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Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.

Rationale: Sample preparation is one of the most crucial steps for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Scientists beginning their study with this technique may be overwhelmed by the variety of matrices, solvents, and concentrations; the methods of their applications; and the lack of widely available knowledge of the effect of these parameters on the results. Here we present in depth the aspects of matrix deposition, which will be helpful for the scientific community., Methods: In this study, we tested several MALDI matrices, such as 2,5-dihydroxybenzoic acid (DHB), norharmane, N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC), and 9-aminoacridine (9AA), using the SunCollect system: wet-interface matrix deposition in the context of lipid analysis. We optimized the number of matrix layers and nozzle settings in terms of spectral intensity and the overall quality of the obtained ion maps., Results: Our research presents the effect of the number of matrix layers and nozzle settings on the results and allows for choosing the optimal parameters for the analyses. In positive ionization mode, DHB matrix could be chosen first. In the negative ionization mode, 1,5-diaminonaphthalene matrix produces a higher peak intensity in a lower mass range and seems to provide more information than 9AA. We recommend NEDC for particular processes such as glucose analysis. Compared to the remaining matrices, norharmane shows significant changes in the obtained ion maps., Conclusions: Such a large amount of data allow us to observe an interesting conclusion: the obtained ion image for a particular ion could differ dramatically with a change in the matrix, the solvent composition, or even the number of matrix layers. This must be considered when interpreting the result, impelling us to compare the results obtained with different matrices with caution., (© 2023 John Wiley & Sons Ltd.)

The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain-gut-microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites' levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.

(1) Background: Recent data indicate that receptors for GLP-1 peptide are involved in the activity of the mesolimbic system. Thus, the purpose of the present study was to examine the effect of the selective dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on morphine dependence in mice. (2) Methods: Morphine dependence in mice was obtained by administration of increasing doses of morphine for eight consecutive days, twice a day. On the 9th day of the experiment, the naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (jumping) were assessed. Moreover, behavioral effects of short-term (60 h after morphine discontinuation) and long-term (14 days after morphine discontinuation) morphine withdrawal were observed. In terms of behavioral effects, the depressive effect in the forced swim test and anxiety in the elevated plus maze test were investigated. Locomotor activity of mice was also studied. (3) Results: The administration of linagliptin (10 and 20 mg/kg, ip) for 8 consecutive days before morphine injections significantly diminished the number of naloxone-induced morphine withdrawal signs (jumping) in mice. In addition, the cessation of morphine administration induced depressive behavior in mice which were observed during short- and long-term morphine withdrawal. Linagliptin administered during morphine withdrawal significantly reduced the depressive behavior in studied mice. Furthermore, the short-term morphine withdrawal evoked anxiety which also was reduced by linagliptin in mice. (4) Conclusions: The present study reveals that GLP-1 receptors are involved in morphine dependence. What is more, linagliptin might be a valuable drug in attenuating the physical symptoms of morphine dependence. It might be also a useful drug in reducing emotional disturbances which may develop during the morphine withdrawal period.

As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM.

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B 1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, - 3.2, - 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at - 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B 1  = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure., (© 2021. The Author(s).)

Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone., (© 2021. The Author(s).)

The aim of this paper is to compare the results of kinematic viscosity of lubricating oils measurements at 40 °C, obtained with three different rapid evaluation devices, and the standardized method using an Ubbelohde Capillary viscometer. The following instruments were selected to measure: a mid-FTIR spectrophotometer, a microchannel viscometer, and a Stabinger viscometer. The study material comprised 42 fresh engine oils, all of which are commercially available. The main data analysis tools used in the study were multiple regression, Mahala Nobis distance, post-hoc analysis, and the Wilcoxon signed-rank test with the Bonferroni correction. Consistent outcomes were obtained for the Stabinger viscometer only, whereas the microchannel viscometer and the mid-FTIR spectrophotometer were not as precise as the reference method. It was also found that the results obtained with the use of the mid-FTIR spectrophotometer were burdened with a very large measurement error. Therefore, a very careful approach is suggested when choosing these instruments. The study fills an important gap in empirical research in the context of the reliability of measurement results obtained using various research techniques.

