, and soybean.

PubMed

Hassan, Sherif M; Byrd, James A; Cartwright, Aubry L; Bailey, Chris A

2010-10-01

Hemolytic and antibacterial activities of eight serial concentrations ranged from 5-666 microg/mL of saponin-rich extracts from guar meal (GM), quillaja, yucca, and soybean were tested in 96-well plates and read by enzyme-linked immunosorbent assay plate-well as 650 nm. Hemolytic assay used a 1% suspension of chicken red blood cells with water and phosphate buffered saline as positive and negative controls, respectively. Antibacterial activity against Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli were evaluated using ampicillin and bacteria without saponin-rich extract as positive and negative controls, respectively. The 100% MeOH GM and commercial quillaja saponin-rich extracts were significantly the highest in both hemolytic and antibacterial activities against all bacteria at the same concentration tested. Soybean saponin-rich extract had no antibacterial activity against any of the bacteria at the concentrations tested while yucca saponin-rich extract had no antibacterial activity against the gram-negative bacteria at the concentrations tested. GM and quillaja saponin-rich extracts were hemolytic, while yucca and soybean saponin-rich extracts were not hemolytic at the concentrations tested. No saponin-rich extract source had antibacterial activity against S. typhimurium or E. coli at the concentrations tested. Both GM and quillaja saponin-rich extracts exhibited antibacterial activity against S. aureus. Saponin-rich extracts from different plant sources have different hemolytic and antibacterial activities.

Sterol-recognition ability and membrane-disrupting activity of Ornithogalum saponin OSW-1 and usual 3-O-glycosyl saponins.

PubMed

Malabed, Raymond; Hanashima, Shinya; Murata, Michio; Sakurai, Kaori

2017-12-01

OSW-1 is a structurally unique steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, and has exhibited highly potent and selective cytotoxicity in tumor cell lines. This study aimed to investigate the molecular mechanism for the membrane-permeabilizing activity of OSW-1 in comparison with those of other saponins by using various spectroscopic approaches. The membrane effects and hemolytic activity of OSW-1 were markedly enhanced in the presence of membrane cholesterol. Binding affinity measurements using fluorescent cholestatrienol and solid-state NMR spectroscopy of a 3-d-cholesterol probe suggested that OSW-1 interacts with membrane cholesterol without forming large aggregates while 3-O-glycosyl saponin, digitonin, forms cholesterol-containing aggregates. The results suggest that OSW-1/cholesterol interaction is likely to cause membrane permeabilization and pore formation without destroying the whole membrane integrity, which could partly be responsible for its highly potent cell toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Microcystin in cyanobacterial blooms in a Chilean lake.

PubMed

Campos, V; Cantarero, S; Urrutia, H; Heinze, R; Wirsing, B; Neumann, U; Weckesser, J

1999-05-01

Cyanobacterial blooms dominated by Microcystis sp. occurred in lake Rocuant ("marisma", near Concepción/Chile) in February 1995 and 1996. In the bloom samples collected in both years the hepatotoxin microcystin was detected by RP-HPLC in both samples and in the sample of 1995 also by a toxicity assay using primary rat hepatocytes. In the bloom of 1995, the microcystin content of the dry bloom biomass was determined to be 130 micrograms/g on the basis of the RP-HPLC peak area and 800 micrograms/g on the basis of the rat hepatotoxicity assay, respectively. In the bloom of 1996, RP-HPLC analysis revealed a microcystin content of 8.13 micrograms/g bloom material dry weight. In this year no hepatotoxicity was measured using a concentration range up to 0.8 mg (d. w.) of bloom material per ml in the rat hepatotoxicity assay. This is the first report on the detection of microcystins in Chilean water bodies.

The influence of diltiazem and nifedipine on renal function in the rat.

PubMed Central

Johns, E. J.

1985-01-01

The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone-anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. Diltiazem was infused at 5, 10 and 20 micrograms kg-1 min-1. Blood pressure did not change following 5 micrograms kg-1 min-1 diltiazem but was significantly reduced, by 12 mmHg, after 10 micrograms kg-1 min-1 and by 17 mmHg after 20 micrograms kg-1 min-1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 micrograms kg-1 min-1 diltiazem, 20% and 24% respectively, by 10 micrograms kg-1 min-1 diltiazem, but were unchanged by 20 micrograms kg-1 min-1. Infusion of nifedipine at 0.5, 1.0 and 2.0 micrograms kg-1 min-1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 microgram kg-1 min-1 only, while g.f.r. did not change at any dose. Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 microgram kg-1 min-1 nifedipine, 127%, 197% and 194% respectively, by 1.0 microgram kg-1 min-1, while these variables remained unchanged by a dose of 2.0 micrograms kg-1 min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3986432

Passive participation of fixed platelets in aggregation facilitated by covalently bound fibrinogen.

