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Analysis of cyanide using fluorogenic derivatization and capillary electrophoresis.

Samples containing cyanide were incubated at 85 °C in the presence of the fluorogenic reagent 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and glutamic acid, and analyzed by capillary electrophoresis utilizing post-separation laser-induced fluorescence detection in a sheath flow cuvette. The separation time on a 25 cm long capillary at 800 Vcm-1 was 3 min with the fluorescent product eluting at 107 s. Flushing of the capillary was not required between runs. Signal was proportional with cyanide concentration from 50 nM to 1.5 μM. LOD and LOQ were determined to be 26 and 87 nM respectively. As an

The kynurenine pathway storm in epilepsy: mechanisms and therapeutic implications.

The kynurenine pathway (KP) is the main route for tryptophan (TRP) degradation and plays a crucial role in neuroinflammation, oxidative stre … of the KP, specifically manifested as a decrease in kynurenic acid (KYNA) level and an increase in quinolinic acid (QA) level. The IDO-mediated shift of TRP metabolism towards the KP is established as a critical mechanism underlying depression comorbidity in epilepsy. Therapeutic modulation of this pathway, through targeting key enzymes like IDO and restoring th …

The Role of the Kynurenine Pathway in Irreversible Pulpitis.

Current therapeutic practices have limited effectiveness at targeting acute pain locally. This is in part due to the lack of understanding o … increased IDO may direct the KYN pathway toward the generation of the neuroinflammatory catabolite quinolinic acid, a metabolite that is opposite to the production of neuroprotective kynurenic acid. Administration of OLCs with ODN 2006 in vitro induced changes similar to those developed in SIP induced by bacterial infection. To our knowledge, this article is the …

Central and Peripheral Characterization of Key Kynurenine Pathway Metabolites in Mexican Patients with Multiple Sclerosis: An Exploratory Study.

Background/Objectives: Multiple Sclerosis (MS) is a chronic immune-mediated disorder characterized by neuroinflammation and neurodegeneratio … ic acid (KYNA) and 3-hydroxykynurenine (3-HK), as well as cerebrospinal fluid (CSF) levels of KYNA, quinolinic acid (QUIN), interleukin-4 (IL-4), and interleukin-6 (IL-6), were determined in treatment-naïve relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and treated PMS patients. Serum levels were compared with those of healthy controls, and CSF fin …

Sildenafil, alone and in combination with imipramine or escitalopram, display antidepressant-like effects in an adrenocorticotropic hormone-induced (ACTH) rodent model of treatment-resistant depression.

BACKGROUND: Major depressive disorder (MDD) represents a challenge with high prevalence and limited effectiveness of existing treatments, pa … els of brain-derived neurotrophic factor (BDNF), serotonin, norepinephrine, kynurenic acid (KYNUA), quinolinic acid (QUINA), and glutathione. The various mono- and combined treatments significantly reversed some of these changes, whereas IMI-15 + SIL-10 significantly increased glutathione disulfide levels. ESC-15 + SIL-3 significantly reduced plasma corticosteron …

The neurotoxic branch of the kynurenine pathway is highly activated in the central nervous system of patients with pneumococcal meningitis.

BACKGROUND: Acute bacterial meningitis (ABM) causes excessive activation of N-methyl-D-aspartate receptors (NMDAr), leading to cortical and … VM) meningitis, the cerebrospinal fluid (CSF) concentrations of TRP, KYN, kynurenic acid (KYNA) and quinolinic acid (QUINA) were evaluated by ultra-high performance liquid chromatography (uHPLC) coupled to mass spectrometry. In addition, CSF levels of IL-6, IL-10 and TNF-α were quantified by multi-analyte flow assay. The data was mined and integrated using statis …

Genetic Analysis of Tryptophan Metabolism Genes in Sporadic Amyotrophic Lateral Sclerosis.

