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PubMed1998

An in vitro method, based on chewing, to predict resistant starch content in foods allows parallel determination of potentially available starch and dietary fiber.

The purpose of this work was to develop a method for measurement of the major forms of resistant starch (RS) in foods. The analytical procedure was chosen to mimic physiologic conditions, and included chewing as a prestep before incubation with pepsin, pancreatin and amyloglucosidase. The undigestible polysaccharides, including RS, were recovered by ethanol precipitation and subsequent filtration. RS was analyzed as total starch in the filter residue. The residues were also used for gravimetric determination of dietary fiber after correcting for remaining protein, ash and RS. The potentially available starch fraction was determined from analysis of glucose in the filtrate. The foods included were prepared to resemble products for which RS figures were available from in vivo measurements, and/or from analysis with other current in vitro methods. For six of these foods, and for three additional starchy materials, RS figures were compared with in vivo and/or in vitro data for identical products. The pooled standard deviation for the suggested RS method was 2.9%. A high correlation was obtained with in vivo figures from the literature for 19 realistic foods (r = 0.97; y = 0.77x + 0.45). After correction for RS, dietary fiber figures corresponded well with conventional gravimetric dietary fiber analysis for 14 starchy foods (r = 0.97). It is concluded that the procedure described here provides a convenient way to estimate RS content of realistic foods, allowing parallel determination of the potentially available starch fraction and dietary fiber.

Biological Availability↗

PubMed2003

Arginine availability, arginase, and the immune response.

PURPOSE OF REVIEW: Arginine, often found in immunonutrition regimens, is an important modulator of immune system activation. However, the mechanism of how arginine may be beneficial in immunonutrition is poorly understood. This review details the importance of arginine, its metabolism, and ultimately, its physiologic role in critically ill and immunocompromised patients. RECENT FINDINGS: The metabolism of arginine is determined by the expression of the arginine metabolizing enzymes inducible nitric oxide synthase and two arginase isoforms (arginase I and II). Inducible nitric oxide synthase is induced by T helper I cytokines (interleukin-1, tumor necrosis factor and gamma-interferon), while arginases are induced by T helper II cytokines and other immune regulators such as interleukins 4, 10, and 13, transforming growth factor-beta and prostaglandin E2. Endotoxin induces inducible nitric oxide synthase and arginases I and II. Arginase plays an important role in the production of ornithine, a precursor of proline and polyamines, both of which are necessary for cellular proliferation and wound healing. Arginase also induces nitric oxide synthase activity by competing for arginine availability in the extracellular environment, and producing polyamines, which may modulate macrophage activation. Through limitation of arginine availability in the extracellular environment, arginases also potentially regulate other 'arginine-dependent' immune functions such as T-lymphocyte activation, although this hypothesis remains to be proven. SUMMARY: The availability of arginine during critical illness may be regulated by arginase activity. Thus, arginase expression appears to be essential in the regulation of the cellular immune response and the inflammatory process during critical illness.

Arginase↗

PubMed1991

Assessment of iron availability using stable 54Fe.

This paper describes a method of quantitatively assaying the bioavailability of orally administered iron in order to promote haemoglobin synthesis in iron deficiency anaemia. The non-radioactive tracer substance 54Fe was employed. An experimental iron deficiency model was tested in 18 healthy male volunteers. The trial design made it possible to assess intestinal absorption and efficacy of iron substitution. The iron deficiency was experimentally induced by weekly phlebotomy. Two commercially available iron preparations with different rates of iron release were investigated at a dosage of 150 and 160 mg Fe2+ daily, respectively. In the first seven days of treatment, both preparations were administered in 54Fe-labelled form. Afterwards, iron substitution was given with the commercially available preparations. Measurements were made of erythrocyte utilization of 54Fe and plasma iron tolerance curves at the beginning of the periods in which the 54Fe-labelled product and the commercially available preparation were administered, and of haemoglobin and serum ferritin concentration curves over three months. The mean utilization of the iron administered was virtually identical for the two preparations (23 and 22%, respectively). Likewise, there was no difference with respect to the average daily increase in haemoglobin concentration in the blood (1.5 g 1-1). There was also no significant difference with respect to serum ferritin concentration curves. In contrast, the two preparations differed markedly with respect to the plasma iron tolerance curves. This suggests that evaluation of plasma iron tolerance curves alone is not suitable for comparative assessment of the therapeutic value of orally administered iron preparations.

