Therapeutic potential of amniotic fluid stem cells to treat bilateral ovarian dystrophy in dairy cows in a subtropical region.

Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti-inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein-Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein-Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast-like morphology. They were positive for ß-integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10-15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility.

Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance.

AIMS/HYPOTHESIS: We examined in skeletal muscle (1) whether fatty acid transport protein (FATP) 1 channels long-chain fatty acid (LCFA) to specific metabolic fates in rats; and (2) whether FATP1-mediated increases in LCFA uptake exacerbate the development of diet-induced insulin resistance in mice. We also examined whether FATP1 is altered in insulin-resistant obese Zucker rats. METHODS: LCFA uptake, oxidation and triacylglycerol esterification rates were measured in control and Fatp1-transfected soleus muscles to determine FATP1-mediated lipid handling. The effects of FATP1 on insulin sensitivity and triacylglycerol accumulation were determined in high-fat diet-fed wild-type mice and in muscle-specific Fatp1 (also known as Slc27a1) overexpressing transgenic mice driven by the muscle creatine kinase (Mck [also known as Ckm]) promoter. We also examined the relationship between FATP1 and both fatty acid transport and metabolism in insulin-resistant obese Zucker rats. RESULTS: Transient Fatp1 overexpression in soleus muscle increased (p < 0.05) palmitate transport (24%) and oxidation (35%), without altering triacylglycerol esterification or the intrinsic rate of palmitate oxidation in isolated mitochondria. In Mck/Fatp1 animals, Fatp1 mRNA and 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid uptake in skeletal muscle were upregulated (75%). However, insulin sensitivity and intramuscular triacylglycerol content did not differ between wild-type and Mck/Fatp1 mice following a 16 week high-fat diet. In insulin-resistant obese Zucker rats, LCFA transport and triacylglycerol accumulation were increased (85% and 24%, respectively), but this was not attributable to Fatp1 expression, as neither total cellular nor sarcolemmal FATP1 content were altered. CONCLUSIONS/INTERPRETATION: Overexpression of Fatp1 in skeletal muscle increased the rate of LCFA transport and channelled these lipids to oxidation, not to intramuscular lipid accumulation. Therefore, skeletal muscle FATP1 overabundance does not predispose animals to diet-induced insulin resistance.

Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.

AIM: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D). METHODS: Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA(1.5%) and SA(15%) , respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA(15%) groups. RESULTS: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA(15%) group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA(15%) compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA(15%) compared with Ctrl suggesting a reduced hepatic glucose output induced by SA. CONCLUSION: Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output.

C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment.

We have identified and characterized a novel C. elegans gene, ced-12, that functions in the conserved GTPase signaling pathway mediated by CED-2/Crkll, CED-5/DOCK180, and CED-10/Rac to control cell migration and phagocytosis of apoptotic cells. We provide evidence that ced-12 likely acts upstream of ced-10 during cell migration and phagocytosis and that CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro. We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. We suggest that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as CED-12 does in C. elegans.

Tunable PEGylation of branch-type PEI/DNA polyplexes with a compromise of low cytotoxicity and high transgene expression: in vitro and in vivo gene delivery.

Although PEGylated polyplexes for gene delivery are widespread, there is a need for an in-depth investigation of the role of the PEGylation degree on the delivery efficiency of the systems. For this, a low-toxicity series of polymers for gene delivery were designed via Michael addition of poly(ethylene glycol)methyl ether methacrylate (PEGMA) onto branched polyethylenimine PEI. The goal was to finely tune the PEGylation degree in order to determine the system offering the best compromise between low cytotoxicity and high transfection efficiency under both in vitro and in vivo conditions. From dynamic light scattering tests, zeta potential measurements and gel retardation assay, it was found that nanoparticle assembly of PEI-g-PEGMA and DNA exhibited stable complex formation when the PEGylation degree was below 2.9%. In addition, complexes formed from polymers with a PEGylation degree of at least 1.67% (from PEI-g-PEGMA-6 to PEI-g-PEGMA-18) all showed very low hemolysis activity. Transfection efficiencies of the prepared complexes were determined using the pEGFP-C3 vector and ß-galactosidase. Complexes made of PEI-g-PEGMA-6 and PEI-g-PEGMA-10 at a polymer nitrogen/DNA phosphorus weight ratio (Wn/Wp) of 5 led to the best transfection efficiencies. Moreover, PEGylation ensured low cytotoxicity of the complexes in particular at high Wn/Wp ratios. In vivo tests in a mouse model confirmed the in vitro results obtained for PEI-g-PEGMA-6-based complexes, at all Wn/Wp ratios tested, but also showed that a high PEGylation degree (5.2% for PEI-g-PEGMA-18), though inefficient in vitro could still lead to successful delivery in vivo, due to a prolonged contact time between the complex and the cells, and to the change in the biological environment. Overall, provided a fine tuning of the grafting density of PEGMA onto PEI and the polymer nitrogen/DNA phosphorus weight ratio, our results prove that PEI-g-PEGMA polymers constitute an efficient platform for successful in vitro and in vivo gene delivery, and ensure low cytotoxicity and prolonged cell viability.

Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in males and females in the world. It is of immediate importance to develop novel therapeutics. Human ribonucleotide reductase (RRM1/RRM2) has an essential role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools. RRM2 is a prognostic biomarker and predicts poor survival of CRC. In addition, increased RRM2 activity is associated with malignant transformation and tumor cell growth. Bioinformatics analyses show that RRM2 was overexpressed in CRC and might be an attractive target for treating CRC. Therefore, we attempted to search novel RRM2 inhibitors by using a gene expression signature-based approach, connectivity MAP (CMAP). The result predicted GW8510, a cyclin-dependent kinase inhibitor, as a potential RRM2 inhibitor. Western blot analysis indicated that GW8510 inhibited RRM2 expression through promoting its proteasomal degradation. In addition, GW8510 induced autophagic cell death. In addition, the sensitivities of CRC cells to GW8510 were associated with the levels of RRM2 and endogenous autophagic flux. Taken together, our study indicates that GW8510 could be a potential anti-CRC agent through targeting RRM2.

Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae.

Effects of ergosterol peroxide (C28H44O3; Cpd 6A) from Cordyceps cicadae on phytohemagglutinin (PHA)-stimulated cell proliferation were studied in primary human T cells. The results showed that Cpd 6A suppressed T-cell proliferation for about 24 h after stimulation with PHA. Cell cycle analysis indicated that Cpd 6A arrested the cell cycle progression of activated T cells from the G1 transition to the S phase. To localize the point in the cell cycle where arrest occurred, a set of key regulatory events leading to the G1/S boundary, including the expression of cyclins D2, E, A1, and B1, interleukin (IL)-2, IL-4, interferon-gamma (IFN-gamma), and activating protein-1 (AP-1), was examined. Cpd 6A suppressed, in activated T lymphocytes, the production and mRNA expression of cyclin E, IL-2, IL-4, IL-10, and IFN-gamma in a dose-dependent manner. Expression of AP-1 proteins, consisting of c-Fos and c-Jun, in activated T lymphocytes was decreased by Cpd 6A. The kinetic study indicated that the inhibitory effects of Cpd 6A on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. T-cell proliferation after Cpd 6A treatment was partially restored by addition of IL-2, IL-4, and IFN-gamma. These suppressant effects of Cpd 6A on T-cell proliferation, activated by PHA, appeared to be mediated, at least in part, through the inhibition of early gene transcripts, especially those of cyclin E, IFN-gamma, IL-2, and IL-4, and by arresting cell cycle progression in the cells.

High-fat diet feeding reduces the diurnal variation of plasma leptin concentration in rats.

To investigate the response of plasma leptin and its diurnal variation to graded levels of dietary fat intake, adult (486.8+/-10.8 g), male rats (N = 52) were fed diets containing 12%, 28%, 44%, and 60% fat for 4 weeks. The body weight gain and abdominal fat pad weight were higher (P < .05) in groups fed diets containing 44% and 60% fat compared with the two diets containing less fat. There were no significant differences in terms of body weight or fat pad weight between animals fed the two diets with higher fat content or between animals fed the two lower-fat diets. Twenty-four-hour energy expenditure was not different among the dietary fat groups. After 3 days on the experimental diets, plasma leptin increased (P < .03) in all dietary groups. The increases in leptin in animals fed 12% and 28% fat diets occurred primarily in the morning. In contrast, in groups fed the two diets containing higher fat content, leptin levels increased mainly in the afternoon. As a result, the daily variation in leptin increased (P < .05) in the two groups fed lower-fat diets, but decreased (P < .04) in animals fed the two higher-fat diets. These data demonstrate that short-term high-fat diet feeding abolished the diurnal fluctuation of plasma leptin levels, which may prevent proper leptin function and eventually contribute to the development of obesity.

