Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antinuclear antibodies (ANA) development was studied in male guinea pigs in response to chronic treatment with procainamide, hydralazine, acetanilide or caffeine. Acetanilide and caffeine have not previously been associated with ANA induction. Fifty-one weanling Hartley guinea pigs were divided into five groups which received either procainamide, hydralazine, acetanilide, caffeine or saline sc for 55 weeks; drug dosage was 10 mg/kg initially and was increased incrementally to 40 mg/kg by 10 months except for hydralazine, which was increased to 20 mg/kg. Two weeks before initiation of treatment, 1 mg of the appropriate drug in 0.4 ml of buffered Freund's complete adjuvant (FCA-PBS) was administered intradermally. Controls received FCA-PBS only. Sera ANA were assayed at 6, 10 and 13 months. After 13 months of treatment, those sera which were ANA positive were assayed for anti-deoxyribonucleoprotein antibodies and were titered for ANA. Chi-square analyses were performed on results of the 10- and 13-month ANA screening results. ANA induction was significant at P = 0.05 only for the group receiving procainamide at both 10 and 13 months of treatment. When the cumulative results of all ANA screens were analyzed, ANA induction was significant for procainamide, acetanilide and caffeine. The test system did not prove to be promising for unambiguous identification of drugs with ANA-inducing potential, but may be useful for studies of mechanisms of ANA induction by chemicals.
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PMID:Drug-induced antinuclear antibodies in the guinea pig. 697

The motility, acrosome integrity and fertility of ram spermatozoa were examined after treatment with five compounds (caffeine, pentoxifylline, cAMP, 2-deoxyadenosine and kallikrein). Semen was extended with a Tris-based medium and frozen in pellet form. The compounds were added at various concentrations to the semen before freezing or after thawing. Motility and acrosome characteristics were assessed over a 6-h post-thaw period of incubation at 37 degrees C. Of the five compounds examined, only pentoxifylline, when added after thawing, stimulated motility but had not effect on the acrosome integrity of spermatozoa. Pregnancy rates for ewes inseminated in the uterus with semen treated after thawing with Dulbecco's phosphate-buffered saline (PBS, control) or PBS containing pentoxifylline (15 mM in the thawed semen), were 16/39 (41%) and 22/42 (52%) respectively. Motility characteristics of spermatozoa assessed by image analysis (Hamilton-Thorne analyser) were initially better after treatment of thawed semen with pentoxifylline than with PBS ("percent motility', "percent progressive motility', "percent rapid', "percent moderate' and "percent static', P < 0.01 or P < 0.001), but there was a greater deterioration in these characteristics during post-thaw incubation in semen treated with pentoxifylline than in the controls. The deterioration in motility characteristics occurred within 4 h of thawing and this may have been responsible for the modest improvement in fertility of spermatozoa treated with pentoxifylline.
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PMID:Motility, acrosome integrity and fertility of frozen ram spermatozoa treated with caffeine, pentoxifylline, cAMP, 2-deoxyadenosine and kallikrein. 884 74

In this study the recruitment of leucocytes and phagocytosis of spermatozoa after artificial insemination of multiparous sows was investigated. In Expt 1, groups of sows received either no inseminate (n = 6) or inseminates with various concentrations of spermatozoa and seminal plasma or different inseminate volumes (n = 9 per group). In Expt 2, groups of sows received inseminates containing no addition, caffeine + CaCl(2), or excess EDTA (n = 6 per group). Leucocytes and spermatozoa were counted in the collected backflow from the vulva, and in the PBS flushings of the genital tract of sows killed at 4 h after insemination. Tissue homogenates were checked for remaining spermatozoa. Leucocyte recruitment did not depend on the presence of seminal plasma or spermatozoa. In the control groups about 43% of the inseminated spermatozoa were found in the backflow and 5% in the genital tract. Many spermatozoa could be recognized inside polymorphonuclear leucocytes. With an inseminate volume of 20 ml instead of 80 ml, fewer spermatozoa were found in the backflow and more (non-phagocytosed) spermatozoa were recovered in the uterus (P < or = 0.05). With a sperm dose of 0.24 x 10(9) instead of 2.4 x 10(9), a higher percentage of the inseminated spermatozoa was recovered in the oviducts (P < or = 0.05). The use of caffeine + CaCl(2) resulted in lower recruitment of leucocytes (P < or = 0.05) and a higher number of non-phagocytosed spermatozoa in the uterus (P < or = 0.01) compared with controls. The numbers of spermatozoa in the oviducts were not different. Insemination with excess EDTA had no positive effects on the number of spermatozoa in the genital tract.
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PMID:Neutrophil recruitment and phagocytosis of boar spermatozoa after artificial insemination of sows, and the effects of inseminate volume, sperm dose and specific additives in the extender. 1261 99

