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Metabolic profiling of complex biological matrices based on liquid chromatography-mass spectrometry (LC-MS) allows detecting a wide range of metabolites with distinct concentrations and physicochemical properties. Given the complexity of samples and the necessity of a comprehensive approach in untargeted metabolomics, quality control strategies are mandatory to obtain high-quality data. The LC-MS performance must be monitored and evaluated to guarantee data reliability. In this study, a test mixture (TM) was developed, systematically evaluated, and applied to untargeted metabolomics of urine samples from individuals suspected of inborn errors of metabolism. The TM was composed of fifteen analytes that eluted across the entire gradient in reversed-phase columns and ionized in positive/negative electrospray modes. It helped set the LC-MS conditions for urine analysis, from sample reconstitution solvent to selecting the MS ion source parameters. The TM quickly indicated column stationary phase degradation during the batch analysis when employed to monitor and evaluate the LC-MS system in an untargeted metabolomic analysis. Thus, in addition to pooled QC samples, a TM can be employed in untargeted metabolomics to rapidly assess the system performance avoiding unnecessary efforts for further data treatment and multivariate analysis of poor-quality data

The comprehended knowledge of the metabolic profile of the fecal matter has been recognized as an important point for understanding metabolic changes in the human systemic metabolism and it can provide precious information about host-gut microbiota interactions. However, few analytical strategies have been addressed for a broad analysis of metabolites with different chemical properties to better understand the chemical space of fecal samples. Here we report a systematic pipeline to achieve comprehensive coverage of the fecal metabolome, from high polar to nonpolar metabolites, using dog fecal samples as a proof-of-concept. This pipeline comprises a monophasic (ACN/H2O) and a biphasic extraction (methyl tert-butyl ether (MTBE)/MeOH/H2O) of the sample, followed by three liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) methods using HILIC-amide, RP-C18 and CSH-C18 columns, and a switch polarity acquisition mode in the electrospray ion source. This approach allowed the annotation of 376 metabolites from 70 different chemical classes. The chemical space analysis by molecular networking and the pathway analysis revealed the complexity of the fecal sample and the importance of combined methods to better understand biochemical pathways. This pipeline can be used as a valuable tool to comprehend the relationship between host-gut microbiota metabolites and the influence of diet, medication, or environmental changes.

This paper discusses metrologically the best practice regarding the calibration curves applied to H2S mass fractions determination in natural gas by gas chromatography with sulfur chemiluminescence...

We evaluated ants as bioindicators of environmental impacts caused by arsenic residuals in the soil. We tested the hypotheses that the presence of arsenic in the soil affects: (1) estimates of resources and habitat condition for arboreal and epigaeic ants; (2) species richness of arboreal and epigaeic ants and (3) arboreal and epigaeic ant species composition. Ants were sampled at an inactivated raticide factory in Nova Lima, Minas Gerais, Brasil, which used arsenic as one of its main byproducts. The following environmental variables were measured: bioavailable arsenic concentration in the soil, the number and density of tree species, plant cover and leaf litter depth. The species richness of arboreal ants decreased with increased bioavailable arsenic concentration whilst epigaeic ants increased with arsenic. Arboreal ants were positively related to the number of tree species, which in turn were negatively affected by arsenic. We verified which ants are good bioindicators of arsenic. Independent verification of the influence of arsenic on background environmental variables was fundamental in defining responses of ant communities, as well as in identifying the most effective pathways for the recovery of biological communities in degraded areas.

UV and PMR spectra of 1-methyl-4-phenylpyrazoles indicate the existence of conjugation between the phenyl and pyrazole rings. The UV spectra are found to be solvent dependent. This solvent effect can be explained, if considerable resonance interaction is assumed.

Substituents with electron withdrawing capacities are found to induce a paramagnetic displacement of the chemical shifts of protons and methyl groups in the remaining positions of the pyrazole ring. For the 4-position this effect is considered to be due primarily to resonance interaction of substituent and pyrazole ring.

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

Treatment of 4-substituted 3,5-dimethyl-1-nitro-1H-pyrazoles 1 and 10a-c with secondary amines in acetonitrile, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affords the novel dialkyl-aminomethyl-1H-pyrazoles 5, 6, 7, 8, 11a-c, 12a-c and 13a-c in good to excellent yields. In this way one of the, in general, inert methyl groups of 3,5-dimethyl-4-substituted-1H-pyrazoles is functionalized creating a new synthetic route to azoles containing a coordinating substituent.

Addition of 3 equivalents of DBU or DBN to a solution of 4-halo-3,5-dimethyl-1-nitro-1H-pyrazole ( 5a-c ) in acetonitrile affords the unexpected products 6a-c and 7a-c in fair to good yields. A reaction mechanism is proposed involving an elimination of HNO 2 giving a diazafulvene intermediate 8 followed by the addition of a second molecule of DBU or DBN to 8 .