Administration, Oral↗

PubMed1992

Formulation and (bio)availability problems of drug formulations in birds.

Most drugs used for the treatment of birds are not formulated for birds. Therefore the availability of drugs for birds and their administration routes largely depend on formulations available for man, mammals and to some extent poultry. The problems with the application of existing formulations, the drug concentrations and the many different avian species are discussed. The desire of the avian veterinarian for the combination of several active compounds presents special problems. This again requires extra data on the interactions in galenic, pharmaceutic, pharmacokinetic and dynamic phases, which are generally not readily available.

Animal Feed↗

PubMed1999

Systemic availability and pharmacokinetics of nebulised budesonide in preschool children.

AIM: To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma. METHODS: Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 micrograms budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amount remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water. RESULTS: Ten patients aged 3 to 6 years completed both the intravenous and the inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0 to 2.6). CONCLUSIONS: Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser.

Anti-Inflammatory Agents↗

PubMed2004

Effects of reduced free fatty acid availability on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise.

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerol (IMTG); however, its regulation in skeletal muscle is poorly understood. To examine the effects of reduced free fatty acid (FFA) availability on HSL activity in skeletal muscle during aerobic exercise, 11 trained men exercised at 55% maximal O2 uptake for 40 min after the ingestion of nicotinic acid (NA) or nothing (control). Muscle biopsies were taken at rest and 5, 20, and 40 min of exercise. Plasma FFA were suppressed (P < 0.05) in NA during exercise ( approximately 0.40 +/- 0.04 vs. approximately 0.07 +/- 0.01 mM). The respiratory exchange ratio (RER) was increased throughout exercise (0.020 + 0.008) after NA ingestion. However, the provision of energy from fat oxidation only decreased from 33% of the total in the control trial to 26% in the NA trial, suggesting increased IMTG oxidation in the NA trial. Mean HSL activity was 2.25 + 0.15 mmol x kg dry mass(-1) x min(-1) at rest and increased (P < 0.05) to 2.94 +/- 0.20 mmol x kg dry mass(-1) x min(-1) at 5 min in control. Contrary to the hypothesis, mean HSL was not activated to a greater extent in the NA trial during exercise (2.20 + 0.28 at rest to 2.88 + 0.21 mmol x kg dry mass(-1) x min(-1) at 5 min). No further HSL increases were observed at 20 or 40 min in both trials. There was variability in the response to NA ingestion, as some subjects experienced a large increase in RER and decrease in fat oxidation, whereas other subjects experienced no shift in RER and maintained fat oxidation despite the reduced FFA availability in the NA trial. However, even in these subjects, HSL activity was not further increased during the NA trial. In conclusion, reduced plasma FFA availability accompanied by increased epinephrine concentration did not further activate HSL beyond exercise alone.

Adult↗

PubMedDate not supplied

Determinants of insulin availability in parenteral nutrition solutions.

BACKGROUND: Management of hyperglycemia in patients receiving parenteral nutrition (PN) often includes the addition of regular insulin to the PN solution. A literature review has shown insulin availability in such solutions to range from 10% to 95%. This discrepancy in availability may be due to differences in the composition of the PN solution, the final concentration of insulin, or the assay method used to determine insulin concentrations. The purpose of this study was to evaluate insulin recovery from a standard PN solution used at our medical center. METHODS: Solutions were manually prepared in our pharmacy according to standard practice. Multivitamins and trace elements were added to 1 of 2 L of solution each day. Each of 3 simulated patients received 2 L of solution per day for 3 consecutive days. Samples from each bottle were drawn at baseline, 1 hour after the start of infusion, and 1 hour before the end of infusion and were subsequently analyzed for immunoreactive insulin levels by radioimmunoassay. RESULTS: Recovery of insulin from solutions containing multivitamins and trace elements was much greater (95%) than from those without (5%). CONCLUSIONS: The presence of multivitamins and trace elements is a major determinant of insulin availability in PN solutions. Additional research is necessary to determine the mechanism mediating this effect and to assess its clinical significance.