Major depressive disorder is a stress-related disease associated with brain metabolic dysregulation in the glutamine-glutamate/γ-aminobutyric acid (Gln-Glu/GABA) cycle. Recent studies have demonstrated that microbiome-gut-brain interactions have the potential to influence mental health. The hypothesis of this study was that Lactobacillus rhamnosus JB-1 (LR-JB1™) dietary supplementation has a positive impact on neuro-metabolism which can be quantified in vivo using magnetic resonance spectroscopy (MRS). A rat model of depressive-like disorder, chronic unpredictable mild stress (CUMS), was used. Baseline comparisons of MRS and behavior were obtained in a control group and in a stressed group subjected to CUMS. Of the 22 metabolites measured using MRS, stressed rats had significantly lower concentrations of GABA, glutamate, glutamine + glutathione, glutamate + glutamine, total creatine, and total N-acetylaspartate (tNAA). Stressed rats were then separated into 2 groups and supplemented with either LR-JB1™ or placebo and re-evaluated after 4 weeks of continued CUMS. The LR-JB1™ microbiotic diet restored these metabolites to levels previously observed in controls, while the placebo diet resulted in further significant decrease of glutamate, total choline, and tNAA. LR-JB1™ treated animals also exhibited calmer and more relaxed behavior, as compared with placebo treated animals. In summary, significant cerebral biochemical downregulation of major brain metabolites following prolonged stress were measured in vivo using MRS, and these decreases were reversed using a microbiotic dietary supplement of LR-JB1™, even in the presence of continued stress, which also resulted in a reduction of stress-induced behavior in a rat model of depressive-like disorder., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this paper, we focus on detection of speed changes from audio data, representing recordings of cars passing a microphone placed near the road. The goal of this work is to observe the behavior of drivers near control points, in order to check whether their driving is safe both when approaching the speed camera and after passing it. The audio data were recorded in controlled conditions, and they are publicly available for downloading. They represent one of three classes: car accelerating, decelerating, or maintaining constant speed. We used SVM, random forests, and artificial neural networks as classifiers, as well as the time series based approach. We also tested several approaches to audio data representation, namely: average values of basic audio features within the analyzed time segment, parametric description of the time evolution of these features, and parametric description of curves (lines) in the spectrogram. Additionally, the combinations of these representations were used in classification experiments. As a final step, we constructed an ensemble classifier, consisting of the best models. The proposed solution achieved an accuracy of almost 95%, without mistaking acceleration with deceleration, and very rare mistakes between stable speed and speed changes. The outcomes of this work can become a basis for campaigns aiming at improving traffic safety.

A novel elastic hydroxyapatite-based composite of high surgical handiness has been developed. Its potential application in orthopedics as a filler of bone defects has been studied. The biomaterial was composed of carbonated hydroxyapatite (CHAP) granules and polysaccharide polymer (β-1,3-glucan). Cylinders of 4mm in diameter and 6mm in length were implanted into bone cavities created in the proximal metaphysis of tibiae of 24 New Zealand white rabbits. 18 sham-operated animals were used as controls. After 1, 3 or 6 months, the rabbits were euthanized, the bones were harvested and subjected to analysis. Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. Peripheral quantitative computed tomography (pQCT) indicated the stimulating effect of the biomaterial on bone formation and mineralization. Densitometry (DXA) analysis suggested that biomineralization of bones was preceded by bioresorption and gradual disappearance of porous ceramic granules. The findings suggest that the CHAP-glucan composite material enables regeneration of bone tissue and could serve as a bone defect filler., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The authors present the case of hepatoblastoma in a young man. This type of cancer occurs rarely and it is usually diagnosed in children. The diagnosis was based on ultrasonography and computer tomography and first of all on the histopathological and immunohistochemical examination of liver biopsy. The type of cancer was epithelial and fetal. The treatment was based on chemotherapy and liver transplantation in June 2004 and then constant immunosuppression. The patient recovered with no new evidence of the disease.

The authors present the technique and the obtained results of surgical treatment of vascular malformations in the upper part of the basilar artery in 14 patients using a trans-sylvian microsurgical approach. The techniques of subfrontal and subtemporal approaches are compared.

