Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.

Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or previously treated mantle cell lymphoma. As the bioavailability of the acalabrutinib capsule (AC) depends on gastric pH for solubility and is impaired by acid-suppressing therapies, coadministration with proton-pump inhibitors (PPIs) is not recommended. Three studies in healthy subjects (N = 30, N = 66, N = 20) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of acalabrutinib maleate tablet (AT) formulated with pH-independent release. Subjects were administered AT or AC (orally, fasted state), AT in a fed state, or AT in the presence of a PPI, and AT or AC via nasogastric (NG) route. Acalabrutinib exposures (geometric mean [% coefficient of variation, CV]) were comparable for AT versus AC (AUCinf 567.8 ng h/mL [36.9] vs 572.2 ng h/mL [38.2], Cmax 537.2 ng/mL [42.6] vs 535.7 ng/mL [58.4], respectively); similar results were observed for acalabrutinib's active metabolite (ACP-5862) and for AT-NG versus AC-NG. The geometric mean Cmax for acalabrutinib was lower when AT was administered in the fed versus the fasted state (Cmax 255.6 ng/mL [%CV, 46.5] vs 504.9 ng/mL [49.9]); AUCs were similar. For AT + PPI, geometric mean Cmax was lower (371.9 ng/mL [%CV, 81.4] vs 504.9 ng/mL [49.9]) and AUCinf was higher (AUCinf 694.1 ng h/mL [39.7] vs 559.5 ng h/mL [34.6]) than AT alone. AT and AC were similar in BTK occupancy. Most adverse events were mild with no new safety concerns. Acalabrutinib formulations were comparable and AT could be coadministered with PPIs, food, or via NG tube without affecting the PKs or PDs.

Bioavailability of acalabrutinib suspension delivered via nasogastric tube in the presence or absence of a proton pump inhibitor in healthy subjects.

AIMS: Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Many critically ill patients are unable to swallow and need oral medications to be delivered via a nasogastric (NG) tube. Furthermore, critically ill patients are typically administered proton-pump inhibitors (PPIs) to prevent stress ulcers. Concomitant administration with PPIs reduces acalabrutinib exposure and is not currently recommended. To evaluate acalabrutinib in subjects co-administered with PPIs who require NG delivery, a phase 1, open-label, randomized, crossover, single-dose study was conducted in healthy subjects. METHODS: The study assessed the relative bioavailability of an acalabrutinib suspension-in regular, degassed Coca-Cola-administered via NG tube (Acala-NG) versus the pharmacokinetics (PK) of an acalabrutinib capsule administered orally with water. In addition, the PPI effect was evaluated by comparing the PK following Acala-NG in the presence or absence of rabeprazole. RESULTS: Exposure of acalabrutinib and its active metabolite (ACP-5862) were comparable following administration of Acala-NG versus the oral capsule (Geo mean ratio, % ref [90% confidence interval, CI]: acalabrutinib AUCinf : 103 [93-113]; Cmax : 144 [120-173]). In addition, exposure was similar following administration of Acala-NG with and without a PPI (Geo mean ratio, % ref [90% CI]: acalabrutinib AUCinf : 105 [79-138]; Cmax : 95 [66-137]). No safety or tolerability concerns were observed, and all adverse events were mild and resolved without treatment. CONCLUSIONS: Acala-NG with or without a PPI is safe and well-tolerated without impeding bioavailability.

The Role of 20-HETE, COX, Thromboxane Receptors, and Blood Plasma Antioxidant Status in Vascular Relaxation of Copper-Nanoparticle-Fed WKY Rats.