Effects of methanol extract of Chansu on hypothalamic-pituitary-testis function in rats.

Chansu, a galenical preparation of the dried white venom of Chinese Bufo bufo gargarizans, is one of the major components of Kyushin, a traditional Chinese medicine. Kyushin is reported to have a cardiotonic effect that has been suggested to be due to the action of bufadienolides such as bufalin and cinobufagin. Recently, we found that administration of bufalin in male rats diminished the luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) and the secretion of testosterone both in vivo and in vitro. These observations suggest that Chansu may possess hypogonadal effects in male rats. In the present study, the effects of the methanol extract of Chansu on hypothalamic-pituitary-testicular function in male rats were examined. Crude Chansu was extracted by methanol and purified by a Sep-Pak C18 column. No activity of bufalin, cinobufagin, estradiol, or digoxin in purified methanol extract was detected; all Chansu used in this study was the purified methanol extract. A single intravenous injection of Chansu resulted in a decrease of the basal (20% to 55%) and human chorionic gonadotropin (hCG)-induced (35% to 40%) levels of plasma testosterone and the GnRH-induced level of plasma LH (25% to 30%). Administration of Chansu in vitro decreased basal and hCG-stimulated testosterone production by 60% to 70% and 40% to 60%, respectively, as well as spontaneous and forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) by 30% to 45% in rat testicular interstitial cells. Although LH release by rat anterior pituitary glands was diminished, GnRH release by the rat mediobasal hypothalamus was enhanced by administration of Chansu in vitro. These results suggest that the bufalin-free extracts of Chansu inhibit testosterone secretion in rats, in part, due to (1) a decreased production of testicular cAMP, (2) a decreased response of testosterone to gonadotropin, and (3) a reduction of the LH response to GnRH.

The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action.

The roles of the endothelium, Ca2+ and K+ fluxes in the evodiamine-induced attenuation of vascular contractile responses to vasoactive agents were examined. The results showed that: (1) in rat mesenteric artery rings, evodiamine elicited a concentration-dependent attenuation in the contractile response generated by phenylephrine. The inhibitory potency was greater for intact than for endothelium-denuded preparations. Thus, the vasodilator action of evodiamine appeared to be partially endothelium-interactive (dependent). (2) Evodiamine pretreatment had a greater inhibitory effect on the phenylephrine-induced tonic contraction (via Ca2+ influx) than on the phasic contraction (via Ca2+ release). In addition, evodiamine was more potent to inhibit the restoration by CaCl2 of contractile responses to phenylephrine than a potassium depolarizing solution in media that had been kept calcium-free. These results suggest that block of the Ca2+ influx through receptor-mediated Ca2+ channels may be the major mechanism underlying the vasodilator effect of evodiamine. (3) A K+ channel blocker, tetraethylammonium, almost completely abolished the vasodilatation induced by minoxidil (a known K+ channel opener) but not evodiamine. The possible involvement of K+ channel activation of the vasodilator effect produced by evodiamine was therefore excluded.

The mechanism of the vasodilator effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa.

The mechanisms underlying the rutaecarpine-induced vasodilatation were studied using isolated rat mesenteric arterial ring segments. The results showed that rutaecarpine (0.1 microM to 0.1 mM) produced a dose-dependent vasorelaxing response in our preparations, which were precontracted with phenylephrine. This vasodilator effect was significantly attenuated by removal of the endothelium, treatment with L-NG-nitro-arginine, a nitric oxide synthase inhibitor, and methylene blue, a guanylyl cyclase inhibitor, but not by treatment with atropine, triprolidine and yohimbine. Rutaecarpine pretreatment (1 microM to 0.1 mM) reduced both the phasic (fast) and tonic (slow) phases of phenylephrine-induced contractions, suggesting that a reduction in intracellular calcium might be involved. It is thus concluded that while the vasorelaxing effect of rutaecarpine appeared to be endothelium-dependent and to involve nitric oxide and guanylyl cyclase, neither muscarinic receptors, histamine H1 receptors nor alpha 2-adrenoceptors are involved. Moreover, a direct effect on the vascular smooth muscle cell, possibly through a reduction in intracellular Ca2+, can not be excluded.

Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice.

Dehydroevodiamine has been reported to have anticholinesterase activity and an anti-amnesic effect. This study examined the effects of dehydroevodiamine on scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia in mice, using a step-through passive avoidance test. Similarly to the cholinesterase inhibitor, physostigmine (0.03--0.3 mg/kg, i.p.), dehydroevodiamine (0.75--12.0 mg/kg, i.p.) administered 30 min before the training trial, immediately after the training trial, and 30 min before the retention test significantly improved scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia. In beta-amyloid peptide-(25--35)-induced amnesia, the rank order of anti-amnesic potency in these three administration schedules for dehydroevodiamine was different from that for physostigmine. Furthermore, dehydroevodiamine was more potent to improve beta-amyloid peptide-(25--35)-induced amnesia than scopolamine-induced amnesia when administered before the training trial. These results suggested that dehydroevodiamine may have an action other than that of an anticholinesterase and may be a novel and effective ligand for improvement of beta-amyloid type amnesia.

Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules.

Baicalein, a flavonoid present in the root of Scutellaria baicalensis Georgi, has been reported to inhibit cell proliferation in several types of cells. In this study, the effect of baicalein on cell growth and the mechanism of growth modulation were examined in primary cultured rat heart endothelial cells. Here, we report that treatment with 100-microM baicalein caused an almost complete inhibition of cell proliferation after 5 days of incubation. Baicalein mediated G1 and G2 growth arrest accompanied by the down-regulation of cyclin D2, cyclin A, cyclin-dependent kinase 1 (Cdk1) and cyclin-dependent kinase 2 (Cdk2), and up-regulation of p15(Ink4B), p21(CIP1/Waf1), p53 and cyclin E. Evaluation of the kinase activity of cyclin-Cdk complexes showed that baicalein decreased Cdk1, Cdk2, cyclin D2 and cyclin A expression in endothelial cells, leading to markedly reduced Cdk/cyclin-associated kinase activities. These results suggest that baicalein inhibits the proliferation of rat heart endothelial cells via G1 and G2 arrest in association with the down-regulation of the expression and function of Cdk1, Cdk2, cyclin D2 and cyclin A proteins, and up-regulation of cyclin E, p15(Ink4B), p53 and p21(CIP1/Waf1).

Camptothecin suppresses nitric oxide biosynthesis in RAW 264.7 macrophages.

Nitric oxide is an important cellular mediator that plays a role in tumor growth and angiogenesis. The present study was conducted to evaluate whether camptothecin (CPT), a topoisomerase I inhibitor, exhibits antitumor activity through regulation the inducible nitric oxide synthase (iNOS) biosynthesis pathway. Experiment was performed on RAW 264.7 cells, a transformed macrophage-like cell line, stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Incubation of RAW264.7 cells with CPT (0.1 to 10 microM) inhibited the LPS/IFN-gamma-induced nitrite accumulation in a concentration-dependent manner with an IC50 value of 0.59+/-0.07 microM. Treatment of cells with concentrations of CPT (< or =3 microM) that are not growth inhibitory or cytotoxic strongly inhibited their ability to express iNOS mRNA and iNOS protein, however, without a direct regulatory effect on iNOS activity. Time course analysis also revealed that CPT acted in a fashion similar to the transcription inhibitor actinomycin-D. Thus, the suppressant effects of CPT on LPS/IFN-gamma-stimulated NO production seemed to be mediated probably through inhibition of iNOS gene transcription. From this observation we propose that inhibition of NO biosynthesis by CPT may underlie, at least in part, the efficacy of this antitumor agent.

Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis.

Cordyceps sinensis is a herb medicine in China for the treatment of general debility after sickness and for persons of advanced age. In the present study, cordyceps sinensis was extract by phosphate buffer saline (PBS) and dialyzed overnight against PBS using a membrane cut off at 3,500 dalton molecular weight. The resulting macromolecule fraction (defined as CS) was assayed in anesthetized rats for hypotensive effects and in isolated aorta for vasorelaxant effects. Intravenous injection of CS (8,16, 24 and 32 mg/kg, respectively) suppressed significantly the mean arterial pressure (MAP) in a dose-dependent manner. 32 mg/kg of CS induces the maximal hypotensive response with a 58 +/- 4 mm Hg (from 107 +/- 6 to 49 +/- 3 mm Hg) change in MAP and a over 45 min action duration. In aortic rings precontracted with phenylephrine treatment with CS between 0.5 and 500 microg/ml induced dose dependent relaxation. Maximal vasorelaxant response evoked by 150 microg/ml CS was 68.9 +/- 7.3%. Furthermore, CS-induced vasorelaxation is mediated by the endothelium possibly by stimulating the release of the nitric oxide and endothelium-derived hyperpolarizing factor. In conclusion, the present study revealed that presence of a constituent in CS which reduces MAP by relaxing the vascular beds directly. However, the effect may be caused by a single active ingredient or by the combined action of many active agents found in the extract.