PubMed

Agam, G; Livne, A

1983-01-01

The role of fibrinogen in interplatelet recognition during aggregation was examined by combining two cell types: fresh platelets (in limiting density) activated by thrombin or A23187, and formaldehyde-fixed platelets, bearing cross-linked fibrinogen. The fixed platelets did not aggregate by themselves, nor with resting platelets, but were capable of interacting with activated platelets and of participating passively in aggregation. The participation, expressed by enhanced aggregation, was assayed by the conventional turbidometric traces and by cosedimentation of fixed 3H-platelets with aggregates of fresh platelets. Platelet suspensions, prepared without special means to avert spontaneous activation, retained plasma fibrinogen to the extent of 50 micrograms/ml of a suspension containing 10(8) platelets, and the derived fixed platelets participated in aggregation, independently of added fibrinogen. The capability of such fixed platelets to participate in aggregation was sensitive to proteolytic digestion and to massive acetylation. When platelet separation was aided by apyrase or aspirin, PGE1 and gel filtration, the residual plasma fibrinogen was limited to 0.4 micrograms/ml of 10(8) platelet suspension. The derived fixed platelets were incapable of participating in aggregation unless fibrinogen was added prior to fixation. The affixed fibrinogen could not be replaced by soluble fibrinogen or affixed albumin. It is concluded that fibrinogen, which binds to platelets upon activation or is linked to them covalently, is a recognition site for platelet-platelet interaction during aggregation.

Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

PubMed

Ahn, H J; Kim, K M; Kim, C K

1998-07-01

To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

[Evaluation of the usefulness of the agglutination test with Mangifera indica extract for the identification of pathogenic Yersinia enterocolitica strains].

PubMed

Kałuzewski, S; Gierczyński, R; Szych, J; Jagielski, M

1997-01-01

The study was performed on 137 Y. enterocolitica strains belonging to various serological groups, including 75 03 group strains isolated form human clinical material. The agglutination test on slides was carried out on this strains using Mangifera indica extract of own production. Agglutinating preparation obtained from the seeds of M. indica agglutinated Y. enterocolitica organisms possessing the pVY plasmid and CRMOX+ phenotype in dilutions to 1.56 micrograms/ml. In identification tests conducted parallelly agglutination solution was used in concentrations of 100 and 10 micrograms/ml. All clones of Y. enterocolitica from O3 group from cultures at 37 degrees C and with CRMOX+ phenotype possessing the pVY plasmid were agglutinated by the extract. Agglutination failed to develop in the cultures of these clones incubated at 25 degrees C. Yersinia clones not containing the pVY plasmid with CRMOX- phenotype were resistant to agglutination. The virulence plasmid was found in 44 out of 75 strains of Y. enterocolitica O3 and was identified by restriction analysis after plasmid DNA digestion with Eco RI enzyme. The obtained results agreed with those of Wauters et al. in 1995 and confirmed the opinion of these authors on the usefulness of the test with M. indica agglutinin for the identification of virulent Y. enterocolitica strains.

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

PubMed

De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

2000-05-01

To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine.

PubMed

Rudaz, S; Veuthey, J L; Desiderio, C; Fanali, S

1999-06-18

Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol and its six phase I metabolites using carboxymethylated beta-cyclodextrin (CMB) added to the background electrolyte (BGE). Baseline resolution of tramadol and its metabolites was obtained in less than 30 min using a 50 mM phosphate buffer (pH 2.5) containing 5 mM of CMB. Chiral determinations of tramadol and its main three metabolites, O-demethyltramadol (M1), N-demethyltramadol (M2) and O-demethyl-N-demethyltramadol (M5), were performed in urine after a simple double liquid-liquid extraction of 200 microliters of biological material. In the tested concentration range (0.5-20 micrograms/ml, except for M2: 0.5-10 micrograms/ml) coefficients of correlation superior than 0.994 were obtained. Within-day variation determined on three different concentrations for each enantiomers showed accuracies ranging from 95.4% to 103.2%. The relative standard deviation (RSD) of these assays was determined to be less than 10.0%. Day-to-day variation presented accuracies ranging from 96.3% to 106.5% with a RSD less than 9.0%. After oral administration of 100 mg of tramadol hydrochloride to an healthy volunteer, the urinary excretion was monitored during 30 h. About 15% of the dose was excreted as unchanged tramadol. The enantiomeric ratios of all the excreted analytes, T, M1, M2 and M5, were found to be very different to 1.0, showing that a stereoselective metabolism of tramadol clearly occurred.

