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Acid Alone (acid + alone)
Selected AbstractsPhotocarcinogenesis of topical tazarotene and isotretinoin alone and in combination with valproic acid in hairless miceEXPERIMENTAL DERMATOLOGY, Issue 11 2008Catharina M. Lerche Abstract:, Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to simulated solar radiation (SSR) and whether valproic acid changes the effect of the retinoids: tazarotene and isotretinoin. The products were applied on the dorsal skin of 400 mice (five times weekly) followed by SSR (three times weekly) 3,4 h after the application. This was performed during 12 months or until death. Tumors appeared sooner in groups treated with tazarotene and isotretinoin compared with that of the group treated with valproic acid and the control group. The present study shows that valproic acid alone is not photocarcinogenic or photoprotective in hairless mice. When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly. [source] Preparation of tofu using chitosan as a coagulant for improved shelf-lifeINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2004Hong Kyoon No Summary The potential of chitosan as a coagulant in commercial tofu preparation was investigated with six chitosans of different molecular weights using various treatments. The following optimum processing conditions for tofu preparation were proposed: chitosan with a molecular weight of 28 kDa; chitosan solution type, 1% chitosan/1% acetic acid; chitosan solution to soymilk ratio, 1 : 8; coagulation temperature, 80 °C; coagulation time, 15 min. However, the sensory quality of tofu was notably improved using a 1 : 1 mixture of 1% acetic acid and 1% lactic acid instead of 1% acetic acid alone as a chitosan solvent. Tofu prepared with chitosan had lower ash and higher protein content than those of commercial products tested. In storage tests, the chitosan-tofu had a longer shelf-life, about 3 days, than tofu made with CaCl2. This added shelf-life is significant in view of the magnitude (366 000 tonnes year,1) of tofu produced from commercial tofu plants (1407 plants as of 1998) in Korea. [source] Ascorbic acid improves the antioxidant activity of European grape juices by improving the juices' ability to inhibit lipid peroxidation of human LDL in vitroINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 7 2001Anne-Katrine Landbo Antioxidant activities of red and white European grape juices towards copper induced lipid oxidation of human low-density lipoproteins (LDL) were examined in vitro. LDL lipid peroxidation was assessed spectrophotometrically by monitoring the development of conjugated lipid hydroperoxides at 234 nm. Red grape juice concentrate inhibited lipid peroxidation of LDL by prolonging the lag phase by 2.7 times relative to a control when evaluated at a total phenolic concentration of 10 ,M gallic acid equivalents (GAE). Both red grape juices tested blocked lipid peroxidation of LDL at 20 ,M GAE. White grape juice exerted prooxidant activity at 5,20 ,M GAE. The antioxidant activity, inhibition of lipid peroxidation of LDL in vitro, was correlated with the juices' levels of total phenols (r > 0.98, P < 0.01), anthocyanins (r > 0.99, P < 0.01), flavan-3-ols (r > 0.97, P < 0.05), and hydroxybenzoates (r > 0.96, P < 0.05) when the phenolic composition of each grape juices was analysed by HPLC. 5 ,M ascorbic acid alone did not exert antioxidant activity towards LDL, but combinations of 5 ,M ascorbic acid with 5 ,M GAE juice phenols eliminated the prooxidant activity of white grape juice, and significantly improved the antioxidant activities of red grape juices. [source] Enaminones in heterocyclic synthesis: A new regioselective synthesis of 2,3,6-trisubstituted pyridines, 6-substituted-3-aroylpyridines and 1,3,5-triaroylbenzenesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2002Balkis Al-Saleh 1-Substituted-3-dimethylaminopropenones 1a-d reacted with acetylacetone and with ethyl acetoacetate to yield regioselectively 2,3,6-trisubstituted pyridines. Refluxing 1a-d in acetic acid/ammonium acetate resulted in the formation of 6-substituted-3-aroylpyridines, whereas refluxing in acetic acid alone afforded 1,3,5-triaroylbenzene. [source] Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Bernd L. Fiebich Abstract Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 µm). In combination with acetylsalicylic acid (IC50 = 1.85 µm), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 µm in combination with 100 µm ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases. [source] N-methylation and N-formylation of a secondary amine drug (varenicline) in an osmotic tabletJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Kenneth C. Waterman Abstract Significant degradation of the amine-based smoking cessation drug varenicline tartrate in an early development phase osmotic, controlled-release (CR) formulation yields predominantly two products: N-methylvarenicline (NMV) and N-formylvarenicline (NFV). NMV is produced by reaction of the amine moiety with both formaldehyde and formic acid in an Eschweiler-Clarke reaction, while NFV is formed by reaction of formic acid alone with varenicline. This represents the first report of these reactions occurring on storage of solid pharmaceutical formulations. Both formaldehyde and formic acid are formed from oxidative degradation of polyethylene glycol (PEG) used in an osmotic coating through a process heavily dependent on the physical state of the PEG. When the concentration of PEG in the coating is sufficiently low, the PEG remains phase compatible with the other component of the coating (cellulose acetate) such that its degradation (and the resulting drug reactivity) is effectively eliminated. Antioxidants in the coating and oxygen scavengers in the packaging also serve to prevent the PEG degradation, and consequently provide for drug stability. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1499,1507, 2008 [source] Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancerALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010C. CARROLL Aliment Pharmacol Ther,31, 708,718 Summary Background, Folic acid has been identified as a possible agent for the chemoprevention of colorectal cancer. Aim, To assess the effectiveness of folic acid in reducing the recurrence of adenomas (precursors of colorectal cancer) among populations with a history of adenomas and the incidence of colorectal cancer within average-risk populations. Methods, Systematic review of randomized controlled trials comparing folic acid alone, or with other agents, vs. placebo. Eight databases were searched for relevant trials. Meta-analysis was performed. Results, The literature search retrieved 3785 citations. Six studies met the inclusion criteria. Meta-analysis of three studies in individuals with a history of adenomas showed no statistically significant difference in the relative risk of adenoma recurrence (RR 0.93, P = 0.27). A sensitivity analysis of the two higher quality trials changed the direction of effect (RR 1.16, P = 0.11). Meta-analysis of three trials in general populations demonstrated no statistically significant effect on the relative risk of colorectal cancer (RR 1.13, P = 0.54). In all three analyses, outcome event rates were higher in individuals receiving folic acid. Conclusion, There is no evidence that folic acid is effective in the chemoprevention of colorectal adenomas or colorectal cancer for any population. [source] Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2005A. Mahmood Background :,Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. Aim :,To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. Methods :,A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. Results :,Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. Conclusion :,Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone. [source] Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination?PEDIATRIC ANESTHESIA, Issue 1 2005FÜSUN S. BULUTCU MD Summary Background:, Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents. Methods:, In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU·kg,1 after induction of anesthesia, 30.000 KIU·kg,1 in the pump prime and 30.000 KIU·kg,1 after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg·kg,1 after induction of anesthesia, 100 mg·kg,1 in the pump prime and 100 mg·kg,1 after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded. Results:, Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 ± 18 ml·kg,1·24 h,1, aprotinin; 35 ± 16 ml·kg,1·24 h,1, tranexamic acid; 34 ± 19 ml·kg,1·24 h,1, combination; 35 ± 15 ml·kg,1·24 h,1). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 ± 11 min) compared with treatment groups 2, 3 and 4, respectively (40 ± 18, 42 ± 11, 42 ± 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups. Conclusions:, Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone. [source] Vitamin supplements and the risk for congenital anomalies other than neural tube defects,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2004Lorenzo D. Botto Abstract Randomized trials, supported by many observational studies, have shown that periconceptional use of folic acid, alone or in multivitamin supplements, is effective for the primary prevention of neural tube defects (NTDs). Whether this is true also for other congenital anomalies is a complex issue and the focus of this review. It is useful to consider the evidence not only for specific birth defects separately but, importantly, also for all birth defects combined. For the latter, the Hungarian randomized clinical trial indicated, for periconceptional multivitamin use, a reduction in the risk for all birth defects (odds ratio (OR),=,0.53, 95% confidence interval (CI),=,0.35,0.70), even after excluding NTDs (OR,=,0.53, 95% CI,=,0.38,0.75). The Atlanta population-based case-control study, the only large observational study to date on all major birth defects, also found a significant risk