Recently, the addition of copper nanoparticles (NPs) in a daily diet (6.5 mg/kg) was studied in different animal models as a possible alternative to ionic forms. Male Wistar-Kyoto rats (24-week-old, n = 11) were fed with copper, either in the form of carbonate salt (Cu6.5) or metal-based copper NPs (NP6.5), for 8 weeks. The third group was fed with a half dose of each (NP3.25 + Cu3.25). The thoracic aorta and blood plasma was studied. Supplementation with NP6.5 decreased the Cu (×0.7), Cu/Zn-ratio (×0.6) and catalase (CAT, ×0.7), and increased Zn (×1.2) and superoxide dismutase (SOD, ×1.4). Meanwhile, NP3.25 + Cu3.25 decreased the Cu/Zn-ratio (×0.7), and CAT (×0.7), and increased the daily feed intake (×1.06). Preincubation with either the selective cyclooxygenase (COX)-2 inhibitor, or the non-selective COX-1/2 inhibitor attenuated vasodilation of rat thoracic aorta in the NP6.5 group exclusively. However, an increased vasodilator response was observed in the NP6.5 and NP3.25 + Cu3.25 group of rats after preincubation with an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation, and the thromboxane receptor (TP) antagonist. Significant differences were observed between the NP6.5 and NP3.25 + Cu3.25 groups of rats in: dietary intake, acetylcholine-induced vasodilation, and response to COX-inhibitors. Copper NPs in a standard daily dose had more significant effects on the mechanism(s) responsible for the utilization of reactive oxygen species in the blood plasma with the participation of prostanoids derived from COX-2 in the vascular relaxation. Dietary copper NPs in both doses modified vasodilation through the vasoconstrictor 20-HETE and the TP receptors.

The Effect of Hemp (Cannabis sativa L.) Seeds and Hemp Seed Oil on Vascular Dysfunction in Obese Male Zucker Rats.

Seeds of industrial hemp (Cannabis sativa L.) contain a large amount of protein (26.3%), dietary fiber (27.5%), and fatty acids (33.2%), including linoleic, α-linolenic, and some amount of γ-linolenic acid. In our study, obese male Zucker rats (n = 6) at 8 weeks of age were supplemented for a further 4 weeks with either ground hemp seeds (12% diet) or lipid fractions in the form of hemp seed oil (4% diet). Hemp oil decreased blood plasma HDL-cholesterol (x0.76, p ≤ 0.0001), triglycerides (x0.55, p = 0.01), and calculated atherogenic parameters. Meanwhile, hemp seeds decreased HDL-cholesterol (x0.71, p ≤ 0.0001) and total cholesterol (x0.81, p = 0.006) but not the atherogenic index. The plasma antioxidant capacity of water-soluble compounds was decreased by the seeds (x0.30, p = 0.0015), which in turn was associated with a decrease in plasma uric acid (x0.18, p = 0.03). Dietary hemp seeds also decreased plasma urea (x0.80, p = 0.02), while the oil decreased the plasma total protein (x0.90, p = 0.05). Hemp seeds and the oil decreased lipid peroxidation in the blood plasma and in the heart (reflected as malondialdehyde content), improved contraction to noradrenaline, and up-regulated the sensitivity of potassium channels dependent on ATP and Ca2+. Meanwhile, acetylcholine-induced vasodilation was improved by hemp seeds exclusively. Dietary supplementation with ground hemp seeds was much more beneficial than the oil, which suggests that the lipid fractions are only partially responsible for this effect.

Strawberry phenolic extracts effectively mitigated metabolic disturbances associated with high-fat ingestion in rats depending on the ellagitannin polymerization degree.