Biological Availability↗

PubMedDate not supplied

Availability of cysteine and of L-2-oxo-thiazolidine-4-carboxylic acid as a source of cysteine in intravenous nutrition.

Cysteine is usually not included in amino acid solutions for intravenous nutrition for two reasons: it is not considered to be an essential amino acid, and it causes stability problems in solutions. The cysteine content of a solution decreases markedly in the presence of oxygen and/or glucose due to formation of various derivatives, such as cystine and D-glucocysteine. It is not clear if the formed derivatives are available for metabolic processes. A cysteine analogue, L-2-oxothiazolidine-4-carboxylic acid (OTCA), is stable in solutions and can be metabolized in the body-yielding cysteine. The metabolic availability of cysteine and OTCA from an all-in-one total parenteral nutrition (TPN) mixture was evaluated in the rat and compared to a regimen with cysteine infused from a separate container. A cysteine-free TPN mixture served as a control. All mixtures contained a suboptimal amount of methionine, which can normally be metabolized to cysteine, to enhance the nutritional effect of cysteine or OTCA supplement. The cysteine content in the admixture decreased approximately 40% during 30 hr after mixing. Nevertheless the utilization of this admixture was identical to the regimen supplying cysteine separately. The admixture containing OTCA showed similar results as the two cysteine regimens. All three regimens promoted growth significantly better than the cysteine-free-mixture. The results suggest that 1) cysteine is available for metabolic processes from its derivatives formed in an all-in-one TPN mixture, and 2) OTCA acts as a precursor of cysteine to the rat when supplied as a part of TPN.

Animals↗

PubMed1988

Comparative dissolution performance of internationally available piroxicam products.

Piroxicam is a widely used nonsteroidal antiinflammatory drug available worldwide under various trade names by several manufacturers. Only one brand of piroxicam (Feldene) is currently marketed in the U.S., and the United States Pharmacopeial Convention established an official dissolution requirement for piroxicam in 1985. The purpose of this study was to evaluate and compare the dissolution performance of several internationally available piroxicam products using the United States Pharmacopeia (USP) dissolution test for piroxicam capsules. Of 25 brands of piroxicam capsules evaluated, 72 percent of the brands failed to meet the USP requirement, several by a wide margin. Although there is no specific USP dissolution test for tablets, the test for capsules was applied to five different brands of piroxicam tablets, and 80 percent of the tablet brands tested failed to meet the USP requirement. Although comparative bioavailability studies would be required to establish any definitive relationship between dissolution test performance and bioavailability, the failure of most of these products to meet the USP requirement for dissolution indicates formulation differences that could result in altered bioavailability. The substantial differences in dissolution performance observed among the piroxicam oral dosage forms tested have implications concerning the equivalency and standards of multisource products available on the international market, and should be taken into account by health care providers worldwide.

Biological Availability↗

PubMed1996

Suppression of luteinizing hormone pulses by restriction of glucose availability is mediated by sensors in the brain stem.