reduction for all birth defects (OR,=,0.80, 95% CI,=,0.69,0.93) even after excluding NTDs (OR,=,0.84, 95% CI,=,0.72,0.97). These and other studies also evaluated specific anomalies, including those of the heart, limb, and urinary tract, as well as orofacial clefts, omphalocele, and imperforate anus. For cardiovascular anomalies, two studies were negative, whereas three, including the randomized clinical trial, suggest a possible 25,50% overall risk reduction, more marked for some conotruncal and septal defects. For orofacial clefts, six of seven case-control studies suggest an apparent reduced risk, which could vary by cleft type and perhaps, according to some investigators, by pill dosage. For limb deficiencies, three case-control studies and the randomized trial estimated approximately a 50% reduced risk. For urinary tract defects, three case-control studies and the randomized trial reported reduced risks, as did one study of nonsyndromic omphalocele. All these studies examined multivitamin supplement use. With respect to folic acid alone, a reduced rate of imperforate anus was observed among folic acid users in China. We discuss key gaps in knowledge, possible avenues for future research, and counseling issues for families concerned about occurrence or recurrence of these birth defects. © 2004 Wiley-Liss, Inc. [source] Pulsed-Dye Laser and Retinoic Acid Delay Progression of Oral Squamous Cell Carcinoma: A Murine Model,THE LARYNGOSCOPE, Issue 7 2001Rahul K. Shah MD Abstract Objectives/Hypothesis This study examined the role of the pulsed-dye laser (PDL) at 585 nm coupled with retinoic acid at therapeutic (5.0 mg/kg) and nontherapeutic (0.5 mg/kg) doses to delay the progression of cancer with a two-hit approach. The existing vasculature is selectively targeted by the laser, whereas retinoic acid inhibits future angiogenesis. Study Design Randomized, prospective study in a murine model. Methods Twenty-five athymic nude mice were inoculated with oral squamous cell cancers on six flank sites and randomly divided into five groups: 1) control subjects, 2) treatment with 0.5 mg/kg retinoic acid (RA 0.5), 3) treatment with 5.0 mg/kg retinoic acid (RA 5.0), 4) treatment with RA 0.5 + PDL, and 5) treatment with RA 5.0 + PDL. The PDL groups received irradiation after inoculation. The retinoic acid was administered daily. The tumors were counted and measured for 14 days. Results The control group developed visible tumors in 50% of the inoculation sites at 3 days compared with 3 days (RA 0.5) and 4 days (RA 5.0) for the retinoic acid groups and 9 days (RA 0.5 + PDL) and 10 days (RA 5.0 + PDL) for the laser treatment groups. There was no tumor growth until day 7 in the RA 5.0 + PDL group. The tumor volume was statistically different between the treatment groups. Conclusion This study demonstrated the superiority of a single treatment with the PDL coupled with retinoic acid to delay the progression of cancer when compared with treatment with retinoic acid alone, thus introducing a novel strategy in cancer control. [source] Steroid hormones strongly support bovine articular cartilage integration in the absence of interleukin-1,ARTHRITIS & RHEUMATISM, Issue 12 2006Carsten Englert Objective Posttraumatic integration of articular cartilage at fracture sites is essential for mechanical stability of cartilage, and ruptured cartilage is a prerequisite for early osteoarthritis. This study was undertaken to investigate effects on articular cartilage integration mediated by steroid hormones, interleukin-1, (IL-1,), and combinations thereof. Methods Articular cartilage blocks were cultured in partial apposition for 2 weeks with ascorbic acid, testosterone, 17,-estradiol, and dehydroepiandrosterone (DHEA), with or without IL-1,. Mechanical integration was measured as adhesive strength, i.e., the maximum force at rupture of integrated cartilage blocks divided by the overlap area. Glycosaminoglycan content was used to study synthesized extracellular matrix. Results Culture in medium without supplements did not lead to integration (adhesive strength 0 kPa). With administration of ascorbic acid (100 ,g/ml), the median adhesive strength was 49 kPa. In comparison with ascorbic acid alone, all steroid hormones induced a strong, concentration-dependent stimulation of integration (with maximum values observed with DHEA at 3 × 10,5M, testosterone at 10,8M, and 17,-estradiol at 10,11M). For testosterone and 17,-estradiol, this was also reflected by an increase of glycosaminoglycan content. Adhesive strength was increased with IL-1, at 10 pg/ml, but not at 1 pg/ml or 100 pg/ml. In the presence of both IL-1, and sex hormones, integration of articular cartilage was reduced. Conclusion This is the first study to demonstrate that steroid hormones such as 17,-estradiol, DHEA, and testosterone stimulate articular cartilage integration. This effect is abrogated by low concentrations of IL-1,. In the absence of IL-1, or after neutralization of IL-1,, steroid hormones might be favorable adjuvant compounds to optimize cartilage integration. [source] Folinic acid protects against suppression of growth by Methotrexate in miceBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2001M. Perwaiz Iqbal Abstract The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean±SD body weight 9.64±0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post-MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes. Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8±0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one-way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short-term suppression of growth, however they could benefit from supplementation with folinic acid. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effect of bile salts, lipid, and humic acids on absorption of benzo[a]pyrene by isolated channel catfish (Ictalurus punctatus) intestine segmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2001Lynn P. Weber Abstract Dietary absorption of lipophilic contaminants may be a significant route of exposure in aquatic organisms. Bile salts, lipids, and humic acids are important factors that may influence the intestinal absorption of a contaminant such as benzo[a]pyrene (BaP). We hypothesized that bile salts, monoglycerides, and free fatty acids would increase BaP intestinal absorption, while triglycerides, humic acids, and sediment would decrease BaP intestinal absorption. We have established and validated an in vitro model to examine modification of 3H-BaP absorption in everted intestinal segments from channel catfish (Ictalurus punctatus). Uptake of BaP into the everted intestinal segments continued to increase over the times examined in this study (60 min) and apparently occurs passively; thus, fugacity-based models of uptake are supported. Absorption of BaP into intestinal cells was significantly decreased by the addition of monoglycerides and free fatty acids to bile salts in the incubation media. Addition of triglycerides decreased BaP absorption even further. Humic acids may have decreased BaP intestinal absorption, while natural sediment may have increased BaP absorption. The results of this study suggest that all lipids may decrease intestinal uptake of lipophilic contaminants if they remain in unabsorbable excess in the intestinal lumen by retaining BaP in lipid/bile micelles. In contrast, if triglycerides are hydrolyzed into monoglycerides/free fatty acids prior to absorption, lipophilic contaminant uptake will likely be facilitated. Thus, it may be the hydrolytic state of lipids that determines its effects on BaP absorption. Humic acids alone may decrease dietary uptake of BaP, but our results suggest that other components in natural sediment may counteract this effect to cause a slight enhancement of BaP uptake. Further studies are needed to determine the dietary conditions necessary for bio-accumulation to contribute significantly to lipophilic contaminant body burdens in benthivorous fish. Finally, the everted intestinal segment technique has the potential to be used in other species and with different contaminants. [source] Effects of aromatic amino acids, phenylacetate and phenylpropionate on fermentation of xylan by the rumen anaerobic fungi, Neocallimastix frontalis and Piromyces communisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2007A.Y. Guliye Abstract Aims:, Anaerobic fungi are important members of the fibrolytic community of the rumen. The aim of this study was to study their requirement for aromatic amino acids (AA) and related phenyl acids (phenylpropionic and phenylacetic acids) for optimal xylan fermentation. Methods and Results:,Neocallimastix frontalis RE1 and Piromyces communis P were grown in a defined medium containing oat spelts xylan as the sole energy source, plus one of the following N sources: ammonia; ammonia plus a complete mixture of 20 AA commonly found in protein; ammonia plus complete AA mixture minus aromatic AA; ammonia plus phenyl acids; ammonia plus complete AA mixture without aromatic AA plus phenyl acids. Both species grew in all the media, indicating no absolute requirement for AA. The complete AA mixture increased (P < 0·05) acetate concentration by 18% and 15%, sugar utilization by 33% and 22% and microbial yield by about 22% and 15% in N. frontalis and P. communis, respectively, in comparison with the treatments that had ammonia as the only N source. Neither the supply of aromatic AA or phenol acids, nor their deletion from the complete AA mixture, affected the fermentation rate, products or yield of either species. Conclusions:, AA were not essential for N. frontalis and P. communis, but their growth on xylan was stimulated. The effects could not be explained in terms of aromatic AA alone. Significance and Impact of the Study:, Ruminant diets should contain sufficient protein to sustain optimal fibre digestion by ruminal fungi. Aromatic AA or phenyl acids alone cannot replace the complete AA mixture. [source] | ||||||||||||||||