Bovine oocytes, before and after maturation in culture, were stored in PBS with 2 M-(NH(4))(2)SO(4) + 0.1% dextran or 2 M-(NH(4))(2)SO(4) + 40 mM-Hepes + 0.5% dextran and were inseminated with frozen-thawed spermatozoa in BO medium with caffeine (5 mM) and heparin (10 mug/ml). The penetration rates of mature oocytes were very low (19 to 24%) and not significantly different between the two salt solutions in which the oocytes were stored for 2 to 89 days. Significantly lower (P < 0.01) penetration rates were observed in immature (7 to 8%) than in mature (20 to 21%) oocytes stored in the two solutions. The synergistic effect of caffeine and heparin was observed in the penetration rate of fresh mature oocytes but not in the stored oocytes, indicating the difficulty of assessing sperm capacitation and/or acrosome reaction of salt-stored mature bovine oocytes under the present condition. Using 0.1% protease the solubility of the zonae decreased in salt-stored but not in fresh oocytes, but there was no significant difference between the immature and mature oocytes regardless of storage in the salt solutions. It appears from these results that some alteration was induced in the nature of zona glycoprotein by ammonium sulfate solution.
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PMID:In vitro penetration of zona pellucida of salt-stored bovine oocytes before and after maturation by frozen-thawed spermatozoa. 1672 94

Frozen-thawed ejaculated stallion spermatozoa were preincubated for 3 h in BO medium containing 5 mM caffeine and then treated with 0.1 micro M calcium ionophore A23187 for 60 sec. Aliquots of the sperm suspension (final concentration 1-2 x 10(7)/ml) were added to the oocytes which had been matured in vitro for 32 h. In Experiment 1, there were 3 groups of oocytes; cumulus intact, denuded zona-intact, and zona-free. Cumulus cells were removed with 0.5% hyaluronidase and the zona pellucida with 0.1% protease. The oocytes were fixed 20 h after insemination with acetic acid:ethanol (1:3) and stained with 1% orcein. The sperm penetration rate of zona-free oocytes was 83%, whereas the sperm penetration rate was very low (1 to 3%) in the cumulus-enclosed or zona-intact oocytes. In Experiment 2, denuded zona-intact oocytes were placed in PBS supplemented with 10% fetal bovine serum 1 h before the end of in vitro maturation. The zona pellucida was micromanipulated with a metal microblade under x 100 magnification within 20 min of treatment with 0.3 M sucrose. For partial zona dissection, a slit in the zona pellucida was made. For partial zona removal, oocytes were transferred to protein-free PBS to fix the oocytes on the bottom of the Petri-dish and to remove a piece of the zona pellucida. Micromanipulated oocytes were subjected to in vitro fertilization as described above. Zona-intact and zona-free oocytes treated with sucrose solution for 20 min were used as controls. The penetration rates were 4 (2/57), 12 (7/58), 52 (31/60), and 86% (44/51) for zona-intact, partially zona dissected, partially zona removed, and zona-free oocytes, respectively. Proportions of oocytes with monospermic penetration were 100 (2/2), 57 (4/7), 58 (18/31), and 34% (15/44), respectively. In Experiment 3, sperm penetration and male pronucleus formation in the partially zona removed oocytes were examined at 2.5 to 20.0 h of insemination. Sperm penetration started 2.5 h post-insemination (22%, 11/49), and increased to 38% (21/55) at 5 h, to 46% (23/50) at 10 h, and to 56% (27/48) at 20 h. The transformation of sperm heads into male pronuclei was first observed 10 h post insemination. These results indicate that assisted fertilization techniques may be a useful tool for achieving fertilization and embryo production in vitro in horses.
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PMID:In vitro fertilization rate of horse oocytes with partially removed zonae. 1672 85