The essential amino acid tryptophan (TRP) is the initiating metabolite of the kynurenine pathway (KP), which can be upregulated by inflammatory conditions in cells. Neuroinflammation-triggered activation of the KP and excessive production of the KP metabolite quinolinic acid are common features of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In addition to its role in the KP, genes involved in TRP metabolism, including its incorporation into proteins, and synthesis of the neurotransmitter serotonin, have also been genetically and functionally linked to th…

Periodontal inflammation and tryptophan-kynurenine metabolism in Parkinson's disease.

OBJECTIVE: The kynurenine pathway(KP) of tryptophan catabolism is a major regulator of the immune response. Metabolites of this pathway may … , kynurenine, kynurenine/tryptophan ratio, kynurenic acid, 3-hydroxykynurenine, picolinic acid, and quinolinic acid, were quantified using liquid chromatography–mass spectrometry. Periodontal status was assessed by recording plaque index, probing pocket depth, clinical attachment loss, and bleeding on probing according to standard clinical procedures. RESULTS: Cl …

Регулирование Kynurenin Pathway в Relapping Rising Multial Sclerosis и его корреляции с прогрессивным нейродегенерацией.

Несмотря на отсутствие острых повреждений при многократном склерозе (MS), хроническое нейродегенерация продолжает развиваться, и потенциальным основополагающим механизмом может быть кинурайнский путь (КП). Как известно, продолжительная активация КП от хронического воспаления усугубляет прогресс нервно-дегенеративных заболеваний за счет производства нейротоксичных метаболитов. В числе 8 КП метаболиты, six из них, а именно: кинурень (КИН), 3- Гидроксилкилинин (3ГК), антраиличная кислота (АА), кинуриновая кислота (КИНА) и квинолинская кислота (QUIN) были связаны с нейродегенерацией.Чтобы получить

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to p … ely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration. METHODS: To gain insights into the links between the KP and neurodegeneration in MS, we investigated the KP metabolomics profile of relapsing remitting MS (RRMS) patients and their correlation wi …

The association between inflammation and kynurenine pathway metabolites in electroconvulsive therapy for schizophrenia: Implications for clinical efficacy.

The kynurenine pathway (KP) of tryptophan has been implicated in the pathogenesis of schizophrenia and its interaction with the immune syste … renia patients had lower levels of Tryptophan (TRP), N-formylkynurenine (NFK), xanthinic acid (XA), quinolinic acid (QA), kynurenic acid (KYNA), KYNA/KYN and QA/KYNA, but higher levels of IL-18 mRNA, KYN/TRP compared to healthy controls (all p < 0.05). After electroconvulsive therapy (ECT), patients with low inflammation achieved better clinical improvement (PANS …

The Usefulness of the Low-FODMAP Diet with Limited Tryptophan Intake in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome.

(1) Background: A low-FODMAP diet is often recommended in the treatment of irritable bowel syndrome, but it does not improve abdominal sympt … d its metabolites: 5-hydoxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were measured in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). (3) Results: The consumption of TRP per mg/kg/b.w./24 h has decreased in Group IIA from 20.9 ± 2.39 to 17.45 ± 2.41 (16.5%) and in Group IIB from 21.3 ± 2.3 …

Systemic and central nervous system metabolic alterations in Alzheimer's disease.

BACKGROUND: Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfuncti … l amino acids were associated with CSF Amyloidβ1-42. The tryptophan catabolites, kynurenic acid and quinolinic acid, showed significantly higher concentrations in CSF of AD patients, which, together with other tryptophan pathway intermediates, were correlated with either CSF Amyloidβ1-42, or tau and phosphorylated Tau-181. CONCLUSIONS: This study revealed AD-ass …

Hybrids of Cinchona Alkaloids and Bile Acids as Antiparasitic Agents Against Trypanosoma cruzi.

The current chemotherapy of Chagas disease needs to be urgently improved. With this aim, a series of 16 hybrids of Cinchona alkaloids and bile acids were prepared by functionalization at position C-2 of the quinoline nucleus by a radical attack of a norcholane substituent via a Barton-Zard decarboxylation reaction. The antitrypanosomal activity of the hybrids was tested on different stages and strains of T. cruzi. In particular, eight out of 16 hybrids presented an IC50 ≤1 μg/mL against trypomastigotes of the CL Brener strain and/or a selectivity index higher than 10. These promising hybrids y

Itaconic acid hybrids as potential anticancer agents.