The availability of metabolic fuels such as glucose is known to influence reproductive function. Peripheral administration of 2-deoxyglucose (2DG), a competitive inhibitor of glycolysis, inhibits pulsatile LH secretion in the rat and growth-retarded lamb. We hypothesized that such glucoprivic suppression of LH secretion is mediated by the lower brain stem, because studies of both ingestive and reproductive behavior implicate lower brain stem structures, such as the area postrema, as a site that is sensitive to glucose availability. In the present study, the effect of a 2DG infusion, targeted to the fourth ventricle, on pulsatile LH secretion was examined in male rats. The males were castrated or castrated and immediately implanted with testosterone. Blood samples were collected through an indwelling atrial cannula every 6 min for 4 h for LH determination. After the first hour of blood sampling, 2DG (4 or 40 mg/kg) was infused into the fourth ventricle at a flow rate of 0.2 microliter/min through a cannula that had been stereotaxically implanted 1 week before sampling. The high dose of 2DG (40 mg/kg), but not the low dose (4 mg/kg), suppressed pulsatile LH secretion and increased food intake in both castrated and testosterone-treated castrated rats. LH secretion and food intake were not affected by the infusion of xylose (40 mg/kg) as an isoosmotic control. The site specificity of the 2DG treatment was confirmed by histological examination after an isovolumetric infusion of dye (0.2 microliter/min). These results suggest that glucose availability could influence LH secretion as well as feeding through a central sensor in the lower brain stem and are consistent with the idea that the area postrema might be an important glucosensor involved in the modulation of LH secretion.

Animals↗

PubMed1989

Enteric solid dispersion of cyclosporin A (CyA) having potential to improve availability of CyA in rabbit.

The availability of cyclosporin A (CyA) administered as an enteric solid dispersion preparation of which the composition is CyA:HCO-60:HP-55 = 1:2:8 was evaluated in rabbits. The additives are surfactant (polyoxyethylated, 60 mumol, castor oil derivative, HCO-60) and enteric coating material (hydroxypropylmethyl cellulose phthalate, HP-55), which are generally used as pharmaceutical additives. Both the systemic and lymphatic availabilities of CyA from this solid preparation were measured in rabbits after intrastomach administration, 7 mg CyA/kg, and were compared with those from conventional oily solution, Sandimmun. The mean systemic availability of CyA from the solid preparation was 57% which is about 1.5 times greater than that obtained from Sandimmun. The amounts of CyA transferred into the thoracic lymphatics within 12 h from solid dosage form and Sandimmun are 0.62 +/- 0.16(S.D.)% and 0.13 +/- 0.05% of the administered CyA dose. These results support the usefulness of the new solid dosage form of CyA.

Animals↗

PubMed2005

Eberconazole cream: topical and general tolerability, sensitisation potential, and systemic availability.

Eberconazole is a topical imidazole derivative, which has shown high potency against dermatophytes and yeasts (several species of Candida, Malassezia) in vitro and in experimental models. Clinical trials have found that the compound has a high degree of efficacy against dermatophytes and good tolerability. Evaluation of its a) topical and general tolerability, b) eventual development of sensitisation, c) local availability, and d) degree of systemic absorption. Two clinical trials with 28 healthy young volunteers of both sexes were performed. In Study I, placebo or eberconazole cream (2%) were applied at increasing doses: day 1 (0.5 g), days 2-3 (1 g), days 4-5 (2 g), days 6-7 (4 g), days 8-9 (8 g), and days 10-11 (12 g). On day 1, each application area was washed with ethanol-soaked gauzes at different times to assess availability of the active compound. In Study II, eberconazole cream (1%) was applied on day 1 and again at least one week later. After the first application, blood and urine samples were obtained at different times to assess systemic absorption. The only change observed was slight redness in a few volunteers after both active and placebo applications. This remitted spontaneously without intervention and we were able to continue with the administration of repeated increasing-doses. A few participants described side effects; these were all of mild intensity, and occurred in areas where placebo or eberconazole were applied, mainly within the first hour postapplication. The most frequent effect after the first application was coldness, and after repeated increasing-doses there was itching. No signs or symptoms of skin reactivity were observed following reexposure to the product. No clinically relevant changes were observed in vital signs (systolic and diastolic blood pressure, heart rate, body temperature), ECG, or analytical parameters (clinical haematology and biochemistry). The quantity of compound collected through washing gauzes decreased progressively over time. Plasma and urine concentrations of eberconazole were below the quantification limit of the analytical method (5 ng/ml) at all times. Eberconazole cream is a topical antimycotic drug that has good local and general tolerability. It has acceptable topical availability, no detectable systemic drug levels, and does not appear to cause skin sensitivity.

Administration, Topical↗

PubMed2001

Evaluation of fluoride release from commercially available fluoride varnishes.