[Development of arbekacin and synthesis of new derivatives stable to enzymatic modifications by methicillin-resistant Staphylococcus aureus].

PubMed

Kondo, S

1994-06-01

Our studies on the resistance mechanisms and chemical modifications of aminoglycoside antibiotics led to the synthesis of arbekacin (ABK), which was refractory to most aminoglycoside-modifying enzymes in resistant bacteria. In 1990, ABK was launched into clinical uses in Japan as a chemotherapeutic agent for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). By 1993 only a few MRSA strains moderately resistant to ABK (MIC, 6.25-12.5 micrograms/ml) had clinically been isolated. ABK was modified by the reaction with an excess of an enzyme preparation extracted from an ABK-resistant strain (12.5 micrograms/ml) and three inactivated products were produced, consisting mainly of ABK 2''-phosphate along with small amounts of 6'-N-acetyl-ABK and the doubly modified ABK. Based on these results, replacement of the 2''-hydroxyl by amino group in dibekacin (DKB) or in ABK was designed to obtain potent active derivatives against MRSA. Conversion of the 2''-hydroxyl group by DMSO-DCC oxidation followed by reductive amination with NH4OAc-NaBH3CN gave 2''-amino-2''-deoxy-DKB (D1) and -ABK (A1). Their 5-deoxy (D2 and A2), 5-epifluoro (D3 and A3) and 5-epiamino (D4 and A4) derivatives were also synthesized. All 2''-amino-2''-deoxy-ABK derivatives (A1, A2, A3 and A4) showed excellent activities against MRSA and Gram-negative bacteria, as expected. Among them, A4 having low acute toxicity and nephrotoxicity was selected as a new candidate for anti-MRSA agent.

Steroidal Saponins

NASA Astrophysics Data System (ADS)

Sahu, N. P.; Banerjee, S.; Mondal, N. B.; Mandal, D.

The medicinal activities of plants are generally due to the secondary metabolites (1) which often occur as glycosides of steroids, terpenoids, phenols etc. Saponins are a group of naturally occurring plant glycosides, characterized by their strong foam-forming properties in aqueous solution. The cardiac glycosides also possess this, property but are classified separately because of their specific biological activity. Unlike the cardiac glycosides, saponins generally do not affect the heart. These are classified as steroid or triterpenoid saponins depending on the nature of the aglycone. Steroidal glycosides are naturally occurring sugar conjugates of C27 steroidal compounds. The aglycone of a steroid saponin is usually a spirostanol or a furostanol. The glycone parts of these compounds are mostly oligosaccharides, arranged either in a linear or branched fashion, attached to hydroxyl groups through an acetal linkage (2, 3). Another class of saponins, the basic steroid saponins, contain nitrogen analogues of steroid sapogenins as aglycones.

A new saponin from Acanthopanax koreanum with anti-inflammatory activity.

PubMed

Dat, Le Duc; Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Tai, Bui Huu; Woo, Mi Hee; Manzoor, Zahid; Ali, Irshad; Koh, Young Sang; Kim, Young Ho

2017-03-01

Twelve saponins were isolated from the leaves of Acanthopanax koreanum, including one new lupane-type triterpene glycoside, named acankoreoside R (1), together with 11 known triterpenoid saponins (2-12). Their structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR), mass spectroscopic data (MS). All of the fractions and isolated saponins were evaluated for anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) by ELISA. Among them, compounds 1-5, 7, 10, and 12 showed strong inhibitions towards interleukin-12 (IL-12) production with IC 50 values ranging from 1.59 to 5.46 µM. Other compounds were weak or inactive toward IL-12 p40 production.

[Studies on red orpiment induction of NB4 and HL-60 cell apoptosis].