In the present experiment it was hypothesised that dietary strawberry ellagitannin-rich extracts would mitigate negative consequences associated with consumption. Therefore, two extracts rich in dimeric (D-ET) or monomeric (M-ET) ellagitannins (ETs) were added to a standard or high-fat diet fed to rats for four weeks. The D-ET-rich extract contained 82.3% polyphenols, and the M-ET/D-ET ratio was 40 : 60, while the M-ET-rich extract contained 88.0% and 96 : 4, respectively. The experimental feeding with high-fat diets containing extracts resulted in beneficial mitigating effects in the lipid profile, redox status of the rat's liver and blood plasma. According to the accepted hypothesis, the obtained results pointed at increased desired hepatic and plasma modifications when the extract was rich in M-ET, as indicated by favourable changes in the hepatic fat content, GSH and GSSG concentrations and GSH/GSSG ratio as well as blood plasma FRAP, ACL, HDL-cholesterol, and atherogenic coefficient values. These changes were partly connected to the fact that M-ET was more prone vs. D-ET to intestinal microbial conversion into respective metabolites. The urinary daily excretion of ET metabolites and their blood plasma concentrations were higher in rats fed with M-ET vs. D-ET-rich diets. To conclude, the metabolic action of the M-ET-rich extract in the normalization of high-fat-induced disturbances was more pronounced.

The composition and vascular/antioxidant properties of Taraxacum officinale flower water syrup in a normal-fat diet using an obese rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum officinale (L.), commonly called dandelion has been used for centuries as a natural medicine to treat inflammatory diseases including some metabolic alterations associated with obesity. AIM OF THE STUDY: Based on animal experiments this study aims to explore the potential mechanisms of action of T. officinale flower water syrup (TOFS) together with a normal-fat diet in the intervention of obesity. MATERIALS AND METHODS: Obese male albino-Wistar rats (n = 8) at 25 weeks of age were fed with a normal-fat diet with or without added 27.82% TOFS (w/w) for 4 weeks. The reactivity of thoracic aorta and antioxidant capacity were studied. RESULTS: TOFS delivered daily 926.8 µg of L-chicoric acid, 20.19 µg of luteolin and 3.379 ‬g of sucrose. TOFS showed beneficial effects by regulating blood lipids (HDL, x1.11-fold increase), thereby lowering the risk factors for atherosclerosis (TC/HDL, x0.90-fold). The antioxidant status was improved via an increase in plasma superoxide radical scavenging (SOD, x1.6-fold) and a decrease in lipid peroxidation (MDA, x0.81-fold). Moreover, the following were decreased: Cu (x0.53-fold), Zn (x0.72-fold) and the Cu/Zn molar ratio (x0.60-fold). A marker for liver damage/disease was beneficially decreased (ALP, x0.87-fold). TOFS modulated in a significant way COX-depended relaxation to ACh (p = 0.05) but not to CORM-2 (p = 0.1651) in isolated thoracic arteries, by decreased participation of vasoconstrictor prostanoids. The vascular contraction to prostaglandin F2α was also decreased (x0.62-fold). We observed no change in the feed intake, body weight, organ-to-body weight ratio, blood glucose, CAT, FRAP, AST, ALT, TBARS/carbonyls (in heart, liver, kidneys, spleen) and carbonyls (in blood plasma, thoracic arteries); as well as F2-isoprostanes in urine. Vascular response to the vasodilators ACh, SNP, A23187, CORM-2, pinacidil, NS-1619 and to the vasoconstrictors NA, U-46619, ET-1 as well as hyperpolarizing mechanism(s) were not modified. CONCLUSIONS: TOFS possesses beneficial properties by regulating prostanoids and antioxidant status.

Protective Effects of a Strawberry Ellagitannin-Rich Extract against Pro-Oxidative and Pro-Inflammatory Dysfunctions Induced by a High-Fat Diet in a Rat Model.

Due to the demonstrated intestinal microbial transformation of strawberry ellagitannins (ET) into bioactive metabolites, in the current study on rats, we hypothesised that the dietary addition of a strawberry ET-rich extract (S-ET) to a high-fat diet (HFD) would attenuate disturbances in the redox and lipid status as well as in the inflammatory response. We randomly distributed 48 Wistar rats into six groups and used two-way analysis of variance (ANOVA) to assess the effects of two main factors-diet type (standard and high-fat) and ET dosage (without, low, and 3× higher)-applied to rats for 4 weeks. In relation to the hypothesis, irrespective of the dosage, the dietary application of ET resulted in the desired attenuating effects in rats fed a HFD as manifested by decreased body weight gain, relative mass of the epididymal pad, hepatic fat, oxidized glutathione (GSSG), triglycerides (TG), total cholesterol (TC), and thiobarbituric acid-reactive substances (TBARS) concentrations as well as desired modifications in the blood plasma parameters. These beneficial changes were enhanced by the high dietary addition of ET, which was associated with considerably higher concentrations of ET metabolites in the urine and plasma of rats. The results indicated that S-ET could be effectively used for the prevention and treatment of metabolic disturbances associated with obesity, dyslipidaemia, redox status imbalance, and inflammation.