BACKGROUND: The authors conducted a study to evaluate the fluoride released from two fluoride varnishes: Duraphat (Colgate-Palmolive Co., New York) and Duraflor (Pharmascience Inc., Montreal). Fluoride-release information for these commercially available dental products has not been available to clinicians treating children at risk of developing dental caries. METHODS: The authors painted enamel slabs from primary molar teeth with 30 milligrams of two varnishes: nine samples received Duraphat, nine received Duraflor and five samples served as controls. The samples were immersed in buffered calcium phosphate solution (pH, 6.0) to simulate the oral environment, and the amount of fluoride released was measured weekly for six months. RESULTS: From week 4 to the end of the study, Duraphat released significantly more fluoride than Duraflor. Duraflor continued releasing fluoride until week 19, while Duraphat released fluoride until week 28. The authors found greater variability in the release of fluoride from the Duraflor samples than from the Duraphat samples. Two-thirds of the fluoride was released from both products by the end of the study. CONCLUSIONS: Both varnishes released fluoride for five to six months. However, the two products exhibited differences in their release kinetics. CLINICAL IMPLICATIONS: These findings show that either of the fluoride varnishes may maintain a high level of fluoride in plaque fluid around primary teeth over a long period, but that the availability of fluoride may vary among tubes of the same product and between the two products themselves.

Biological Availability↗

PubMedDate not supplied

Phytase, high-available-phosphorus corn, and storage effects on phosphorus levels in pig excreta.

Phosphorus-based land application limits for manure have increased the importance of optimizing diet P management and accurately characterizing the bioavailability of manure P. We examined the effects of pig (Sus scrofa) diets formulated with high-available-P corn and phytase on P levels in excreta and slurry stored for 30, 60, 90, 120, and 150 d. Twenty-four pigs (approximately 14 kg each) were fed one of four low-P diets: (i) normal corn, no phytase (control); (ii) normal corn with 600 phytase units kg(-1) (PHY); (iii) high-available-P corn, no phytase (HAP); and (iv) high-available-P corn with 600 phytase units kg(-1) (HAP + PHY). Fresh fecal and stored slurry dry matter (DM) was analyzed for total phosphorus (TP), dissolved molybdate-reactive phosphorus (DRP), dissolved organic phosphorus (DOP), acid-soluble reactive phosphorus (ASRP), acid-soluble organic phosphorus (ASOP), and phytate phosphorus (PAP). The PHY, HAP, and HAP + PHY diets significantly (alpha = 0.05) decreased fecal TP 19, 17, and 40%, respectively, compared with the control. Dissolved reactive P was 36% lower in the HAP + PHY diet compared with the other diets. Relative fractions (percent of TP) of DRP, DOP, ASOP, and PAP in slurry generally decreased with storage time up to 150 d, with the largest decreases occurring within 60 to 90 d. Diet-induced differences in relative fractions of DRP, DOP, ASRP, and PAP were significant when averaged across storage times, simulating a mixed-age slurry. Relative fractions of DRP in simulated mixed-age slurries were higher in HAP and HAP + PHY diets, indicating that diet may affect P losses under certain P-based application scenarios.

6-Phytase↗

PubMedDate not supplied

Partitioning and availability of uranium and nickel in contaminated riparian sediments.

The effects of iron oxides and organic matter on the partitioning and chemical lability of U and Ni were examined for contaminated riparian sediments from the U.S. Department of Energy's Savannah River Site. In sequential extractions of four sediments that ranged from 12.7 to 82.2 g kg(-1) in organic carbon, U was found almost exclusively in moderately labile fractions (93% in acid-soluble + organically bound). Nickel was distributed across all operationally defined fractions, including substantial amounts in the very labile fractions (4-15% in water-soluble + exchangeable), noncrystalline and crystalline iron oxides (38-49%), and in the nonlabile residual fraction (25-34%). Aqueous U concentrations in 1:1 sediment-water extracts were highly correlated to dissolved organic carbon (DOC) (R2 = 0.96; p < 0.0001) and ranged from 29 to 410 microg L(-1). Aqueous concentrations of Ni exceeded U by two to three orders of magnitude (124-2227 microg L(-1)) but were not correlated with DOC (R2 = 0.04; p = 0.53). Partitioning and solubility trends suggest that Ni availability is controlled primarily by iron-oxide phases, whereas U availability is dominated by naturally occurring organic carbon. Discrete mineral phases were also identified as nonlabile reservoirs of anthropogenic metals. In spite of comparably high sediment concentrations, Ni appears to be significantly more available than U in riparian sediments and therefore warrants greater consideration in terms of environmental consequences (i.e., transport, biological uptake, and toxicity).