PubMed

Bai, Y; Huang, S

1998-09-01

To study the possible mechanism of red orpiment, which is main component of composite indigo naturalis tablets, in the treatment of acute promyelocytic leukemia(APL). The effect of red orpiment on induction of APL cell line NB4 and HL-60 apoptosis were studied by cell morphology, DNA gel electrophoresis and flow cytometry assay. Red orpiment induced NB4 and HL-60 cell apoptosis. When treated with different concentration of red orpiment(25-200 micrograms/ml) for 16 hours, both NB4 and HL-60 cells showed typical apoptosis features. If decreased the concentration of red orpiment to 12.5 micrograms/ml, the NB4 cell still showed apoptosis features while the HL-60 cell did not when cultured for 72 hours. Arsenic disulfide(As2S2) had the same effect as red orpiment did under the same experiment condition. It is the main component, As2S2 of the red orpiment that can induces NB4 and HL-60 cell apoptosis. and the red orpiment is responsible for the high CR rate of APL induced by the composite indigo naturalis tablets.

The bHLH Transcription Factors TSAR1 and TSAR2 Regulate Triterpene Saponin Biosynthesis in Medicago truncatula.

PubMed

Mertens, Jan; Pollier, Jacob; Vanden Bossche, Robin; Lopez-Vidriero, Irene; Franco-Zorrilla, José Manuel; Goossens, Alain

2016-01-01

Plants respond to stresses by producing a broad spectrum of bioactive specialized metabolites. Hormonal elicitors, such as jasmonates, trigger a complex signaling circuit leading to the concerted activation of specific metabolic pathways. However, for many specialized metabolic pathways, the transcription factors involved remain unknown. Here, we report on two homologous jasmonate-inducible transcription factors of the basic helix-loop-helix family, TRITERPENE SAPONIN BIOSYNTHESIS ACTIVATING REGULATOR1 (TSAR1) and TSAR2, which direct triterpene saponin biosynthesis in Medicago truncatula. TSAR1 and TSAR2 are coregulated with and transactivate the genes encoding 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE1 (HMGR1) and MAKIBISHI1, the rate-limiting enzyme for triterpene biosynthesis and an E3 ubiquitin ligase that controls HMGR1 levels, respectively. Transactivation is mediated by direct binding of TSARs to the N-box in the promoter of HMGR1. In transient expression assays in tobacco (Nicotiana tabacum) protoplasts, TSAR1 and TSAR2 exhibit different patterns of transactivation of downstream triterpene saponin biosynthetic genes, hinting at distinct functionalities within the regulation of the pathway. Correspondingly, overexpression of TSAR1 or TSAR2 in M. truncatula hairy roots resulted in elevated transcript levels of known triterpene saponin biosynthetic genes and strongly increased the accumulation of triterpene saponins. TSAR2 overexpression specifically boosted hemolytic saponin biosynthesis, whereas TSAR1 overexpression primarily stimulated nonhemolytic soyasaponin biosynthesis. Both TSARs also activated all genes of the precursor mevalonate pathway but did not affect sterol biosynthetic genes, pointing to their specific role as regulators of specialized triterpene metabolism in M. truncatula. © 2016 American Society of Plant Biologists. All Rights Reserved.

Efficacy evaluation of a Chinese bitter tea (Ilex latifolia Thunb.) via analyses of its main components.

PubMed

Hu, Ting; He, Xiao-Wei; Jiang, Jian-Guo; Xu, Xi-Lin

2014-05-01

In order to evaluate the health effects of Ilex latifolia Thunb., a Chinese bitter tea widely consumed as a health beverage, flavonoids, saponins, polysaccharides and alkaloids were extracted from its leaves and their in vitro antioxidant activity, anticomplement system activity, antiproliferative effects against human cervical carcinoma Hela cells, and anti-inflammatory effects against mouse macrophage RAW 264.7 cells were analyzed. Results showed that the polysaccharides exhibited a considerable inhibition of the complement system, the hemolysis inhibition rate reached 98% at a concentration of 0.8 mg mL(-1), which was clearly higher than that of the positive control (heparin sodium). The total flavonoids displayed significant DPPH scavenging activity and an inhibition effect on the generation of NO in LPS-induced RAW 264.7 macrophages. In addition, the total saponins showed a better antiproliferative effect against Hela cells, and the total alkaloids exhibited a high reducing power. It is obvious that I. latifolia has a variety of nutritional and health functions which are attributed to its different components. The analysis method presented in this research can suggest lessons for analysis of other plant foods.

Chemical characteristics of saponins from Paris fargesii var. brevipetala and cytotoxic activity of its main ingredient, paris saponin H.