A 47-year-old man is reported who had an extensive arteriovenous angioma of the spinal cord confirmed during operation. The patient had an atypical symptom complex, with clinically evident deep flaccid paresis of lower extremities without pyramidal signs, sensory disturbances and sphincter disturbances. The anomaly causing a steal mechanism led to ischaemia of the anterior horns of the cord.

An index of intracranial pressure instability is calculated as a new way to evaluate the capacity of intracranial voluminal compensation in patients suffering from cranio-cerebral trauma. The value of the index is determined by mutual relations of intracranial pressure standard deviations measured during 3-minute periods before and after intracranial administration of 2 ml of 0.9% NaCl. Normal physiological range of the index was evaluated in controls without intracranial pathology.

The authors present a case of intaracranial chondrome originating from the pia mater and discuss the development of intracranial chondromas and role of cranial trauma in it.

Intracranial pressure changes in dogs after intra-arterial administration of contrast media and saline in different amounts at various flow rates were studied by the authors, using continuous epidural pressure recording. In two animals the venous pressure was measured as well. Contrast media and saline alike were found to produce similar intracranial pressure increases when given intravenously though a greater rise with longer-lasting fall and successive rise of the pressure was observed when the former were used. The increase of the amount of the medium or saline had no significant effect on the value of ultracranial pressure.

Continuous measurements of intracranial, pressure were conducted by the extradural method in 40 patients with various types of skull trauma. A correlation was demonstrated between the value of this pressure and the clinical condition of the patient only with high values of the pressure, in which nearly always wave-like pressure changes were observed. The occurrence of wave-like changes was a more reliable sign of threatening cranial hypertension than the value of intracranial pressure. Continuous measurement of pressure during intravenous administration of glycerol demonstrated that a significant fall of pressure preceded the regression of clinical signs of intracranial hypertension.

The authors describe a case of osteoma of the paranasal sinuses growing into the anterior cranial fossa with liquorrhoea and aerocele treated successfully surgically from an osteoplastic transsinusal approach.

Fractures of the cranial basis in the anterior cranial fossa accounted in a ten-year period in the material of the authors for 2.6% of cranial traumas and 24.6% of cranial basis fractures. In the observed cases rhinorrhoea was present in only 16% of cases. Purulent meningitis as a complication was observed in only 1.8% of cases and only late after the trauma. In view of the low frequency of inflammatory complications evidencing a considerable tendency for spontaneous healing of fistulas the authors suggest restriction of indications to surgical treatment in early period after trauma to cases with visible wide fissure in the fractures bone, displacement of fractured fragments and their position at different levels.

On the ground of the clinical status and indicators of intracranial pressure instability and cerebral arterial reactivity the authors evaluated the efficiency of intracranial volume compensatory mechanisms in 21 patients before and after operations for epidural and subdural haematomas and spontaneous intracerebral haematomas. The epidural haematomas in a greater degree but less permanently exhausted the efficiency of the compensatory mechanisms than subdural haematomas and after their removal these mechanisms regained easier their efficiency than after removal of subdural haematomas. In cases of spontaneous intracerebral haematomas the efficiency of the compensatory mechanisms is only slightly decreased.

The authors report the clinical course of a case of carcinomatosis of the cerebrospinal meninges with frequent sudden rises of intracranial pressure and with lethal outcome. The primary tumour was a mucinous carcinoma of the ovary. In treatment Pudenz valve was used successfully for connecting the subarachnoid space of the spinal cord with the peritoneal cavity. This shunting of the cerebrospinal fluid caused no dissemination of the neoplasm within the peritoneal cavity.

The effects were analysed of various techniques of classical exclusion of aneurysms in the anterior cerebral artery system on the late therapeutic result and on the development of ischaemic lesions in the area of approach to the aneurysm. The approaches used were: interhemispheric, fronto-temporal and fronto-temporo-sphenoidal, and the aneurysms were excluded with a ligature or metal clip. The best method of approach was chosen after analysis of late results of neurological, psychological and CT studies. It was demonstrated that pressure of a spatula during the operation may produce permanent ischaemic changes at the site of the pressure which may lead to persistence of psychic disturbances late after the operation. It was shown also that the most favourable classic technique of operation in cases of aneurysms in this portion is the fronto-temporo-sphenoidal approach with use of a metal clip.