In this paper, we report the synthesis of novel hybrids 2-14 based on itaconic acid and fluoroaniline, pyridine, indole and quinoline scaffolds. Itaconic acid is a naturally occurring compound with a Michael acceptor moiety, a key structural feature in several anticancer and antiviral drugs, responsible for the covalent binding of a drug to the cysteine residue of a specific protein. Aromatic parts of the hybrids also come from the substances reported as anticancer or antiviral agents. The synthetic route employed to access the amido-ester hybrids 2-13 used monomethyl itaconate or monomethyl i

Clinical efficacy of subgingivally-delivered 0.75% boric acid gel as an adjunct to mechanotherapy in chronic periodontitis: A randomized, controlled clinical trial.

AIM: Borinic acid quinoline esters are a recently-identified class of new antibacterial and anti-inflammatory compounds known to inhibit osteoclastic bone resorption. They have proposed to have osteostimulative properties by causing osteoblast differentiation in vivo and in vitro. The purpose of this double-masked, randomized, controlled clinical trial was to evaluate the effects of the subgingival delivery of boric acid gel as an adjunct to scaling and root planing (SRP) on clinical and radiographic parameters, and compare this method with SRP plus placebo gel alone in chronic periodontitis (

Antimutagenic and Antioxidant Activities of Thai Rice Brans.

BACKGROUND: Rice bran is the outer layer of the rice grain, and contains high amounts of bioactive phytochemicals. Here, we investigated and compared chemopreventive properties of purple and white rice bran extracts. METHODS: Rice bran was extracted with dichloromethane and methanol. Chemical constituents in the extracts were analyzed by colorimetric assay and high performance liquid chromatography. The mutagenicity and antimutagenicity of the extracts were determined via the Salmonella mutation assay. The anticarcinogenic enzyme induction and antioxidant activities of the extracts were exami

Diagnosis of abdominal tuberculosis by multi-targeted (mpt64 and IS6110) loop-mediated isothermal amplification assay.

BACKGROUND AND AIM: Diagnosis of abdominal TB is an exigent task due to variable anatomical sites and non-specific clinical manifestations that closely resemble other diseases. Most of the available diagnostic modalities yield low sensitivities and need expertise to handle the specialized equipment. Hence, there is an urgent need to develop a rapid and reliable diagnostic test, so as to reduce the unnecessary morbidity. Therefore, we designed a multi-targeted loop-mediated isothermal amplification (MT-LAMP) for diagnosing abdominal TB. METHODS: We evaluated an MT-LAMP (using mpt64 and IS6110)

Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine.

Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat Plasmodium falciparum malaria in multiple Southeast Asian countries, is now increasingly failing in Cambodia, where artemisinin resistance is nearly fixed, which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of the genes encoding plasmepsins 2 and 3 is a molecular marker of PPQ resistance; however, whether these enzymes play a role in the mechanism of resistance is currently unknown. We sh

A foldamer approach to targeting membrane bound helical states of islet amyloid polypeptide.

A small molecule, protein mimetic based approach is shown to specifically inhibit lipid catalysed self-assembly of islet amyloid polypeptide (IAPP). The lipid-bound oligomerization of this peptide is implicated in cellular dysfunction of insulin secreting β-cells in type II diabetes.

Excitotoxic neuronal death and the pathogenesis of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative hereditary illness originated by the mutation of the gene encoding the huntingtin-protein (htt). Mutated htt (mhtt) is characterized by an increased number of glutamine repeats in the N-terminal end; when 40 or more glutamine residues are present, the disease is manifested. Expression of mhtt leads to the selective death of the medium spiny neurons (MSN) in the neostriatum, resulting in the appearance of generalized involuntary movements, the main phenotypic alteration of HD. The relationship between the expression of mhtt and the death of the M