Measurement and pharmacokinetics of unbound 20(S)-camptothecin in rat blood and brain by microdialysis coupled to microbore liquid chromatography with fluorescence detection.

To characterize the pharmacokinetics of protein-free camptothecin in blood and brain we implanted microdialysis probes into the jugular vein and striatum of rats for unbound drug sampling and determination. Camptothecin (2 or 5 mg/kg, i.v., n=6) was then administered from the femoral vein, and microdialysates were collected from blood and brain of both sites and assayed by a validated microbore scale high-performance liquid chromatographic method. The mobile phase consisted of methanol-100 mM monosodium phosphoric acid (35:65, v/v, pH 2.5) with a flow-rate 0.05 ml/min. The fluorescence response for camptothecin was observed at excitation and emission wavelengths of 360 and 440 nm, respectively. Pharmacokinetic parameters were calculated from the corrected data for dialysate concentrations of camptothecin versus time. The results suggest that the pharmacokinetics of unbound camptothecin in blood and brain can be fitted best to a two- and one-compartment model, respectively. Camptothecin rapidly entered the extracellular fluid of brain striatum at 10 min following camptothecin administration.

Pharmacokinetics of paeonol after intravenous administration in rats.

A simple high-performance liquid chromatography methodology was developed to study the pharmacokinetics of paeonol in the rat after intravenous (iv) bolus administration of various doses (2.5, 5, or 10 mg/kg). The pharmacokinetics of paeonol in rat plasma at each dose were well described by a two-compartment model. The area under the curve increased proportionally with dose and consequently total body clearance was independent of dose. There was no dose-related difference in the elimination half-life or volume of distribution. These results indicate that the pharmacokinetics of paeonol after iv administration are linear over the 2.5-10 mg/kg dose range.

Pharmacokinetics and brain distribution of magnolol in the rat after intravenous bolus injection.

The pharmacokinetics of magnolol in rats was studied after 2, 5, or 10 mg/kg-1 intravenous bolus injection. Plasma concentration-time profiles of magnolol were fitted by a two-compartment open model. There were no significant differences in the elimination half-life, the total body clearance, steady-state volume of distribution, or mean residence time. The area under the plasma-time curve and area under the moment-time curve of magnolol appears to increase proportionally from a dose of 2 to 10 mg/kg-1. These results suggest that magnolol possess linear pharmacokinetics. Notwithstanding, brain concentration of magnolol showed no significant difference among various regions (cerebral cortex, olfactory bulb, hippocampus, striatum, cerebellum, brain stem and rest of brain) after 10 min of magnolol (5 mg/kg-1, i.v.) administration, the mean brain drug concentration was approximately fourfold that of magnolol in plasma.

The chelating treatment is not useful in human's intoxication with acute herbicidal organic arsenic.

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.

PROP taster status and oral fatty acid perception.

Recent studies with rat taste cells treated with polyunsaturated fatty acids suggest that fatty acids may play a role in dietary fat perception. In humans, sensitivity to the textural properties of fat is associated with the genetic ability to taste the bitter compound 6-N-2-propylthiouracil (PROP). However, it has not been shown that PROP tasters are more sensitive in discriminating fatty acids in a high-fat food. Our study with human subjects was designed to test the hypothesis that the ability to orally detect food-grade conjugated linoleic acid added to high-fat vanilla ice cream is associated with the ability to taste PROP. Eighty percent of the PROP tasters in this study, but only 17% of the PROP nontasters correctly discriminated the sample containing the added free fatty acid in a difference test versus unadulterated high-fat vanilla ice cream (Fisher's Exact Test, P=.05). Because most fatty foods contain minute amounts of free fatty acids, further studies with humans examining the contribution of fatty acids to fat perception seem warranted.