La copulation azoique conduit aux piperidinoazo-2-, pyrrolidinoazo-2- et morpholinoazo-2 N-oxy benzenediazoates de piperidinium, pyrrolidinium ou morpholinium

Immunohistochemical techniques were used to determine the intermediate filament content of normal arachnoidal cells, meningiomas (including the so-called hemangiopericytoma of the meninges), soft tissue hemangiopericytoma, and the normal pericyte. Arachnoid granulations and all types of meningioma stained similarly: positive for vimentin and variably positive for keratin. Soft tissue hemangiopericytomas and normal pericytes were negative for both vimentin and keratin. This suggests that the "hemangiopericytoma" of the meninges is a variant of meningioma and not of pericytic origin.

Selon les conditions de reaction des tribromo-3,4,5- et dibromo-3,5 nitro-1 pyrazoles, on obtient divers composes parmi lesquels des nitro-4- ou -5 1H-pyrazoles. Proposition de mecanisme de reaction

An unusual neuropsychiatric disorder inherited in autosomal dominant fashion occurred in three successive generations of a family. Symptoms commenced late in the fifth decade in six affected patients and led to death in four to six years. The earliest and most prominent symptom was mental depression not responsive to antidepressant drugs or electroconvulsive therapy. This was accompanied by exhaustion, sleep disturbances, and marked weight loss. Later in the disease, symptoms of parkinsonism appeared, and respiratory failure occurred terminally. The most recently affected family member was investigated biochemically late in his illness. Concentrations of taurine were greatly diminished in plasma and cerebrospinal fluid, and at autopsy, all regions of brain examined had a markedly reduced taurine content. Since taurine is a putative inhibitory synaptic transmitter, deficiency of brain taurine may possibly have caused the psychiatric and neurological manifestations of this disorder.

Three infants in one sibship are described, each of whom died during the third month of life after illnesses characterized by irritability and progressive somnolence, and terminally by a tendency to bleed and hypoglycemia. Each infant had a very peculiar odor for several weeks before death. Autopsy disclosed almost identical pathological changes in each infant, consisting of hepatic cirrhosis, renal tubular dilatation, and pancreatic islet hypertrophy. Biochemical investigation of the third infant demonstrated, besides a generalized aminoaciduria, a very marked elevation of methionine in serum, and a disproportionately high excretion of this amino acid in urine. Normal brain cystathionine concentration, and absence of excessive amounts of homocystine and cystathionine from urine, indicated that the major known pathway of methionine degradation was intact. α-Keto-γ-methiolbutyric acid was found in the infant's urine and may have been responsible for the patient's odor. It is suggested that an alternative pathway of methionine breakdown, in addition to that leading through cystathionine, exists in man, and that an enzymatic block, possibly in the oxidative decarboxylation of the alpha keto acid of methionine, might conceivably have accounted for the disease found in these infants.

UV and PMR spectral data and CO frequencies of some methylpyrazoles containing in the 3-, 4- or 5-position, a formyl-, acetyl- or ethoxycarbonyl group are reported. These data confirm earlier conclusions that, in particular, the 4-pyrazolyl group acts as an electron releasing group. The syntheses of a number of formyl-, acetyl- and ethoxycarbonyl pyrazoles are described. In addition, some 4-dicyanovinyl- and 4-tricyanovinylpyrazoles were investigated.

In contrast to nitration with nitric acid in sulfuric acid giving 4-(o,p-dinitrophenyl)-l-methylpyrazole 2, both the phenyl and the pyrazole ring are substituted on nitration with acetyl nitrate. With the latter method also a predominant ortho substitution in the phenyl ring is observed. It is concluded, that the pyrazole ring is quite susceptible to nitration at positions other than the, hitherto favoured, 4-position.

The synthesis of al six isomers of 1,1′-dimethylbipyrazolyl is reported. Their structure assignments were based on mnr data. Nmr spectra were determined in widely different solvents and structure assignments were based on these data, particularly on the found solvent effect. Uv spectral data are also reported.

The 13C NMR spectra of 1,5- and 2,x-dinitroindazoles “x=4-7” and 3-bromo-1,x-dinitroindazoles are recorded and discussed. The data on he 2,x-dinitroindazoles confirm our previous structurea assignment based on 1H NMR spectroscopy. The 13C NMR spectra established that in the novel 3-bromo-1,x-dinitroindazoles the N-nitro group is attached at N-1.

The synthesis of 2-nitro-4,5,6,7-tetrachloro-2H-benzotriazole 1 and of 2-nitro-2H-phenanthro[9,10-d]-triazole 2 and their transfer of the nitro group to give 1-nitropyrrolidine 4a and 1-nitromorpholine 4b in high yields when reacted with pyrrolidine or morpholine are reported. The reaction of 1 also gives the pyrrolidinium and morpholinium salts 5a-b of 1.

✓ The case is reported of a patient in whom a cervical lymph node metastasis decreased in size while the primary intracranial glioblastoma continued to grow during chemotherapy with CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea). This is the first such case reported in humans. Possible explanations for this phenomenon are discussed.