Immature equine oocytes were frozen-thawed with ethylene glycol (EG), 1,2-propanediol (PD) or glycerol (GL) in PBS and cultured to assess the rate of in vitro maturation (Experiment 1). Compact-cumulus oocyte complexes were collected from slaughterhouse ovaries and equilibrated for 10 min in the freezing medium containing 10% (V/V) cryoprotectant and 0.1 M sucrose. The 0.25-ml straws, loaded with 10 to 30 oocytes, were seeded at -6 degrees C and cooled to -35 degrees C at 0.3 degrees C/min before being plunged into liquid nitrogen. The straws were thawed rapidly in a 37 degrees C waterbath for 20 sec. The proportions of frozen-thawed oocytes reaching Metaphase II (MII) stage after in vitro maturation of 32 h were 15.8% (EG), 5.8% (PD) and 0% (GL), while 63.3% of the nonfrozen control oocytes matured in vitro. The fertilizing ability of immature and mature oocytes after freezing in EG was tested by the insemination of zona-free oocytes with stallion spermatozoa (Experiment 2). Spermatozoa were preincubated for 3 h with 5 mM caffeine, treated with 0.1 mu M ionophore A23187, and inseminated for 20 h at the concentration of 1 to 2 x 10(7)/ml with 6 to 10 oocytes in 50 mu l of Brackett and Oliphant (BO) medium. Immature oocytes (Group 1) were matured in vitro after thawing and then their zona pellucida removed using 0.5% protease. The zona of mature oocytes were removed immediately after thawing (Group 2) or maturation (nonfrozen controls). The oocytes, which had mechanically damaged plasma membrane or lost by artifact, were not examined for insemination. Significantly more control oocytes exhibited a polar body at the time of insemination (53.5%) than either frozen-thawed immature or mature oocytes (25.8 and 27.3%, respectively). Similar proportion of frozen-thawed and control oocytes were penetrated by spermatozoa (71.8 to 79.1%) and exhibited 2 or more pronuclei (73.6 to 80.8%). The mean numbers of spermatozoa per penetrated oocyte were 1.9, 3.0 and 2.5, respectively, for Groups 1 and 2 and for the control oocytes. These results indicate that immature equine oocytes mature to the MII stage in vitro following freezing and thawing in EG or PD but not in GL. Stallion spermatozoa can penetrate zona-free immature and mature oocytes following freezing/thawing in EG and form morphologically normal pronuclei.
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PMID:Cryopreservation of equine oocytes by 2-step freezing. 1672 12

1. Adenosine is a potent endogenous regulator of inflammation and tissue repair. Adenosine, which is released from injured and hypoxic tissue or in response to toxins and medications, may induce pulmonary fibrosis in mice, presumably via interaction with a specific adenosine receptor. We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2. As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3. Adenosine A(2A) receptors are expressed on rat and human hepatic stellate cell lines and adenosine A(2A) receptor occupancy promotes collagen production by these cells. Liver sections from mice treated with the hepatotoxins carbon tetrachloride (CCl(4)) (0.05 ml in oil, 50 : 50 v : v, subcutaneously) and thioacetamide (100 mg kg(-1) in PBS, intraperitoneally) released more adenosine than those from untreated mice when cultured ex vivo. 4. Adenosine A(2A) receptor-deficient, but not wild-type or A(3) receptor-deficient, mice are protected from development of hepatic fibrosis following CCl(4) or thioacetamide exposure. 5. Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl(4) or thioacetamide. 6. These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis.
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PMID:Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis. 1678 7

The plasma protein binding of drugs has been shown to have significant effects on the quantitative relationship between clinical pharmacokinetics and pharmacodynamics. In many clinical situations, measurement of the total drug concentration does not provide the needed information concerning the unbound fraction of drug in plasma, which is available for pharmacodynamic action. Therefore, the accurate determination of unbound plasma drug concentrations is important in understanding drug action. Many methodologies exist for determining the extent of plasma protein binding, but different methods produce a rather wide range of results for the same compound at the same concentration level. The solid phase microextraction (SPME) method reported in the present study attempts to eliminate many experimental variables that could lead to the lack of reproducibility, such as the variable content of organic solvent or ionic strength in plasma, pH shifts, and volume shifts. Five well-known drugs were chosen to study plasma protein binding: ibuprofen, warfarin, verapamil, propranolol, and caffeine, with high, intermediate and low binding properties. Dilution of plasma with isotonic PBS or incubation with 10% CO(2) in the atmosphere was found to compensate for changes in pH during incubation. The data obtained using these pH-controlled methods correlate well with the average values of plasma protein binding found in the literature. SPME, which uses an extraction phase that dissolves or adsorbs the drug of interest and rejects proteins, overcomes several limitations of currently available techniques and is a thermodynamically sound method, since the measurements are always performed at equilibrium. Compared to other methods, SPME offers several advantages: small sample size, short analysis time, possibility to automate, and ability to directly study complex samples.
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PMID:Determination of drug plasma protein binding by solid phase microextraction. 1679 10