The Characterization of Ground Raspberry Seeds and the Physiological Response to Supplementation in Hypertensive and Normotensive Rats.

This study aimed to evaluate the protective role of ground raspberry seeds (RBS) as a source of polyphenols and essential fatty acids on blood plasma enzymatic antioxidant status, lipid profile, and endothelium-intact vasodilation during physiological and pathological conditions. Young normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) at ten weeks of age were fed with either a control diet or were supplemented with added 7% RBS for six weeks (n = 6). The main component of RBS was dietary fiber (64%) and the main polyphenols were ellagitannins (1.2%) and flavan-3-ols (0.45%). Irrespective of the rat model, ground RBS decreased liver enzyme aspartate aminotransferase (0.9-fold) and hydrogen peroxide scavenging capacity (Catalase, 0.9-fold). In supplemented SHRs, preincubation with inducible nitric oxide synthase (iNOS) inhibitor 1400W, nonselective cyclooxygenase (COX) inhibitor indomethacin, selective COX-2 inhibitor NS-398, prostacyclin (PGI2) synthesis inhibitor tranylcypromine (TCP), thromboxane receptor (TP) antagonist SQ-29548, thromboxane synthesis inhibitor furegrelate, and 20-HETE synthesis inhibitor HET0016 induced the same relaxant response to acetylcholine as in the nonsupplemented control group. In supplemented WKYs, atherogenic index was decreased (0.8-fold), while iNOS and COX-2-derived PGI2 increased acetylcholine-induced vasodilation. These effects of ground RBS may constitute a potential mechanism for preventing cardiovascular diseases.

Resveratrol modulates the blood plasma levels of Cu and Zn, the antioxidant status and the vascular response of thoracic arteries in copper deficient Wistar rats.

Copper (Cu) deficiency plays an important role in the development of cardiovascular disorders. Resveratrol (RSV) possesses pleiotropic cardiovascular benefits; however, the mechanism(s) by which RSV exerts protective effects are not completely understood. Male Wistar rats at 6 weeks of age were fed for 8 weeks with a Cu deficient diet (no added Cu, Cu = 0). In addition, Cu deficient rats were supplemented with RSV (500 mg/kg of diet, n = 9). Blood and intestinal samples were taken for further analysis together with internal organs and thoracic arteries. RSV supplementation resulted in elevated blood plasma levels of Cu (x2.1) and Zn (x1.1), in an increased activity of superoxide dismutase (SOD, x1.5) and ferric reducing antioxidant power (FRAP, x1.2). Meanwhile, markers of lipid peroxidation expressed as malondialdehyde (MDA, x1.5) and lipid hydroperoxides (LOOH, x1.1) were also increased in a significant way. Food intake, body weight, blood glucose, catalase, ceruloplasmin, lipid profile and intestinal samples were not modified. RSV enhanced the vasoconstriction of isolated thoracic arteries to noradrenaline (x1.4), potentiated the vasodilation to acetylcholine (ACh, x1.4) and increased the sensitivity to sodium nitroprusside (SNP). In addition, preincubation with the cyclooxygenase (COX)-inhibitor, indomethacin, potentiated the ACh-induced vasodilation, which was more pronounced in animals not supplemented with RSV. The KATP channel opener, pinacidil, induced a similar response in both studied groups. In conclusion, this study demonstrates that RSV supplementation influences oxidative stress and the antioxidant status, which may modify the vascular response in Cu deficiency.