PubMed

Wen, Feiyan; Yin, Hongxiang; Chen, Chu; Liu, Xianbo; Xue, Dan; Chen, Tiezhu; He, Jun; Zhang, Hao

2012-06-01

More attention was paid to the anti-tumor activity of Rhizoma Paridis (RP) recently, of which the wild resource was decreased significantly. This study was aimed to elucidate the chemical characteristics of Paris fargesii var. brevipetala (PFB) that may be administrated as alternate resource of legal RP. A HPLC-ELSD method was established to characterize the steroid saponins in rhizomes of PFB and two legal Paris species [Paris polyphylla var. chinensis (PPC) and P. polyphylla var. yunnanensis (PPY)] in Chinese Pharmacopoeia (CP). Ten saponins (paris saponins I, II, V, VI, VII, H, gracillin and other three paris saponins) were involved as standards. The results indicated that PFB contained pennogenyl saponins as the main components with small amounts of diosgenin saponins. The total contents of the detected saponins in PFB ranged from 9.12mg/g to 85.33mg/g. Nine of the twelve PFB samples own a total content of paris saponins I, II, VI, and VII more than 6.0mg/g (meeting the standard of CP 2010 edition). Principal Component Analysis (PCA) and Partial Least Squares-Discriminate Analysis (PLS-DA) both confirmed the fact that saponin profiles of PFB, PPC and PPY were different from each other. In addition, paris saponin H (Ps H), the predominant saponin of PFB (>50%), was tested in vitro to evaluate its cytotoxic activities on HepG2, A549, RPE and L929 cells with a positive control of Cisplatin. Ps H showed a remarkable cytotoxic activity on A549 cells with an IC(50) value of 1.53±0.08μg/mL. Copyright © 2012 Elsevier B.V. All rights reserved.

Determination of Parameters for Development of a Physiologically Based Model for the Toxicokinetics of C(+)P(+)-Soman

DTIC Science & Technology

1993-06-01

In conducting research utilizing recombinant DNA technology , the investigator(s) adhered to current guidelines promulgated by the National...zur Rtickstandanalyse), saponin (BDH, Poole, UK), aluminium sulfate.16 H2 0 (BDH Analar, Ž 98%), sodium bicarbonate (Lamens en Indemans, ’s...isopropanol). The mixture was extracted with 3 ml ethyl acetate. Gas chromatographic analysis of the soman stereoisomers in the ethyl acetate phase was

Automated solid-phase extraction and liquid chromatography for assay of cyclosporine in whole blood.

PubMed

Kabra, P M; Wall, J H; Dimson, P

1987-12-01

In this rapid, precise, accurate, cost-effective, automated liquid-chromatographic procedure for determining cyclosporine in whole blood, the cyclosporine is extracted from 0.5 mL of whole blood together with 300 micrograms of cyclosporin D per liter, added as internal standard, by using an Advanced Automated Sample Processing unit. The on-line solid-phase extraction is performed on an octasilane sorbent cartridge, which is interfaced with a RP-8 guard column and an octyl analytical column, packed with 5-microns packing material. Both columns are eluted with a mobile phase containing acetonitrile/methanol/water (53/20/27 by vol) at a flow rate of 1.5 mL/min and column temperature of 70 degrees C. Absolute recovery of cyclosporine exceeded 85% and the standard curve was linear to 5000 micrograms/L. Within-run and day-to-day CVs were less than 8%. Correlation between automated and manual Bond-Elut extraction methods was excellent (r = 0.987). None of 18 drugs and four steroids tested interfered.

Fluconazole penetration in cerebral parenchyma in humans at steady state.

PubMed Central

Thaler, F; Bernard, B; Tod, M; Jedynak, C P; Petitjean, O; Derome, P; Loirat, P

1995-01-01

We studied fluconazole penetration in the brain in five patients who had a deep cerebral tumor whose removal required the excision of healthy brain tissue. Plasma and brain samples were simultaneously obtained after oral ingestion of 400 mg of fluconazole daily for 4 days (90% of steady state). Fluconazole penetration in healthy cerebral parenchyma was determined. Plasma and brain samples were assayed by high-pressure liquid chromatography. Concentrations in plasma and brain tissue were 13.5 +/- 5.5 micrograms/ml and 17.6 +/- 6.6 micrograms/g, respectively. The average ratio of concentrations in the brain and plasma (four patients) was 1.33 (range, 0.70 to 2.39). Despite the lack of data concerning the penetration of fluconazole in brain abscesses, these results should permit the use of a daily dose of 400 mg of fluconazole in prospective clinical studies that evaluate the effectiveness of this drug in the treatment of brain abscesses due to susceptible species of fungi. PMID:7625804