Design and implementation of an online tool for managing the availability of high-cost perishable medicines.

Introduction: Due to their impact on healthcare systems, the sustainability and optimization of high-cost drugs is an issue of concern for several countries. Different strategies have been implemented such as centralized purchasing to optimize budgetary resources. However, there is still a need for a mechanism to optimize these drugs further.

Cytological and bacteriological sampling from filters used for embryo recovery to evaluate the uterine status of donor mares.

While testing for uterine bacterial infection is usually performed prior to artificial insemination (AI), samples taken during or after embryo flushing are generally not assessed either in subfertile and old mares or in fertile mares, even though knowledge of the status of the uterine environment in which the embryo is to develop would help to predict the outcome of embryo transfer programmes. The presence of bacteria and inflammatory cells in the liquid retained in the filter after uterine flushing in donors was determined at the moment of embryo recovery. Primarily, a group of mares (n = 8) displaying evident clinical signs of endometritis was selected to evaluate the cytological and bacteriological findings in filters after uterine flushing and in uterine cotton swabs.

Nitrosative deamination of 2'-deoxyguanosine and DNA by nitrite, and antinitrosating activity of β-carboline alkaloids and antioxidants.

Endogenous and dietary nitrite produces reactive nitrogen species (RNS) that react with DNA causing mutations. The nitrosation of 2'-deoxyguanosine (dGuo) and DNA with nitrite was studied under different conditions, and the reaction and degradation products identified and analysed by HPLC-DAD-MS. Nitrosative deamination of dGuo produced xanthine along with 2'-deoxyxanthosine whereas DNA afforded xanthine.

Hydroxyl radical reactions and the radical scavenging activity of β-carboline alkaloids.

β-Carbolines are bioactive pyridoindole alkaloids occurring in foods, plants and the human body. Their activity as hydroxyl radical (OH) scavengers is reported here by using three different methods: deoxyribose degradation, hydroxylation of benzoate and hydroxylation of 2'-deoxyguanosine to give 8-hydroxy-2'-deoxyguanosine (8-OHdG) as assessed by RP-HPLC (MS). Fenton reactions (Fe(2+)/Fe(3+) plus H2O2) were used for OH generation, and the radical increased in the presence of ascorbic acid or 6-hydroxydopamine as pro-oxidants.

Naturally-occurring tetrahydro-β-carboline alkaloids derived from tryptophan are oxidized to bioactive β-carboline alkaloids by heme peroxidases.

β-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-β-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-β-carbolines (i.

Metabolite profile resulting from the activation/inactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-methyltetrahydro-β-carboline by oxidative enzymes.

Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) neurotoxin and its naturally occurring analogs 2-methyltetrahydro-β-carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO), cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase), were investigated and compared. The metabolite profile differed among the enzymes investigated.

Simultaneous generation of second to fifth harmonic conical beams in a two dimensional nonlinear photonic crystal.

Broadly tunable multiple high-harmonic conical beams have been generated by means of a multistep χ cascade processes in a two dimensional nonlinear photonic crystal. The nonlinear structure consists of a square lattice of inverted hexagonal domains with diameters and distances between domains as low as 1 μm. The large number of reciprocal lattice vectors provided by both the square nonlinear structure and the hexagonal shaped domains, along with imperfections on the size and shape of the individual domains make possible the simultaneous generation of second up to fifth harmonic conical beams in a single nonlinear structure by using different types of phase matching geometries.

Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine.

The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue.

N-methyltetrahydro-beta-carboline analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin are oxidized to neurotoxic beta-carbolinium cations by heme peroxidases.

2-Methyl-1,2,3,4-tetrahydro-beta-carboline (2-Me-THbetaC) and 2,9-dimethyl-1,2,3,4-tetrahydro-beta-carboline (2,9-diMe-THbetaC) are naturally occurring analogs of the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas their corresponding aromatic 2-methyl-beta-carbolinium cations resemble 1-methyl-4-phenylpyridinium (MPP(+)) and are considered potential toxins involved in Parkinson's disease (PD). To become toxicants, 2-methyltetrahydro-beta-carbolines need to be oxidized (aromatized) by human metabolic enzymes to pyridinium-like (beta-carbolinium) cations as occur with MPTP/MPP(+) model. In contrast to MPTP, human MAO-A or -B were not able to oxidize 2-Me-THbetaC to pyridinium-like cations.

Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay.

Indoles are very common in the body and diet and participate in many biochemical processes. A total of twenty-nine indoles and analogs were examined for their properties as antioxidants and radical scavengers against 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS*+ radical cation. With only a few exceptions, indoles reacted nonspecifically and quenched this radical at physiological pH affording ABTS.

Tetrahydro-beta-carboline alkaloids occur in fruits and fruit juices. Activity as antioxidants and radical scavengers.

Tetrahydro-beta-carbolines are biologically active alkaloids that occur and accumulate in mammalian tissues, fluids, and brain, but their ultimate origin or biological role is still uncertain. Four tetrahydro-beta-carboline alkaloids: 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 1-methyl-1,2,3,4-tetrahydro-beta-carboline, and 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline, are found as naturally occurring substances in some fruit and fruit juices. These compounds occur in the microg/g level in those products, and a characteristic and distinct profile appears to exist depending on the type of fruit and juice involved.

L-tryptophan reacts with naturally occurring and food-occurring phenolic aldehydes to give phenolic tetrahydro-beta-carboline alkaloids: activity as antioxidants and free radical scavengers.

The reaction between the essential amino acid l-tryptophan and flavoring or naturally occurring phenyl and phenolic aldehydes was studied, and the alkaloidal reaction products were characterized by NMR and HPLC-MS. Benzaldehyde, vanillin, syringaldehyde, salicylaldehyde, and anisaldehyde condensed with l-tryptophan in aqueous-acidic media affording the corresponding phenolic tetrahydro-beta-carboline-3-carboxylic acid as two diastereoisomers, 1S,3S-cis and 1R,3S-trans. With the exception of benzaldehyde, the rest of the aldehydes needed heating conditions (70 degrees C) to significantly form tetrahydro-beta-carbolines over time with the cyclization highly favored at low pH.

Tetrahydro-beta-carboline alkaloids that occur in foods and biological systems act as radical scavengers and antioxidants in the ABTS assay.

Tetrahydro-beta-carboline alkaloids that occur in foods such as wine, seasonings, vinegar and fruit products juices, jams) acted as good radical scavengers (hydrogen- or electron donating) in the ABTS (2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) assay, and therefore, they could contribute to the beneficial antioxidant capacity attributed to foods. In contrast, the fully aromatic beta-carbolines norharman and harman did not show any radical scavenger activity in the same assay. During the reaction with ABTS.

Identification and occurrence of the novel alkaloid pentahydroxypentyl-tetrahydro-beta-carboline-3-carboxylic acid as a tryptophan glycoconjugate in fruit juices and jams.

The novel carbohydrate-derived beta-carboline, 1-pentahydroxypentyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, was identified in fruit- and vegetable-derived products such as juices, jams, and tomato sauces. This compound occurred as two diastereoisomers, a cis isomer (the major compound) and a trans isomer, ranging from undetectable amounts to 6.5 microg/g.