The cytokine alterations/abnormalities and oxidative damage in the pancreas during hypertension development.

The aim of the present study was to compare the content of cytokines, chemokines, and oxidative stress markers in the pancreas of spontaneously hypertensive rats (SHRs) and Wistar Kyoto Rats (WKYs) serving as controls. Enzyme-like immunosorbent assay (ELISA) and biochemical methods were used to measure pancreatic levels of interleukin-1ß, interleukin-6, tumor necrosis factor α, transforming growth factor ß, RANES, monocyte chemoattractant protein 1, interferon gamma-induced protein 10, malondialdehyde, and sulfhydryl groups. The results showed that the pancreatic concentrations of all studied cytokines and chemokines did not differ between 5-week-old SHRs and WKYs, except RANTES which was significantly reduced in juvenile SHRs. In 10-week-old animals, except interleukin-1ß, the levels of all these proteins were significantly reduced in SHRs. The pancreatic levels of malondialdehyde were significantly reduced in 5-week-old SHRs and significantly elevated in 10-week-old SHRs while the contents of sulfhydryl groups were similar in both rat strains at any age studied. In conclusion, these data provide evidence that in maturating SHRs, the pancreatic levels of cytokines and chemokines are significantly reduced, while malondialdehyde significantly elevated. This suggests that in the pancreas of mature SHRs, the inflammation process is suppressed but there is ongoing oxidative damage.

Copper nanoparticles modify the blood plasma antioxidant status and modulate the vascular mechanisms with nitric oxide and prostanoids involved in Wistar rats.

BACKGROUND: We aimed to analyze whether a diet supplemented with a standard dose of copper (Cu) in the form of nanoparticles, as an alternative to carbonate, exerts beneficial effects within the vasculature and improves the blood antioxidant status. METHODS: Male Wistar rats were fed for 8 weeks with a diet supplemented with Cu (6.5 mg Cu/kg in the diet) either as nanoparticles (40 nm diameter) or carbonate - the control group. Moreover, a negative control was not supplemented with Cu. At 12 weeks of age, blood samples, internal organs and thoracic aorta were taken for further analysis. Blood antioxidant mechanism was measured together with Cu and Zn. RESULTS: Diet with Cu as nanoparticles resulted in an elevated catalase activity and ferric reducing ability of plasma, however decreased Cu (plasma), and ceruloplasmin (Cp) compared to carbonate. The participation of vasoconstrictor prostanoid was increased, as indomethacin did not modify the acetylcholine (ACh)-induced response. Arteries from Cu nanoparticle and carbonate rats exhibited a reduced maximal contraction to potassium chloride and an increased response to noradrenaline. The endothelium-dependent vasodilation to ACh was enhanced while exogenous NO donor, sodium nitroprusside, did not modify the vascular response. Down-regulation of BKCa channels influenced hyperpolarizing mechanism. The superoxide dismutase and HDL-cholesterol were decreased opposite to an increased lipid hydroperoxides, malondialdehyde, Cu (plasma and liver) and Cp. CONCLUSION: Despite the increased antioxidant capacity in blood of Cu nanoparticle fed rats, vasoconstrictor prostanoids and NO are involved in vascular regulation.

Toxicity and cardiac effects of acute exposure to tryptophan metabolites on the kynurenine pathway in early developing zebrafish (Danio rerio) embryos.

Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of exposure to tryptophan metabolites might impact the early development of organism. Thus, this study examined the effects of KP exposure in zebrafish embryos starting at the blastula period (4hpf) and the segmentation stage (24hpf). 24-hour EC50 and LC50 values were determined in 4hpf embryos as: 26.74 and 331.6µM for anthranilic acid (AA), 62.88 and 616.4µM for quinolinic acid (QUIN), and EC50 - 96.10µM for picolinic acid (PA) and LC50 - 400µM in kynurenic acid (KYNA). In addition, treatment with nanomolar concentrations of KYNA (50nM, 48 and 72hpf embryos) caused a dose-dependent increase in heartbeat. The increase was also seen with l-kyn treatment (50µM, 72hpf), which was the opposite of other applied l-kyn metabolites. A significant drop in heartbeat was observed after a 20-min acute exposure to 626µM PA, 594µM XA and 499µM QUIN, and complete recovery was seen only when PA had been removed. Concentrations of KP metabolites reached in people with different pathological conditions did not exert toxicity to zebrafish embryos and seems to be safe for developing embryos and therefore, the risk of developing impairments in pregnancy of women carrying KP-associated pathologies is initially low.

Patients with infective endocarditis: Five-year observation from a single reference center.

BACKGROUND: Infective endocarditis (IE) is a serious and, if untreated, usually fatal disease. Diagnosing IE is often considered to be one of the most difficult medical conditions because of the heterogeneous and ambiguous clinical presentation. OBJECTIVES: The purpose of this study was to investigate diagnostic and therapeutic management in a non-selected group of patients with IE. MATERIAL AND METHODS: A total of 45 patients consecutively admitted to the Department of Cardiology, Medical University of Silesia in Katowice (mean age 53.6 ±18 years; 13 females) with IE between 2009 and 2013 were evaluated. Echocardiography, blood cultures and laboratory tests were performed on every patient upon admission. An analysis of the diagnostic and therapeutic management was performed. RESULTS: Most frequent predisposing factors were: a history of heart valve replacement and/or repair (40%), dental caries (17.8%) and bicuspid aortic valve (17.8%). The majority of patients were admitted from another hospital (91.1%). Fever (92%) and symptoms of heart failure (80%) were the most common manifestations. Abnormalities in ECG occured in 91.2% of patients. Echocardiography was highly sensitive (>90%) in detecting endocardial changes. Staphylococcal etiology was the most common (33.3%). Surgery procedures were necessary in 62.2% of patients. Arrhythmias (91.1%) and acute heart failure (57.8%) were the most commonly observed complications, although 24.4% of subjects had neurological disorders. The patients studied were burdened with a number of factors predisposing to IE. CONCLUSIONS: The diagnosis of IE can be a difficult challenge. Particular attention should be paid to the care of oral hygiene and treatment of dental diseases in order to reduce the risk of IE developing.

The Influence of Resiniferatoxin (RTX) and Tetrodotoxin (TTX) on the Distribution, Relative Frequency, and Chemical Coding of Noradrenergic and Cholinergic Nerve Fibers Supplying the Porcine Urinary Bladder Wall.

The present study investigated the influence of intravesically instilled resiniferatoxin (RTX) or tetrodotoxin (TTX) on the distribution, number, and chemical coding of noradrenergic and cholinergic nerve fibers (NF) supplying the urinary bladder in female pigs. Samples from the bladder wall were processed for double-labelling immunofluorescence with antibodies against cholinergic and noradrenergic markers and some other neurotransmitter substances. Both RTX and TTX caused a significant decrease in the number of cholinergic NF in the urinary bladder wall (in the muscle coat, submucosa, and beneath the urothelium). RTX instillation resulted in a decrease in the number of noradrenergic NF in the submucosa and urothelium, while TTX treatment caused a significant increase in the number of these axons in all the layers. The most remarkable changes in the chemical coding of the NF comprised a distinct decrease in the number of the cholinergic NF immunoreactive to CGRP (calcitonin gene-related peptide), nNOS (neuronal nitric oxide synthase), SOM (somatostatin) or VIP (vasoactive intestinal polypeptide), and an increase in the number of noradrenergic NF immunopositive to GAL (galanin) or nNOS, both after RTX or TTX instillation. The present study is the first to suggest that both RTX and TTX can modify the number of noradrenergic and cholinergic NF supplying the porcine urinary bladder.