We conducted this study to determine whether green tea constituents, (-)-epigallocatechin gallate (EGCG) and caffeine, affect the intestinal absorption of cholesterol (CH), fat, and other fat-soluble compounds. Ovariectomized rats with lymph cannula were infused intraduodenally with a lipid emulsion containing 14C-labeled CH (14C-CH), alpha-tocopherol (alpha TOH), triolein, and sodium taurocholate, without (control) or with EGCG, caffeine, or EGCG plus caffeine, in PBS, pH 6.5. The lymphatic total 14C-CH was significantly lowered by EGCG (21.1 +/- 2.1% dose), caffeine (27.9 +/- 1.7% dose), and EGCG plus caffeine (19.3 +/- 0.9% dose), compared with the control (32.4 +/- 1.6% dose). The lymphatic output of esterified CH also was significantly lower in rats infused with EGCG (7.9 +/- 0.7 micromol), caffeine (7.6 +/- 0.2 micromol), and EGCG plus caffeine (7.5 +/- 0.6 micromol) than rats in the control group (11.6 +/- 1.7 micromol). Also, EGCG and caffeine significantly lowered the absorption of alpha TOH, another highly hydrophobic lipid. However, the lymphatic outputs of oleic acid (exogenous fatty acid marker) and other fatty acids of endogenous origin were not affected by EGCG but were markedly lowered by caffeine and EGCG plus caffeine. Caffeine significantly lowered the amount of lymph flow, regardless of whether it was infused alone (14.2 +/- 3.9 mL) or with EGCG (18.6 +/- 2.0 mL), compared with EGCG (22.2 +/- 2.2 mL) alone and the control group (23.2 +/- 3.8 mL). The caffeine-induced decline in lymph flow was associated with the lowering of lipid absorption. The results indicate that both EGCG and caffeine inhibit lipid absorption and that the inhibitory effects of the 2 tea constituents are not synergistic but mediated by distinctly different mechanisms.
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PMID:Epigallocatechin gallate and caffeine differentially inhibit the intestinal absorption of cholesterol and fat in ovariectomized rats. 1705 2

In recent years, chemotherapy with caffeine has manifested potently high efficacy against osteosarcoma, although adverse effects have been observed. Recently, we developed a novel drug delivery system (DDS) with nonionic vesicles prepared from Span 80 which have promising physicochemical properties as an attractive possible alternative to commonly used liposomes. Herein, we demonstrated that tumor-specific caffeine-potentiated chemotherapy for murine osteosarcoma administered by a novel DDS with Span 80 nano-vesicles showed significant antitumor effects as well as limited adverse effects. The osteosarcoma cell line, LM8, was transplanted into C3H/HeJ mice which then were administered therapeutic agents. Ifosfamide (IFO) was employed as well as caffeine as an enhancer. Span 80 vesicles containing IFO and/or caffeine were freshly prepared. On days 0, 2 and 4, different combinations of the agents were administered to mice: IFO alone (direct i.v.), IFO vesicles (IV), IV+caffeine, IV+caffeine vesicles (CV), PBS alone vesicles (PV), and PBS alone as negative control (PBS i.v.). Then, the mice were sacrificed on day 7. Antitumor effects of the reagents were also analyzed in vitro. Moreover, fertility examination was performed. In vitro, a combination of IV+CV showed significant induction of apoptosis in the early phase. Tumor volumes in the IV+CV group were significantly reduced compared with the other groups. Histological analyses showed that the IV and IV+CV groups had significantly lower viable tumor areas. The IFO direct i.v. group showed a certain grade of renal injury as well as marked suppression of spermatogenesis, while the IV or IV+CV group showed no marked changes. The fertility test revealed that the male mice with IV+CV administration had normal fertility, and no malformations were detected in their progeny. This DDS model is of potential importance for clinical application in the therapy of metastatic osteosarcoma.
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PMID:Development of tumor-specific caffeine-potentiated chemotherapy using a novel drug delivery system with Span 80 nano-vesicles. 2563 2


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