Biological Availability↗

PubMed1983

Phosphorus: ruminal availability and effects on digestion.

The availability of P for ruminal digestion in vivo from a mono-dicalcium phosphate containing 21% P (mono-dical), a mono-dicalcium phosphate containing 18.5% P (dical), and defluorinated rock phosphate was compared with sodium phosphate (Na2HPO4 X 7H2O). Mono-dical, dical and defluorinated rock phosphate were found to be 88, 62 and 40% as available as sodium phosphate in the rumen. Compared with sodium phosphate, P from mono-dical, dical and defluorinated rock phosphate was 46.4, 28.8 and 2.5% as soluble in an in vitro ruminal buffer. In vitro P solubility in abomasal fluid increased with incubation time up to 1 h. Relative solubilities of the P sources at 1 h were 100, 71.6, 41.3 and 29.7% for sodium phosphate, mono-dical, dical and defluorinated rock phosphate, respectively. These sources can be solubilized in the abomasum and become available postruminally despite low solubility in the rumen. To determine the effect of P on ruminal and total tract digestion, diets low (.12%) and adequate (.23%) in P were fed to ruminally cannulated steers (700 kg) in a crossover design. Although higher ruminal P concentrations were detected with the high P diet than with the low P diet (398 vs 208 mg/liter), dry matter disappearance rate from nylon bags of ground corn, cotton duck or cottonseed hulls was unchanged. Estimated retention of P was higher (P less than .01) with the high P diet (8.3 g/d) than with the low P diet (1.0 g/d), but total tract digestibility was not enhanced significantly by added P. It appears that increasing ruminal P concentration from 208 to 398 mg/liter did not increase microbial cellulose digestion, but the low level was inadequate for maintaining the adult ruminant animal's P stores.

Animals↗

PubMed1985

Lysine availability in flash-dried blood meals for swine.

The available lysine content of three flash-dried blood meals was determined by use of a pig growth assay. Pigs that were 5 to 6 wk old were fed either one of the reference diets or one of the test diets for the 4-wk period of each assay. The reference diets were a corn-soybean meal basal (B) that was deficient in lysine, B+.1% L-lysine and B+.2% L-lysine. The test diets were B plus 1.5% and 3.0% of blood meal. The available lysine levels (percentage as fed) of ring-dried cattle blood meal, ring-dried swine blood meal and drum-dried cattle blood meal were determined to be 6.9, 7.4 and 6.7, respectively. All three flash-dried blood meals appeared to have similar available lysine levels and a value of 7% lysine may be used to formulate diets containing flash-dried blood meals. Incorporation of 3 or 6% drum-dried blood meal into starter diets improved N retention over a corn-soybean meal diet and did not reduce N-corrected metabolizable energy density of the diet.

Animal Feed↗

PubMed1996

The influence of different food components on the in vitro availability of iron, zinc and calcium from a composed meal.

The availability of iron, zinc and calcium from a composed meal was studied by an in vitro method using equilibrium dialysis after simulated gastric digestion. Four different concentrations of four influencing factors (coffee, vitamin C, wheat bran and pectin) were added to the mixed meal and their effect on the relative index of availability was studied after elemental analysis by atomic absorption spectrometry. Apart from ascorbic acid, all other factors had a negative effect on availability of minerals and trace elements. Most pronounced effect, and for all three elements, was observed for the addition of wheat bran. Zinc was the trace element, which was most sensitive to increased spiking of food constituents.

Ascorbic Acid↗