Variations of niacin content in saltwater fish and their relation with dietary RDA in Polish subjects grouped by age.

INTRODUCTION: A rich and natural source of readily assimilated dietary protein together with invaluable vitamins and minerals are fish, particularly the saltwater species. The quality of any given foodstuff is determined by its nutritional value, which in turn depends on the food type and methods used for manufacture, processing and storage. Many fish products contain fewer water soluble vitamins than the source foodstuff as a result of using various technologies during food processing, such as smoking or deep freezing, where vitamins are often either degraded or leached out. In the case of niacin it is relatively easy to make good such losses by eating niacin-rich foods or by taking dietary supplements e.g. the essential amino acid L-tryptophan. OBJECTIVES: To determine niacin content in sea fish that are commonly available on the Polish market and to assess whether this dietary source is sufficient to satisfy the RDA requirements for various age groups of selected subjects living in Poland. MATERIAL AND METHODS: Niacin levels were measured firstly in 10 saltwater fish species together with butterfish and Norwegian salmon that formed a separate group. Altogether, 15 types of fish products were analysed in all. They consisted of smoked fish: whitefish, butterfish, sprat, trout, herring (kippers) and mackerel, and frozen fish: butterfish, Norwegian salmon, sole, grenadier and panga. Each product was measured as ten replicates, thus in total 150 analyses were performed. A microbiologically-based method was used for the niacin determination, with enzyme hydrolysis by 40 mg papain and diastase on a 2 g sample (according to the AOAC procedure) to release the free form from the bioavailable form that is bound to NAD and NADP. RESULTS: The most plentiful sources of niacin were found in smoked fish with the highest amounts in butterfish, after warm temperature smoking, and in mackerel; respectively 9.03 and 8.90 mg/100 g. Such 100 g portions of smoked fish are a good dietary source of niacin, in that for men and women above 19 years of age, they constitute respectively 22% - 56% and 25% - 64% of the RDA (Recommended Daily Allowance). The highest levels of niacin in frozen fish were found in butterfish and Norwegian salmon; respectively 8.05 and 5.75 mg/100 g which in turn represent respectively 10% - 50% and 11% - 56% of the RDA in men and women aged above 19 years. CONCLUSIONS: Niacin concentrations varied according to fish species. The richest dietary sources were smoked fish consisting of butterfish, after warm temperature smoking, and mackerel. In frozen fish, butterfish and Norwegian salmon had the highest niacin amounts. A 100 g serving of such sea fish can, to quite a large extent, satisfy the adult RDA.

Allium sativum: facts and myths regarding human health.

Garlic (Allium sativum L. fam. Alliaceae) is one of the most researched and best-selling herbal products on the market. For centuries it was used as a traditional remedy for most health-related disorders. Also, it is widely used as a food ingredient--spice and aphrodisiac. Garlic's properties result from a combination of variety biologically active substances which all together are responsible for its curative effect. The compounds contained in garlic synergistically influence each other so that they can have different effects. The active ingredients of garlic include enzymes (e.g. alliinase), sulfur-containing compounds such as alliin and compounds produced enzymatically from alliin (e.g. allicin). There is a lot of variation among garlic products sold for medicinal purposes. The concentration of Allicin (main active ingredient) and the source of garlic's distinctive odor depend on processing method. Allicin is unstable, and changes into a different chemicals rather quickly. It's documented that products obtained even without allicin such as aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement, treatment of cardiovascular diseases, cancer, liver and other areas. Some products have a coating (enteric coating) to protect them against attack by stomach acids. Clinically, garlic has been evaluated for a number of purposes, including treatment of hypertension, hypercholesterolemia, diabetes, rheumatoid arthritis, cold or the prevention of atherosclerosis and the development of tumors. Many available publications indicates possible antibacterial, anti-hypertensive and anti-thrombotic properties of garlic. Due to the chemical complexity of garlic and the use of different processing methods we obtain formulations with varying degrees of efficacy and safety.