Characteristic Functional Changes Research Articles

Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Establishment of a canine model of pulmonary arterial hypertension induced by dehydromonocrotaline and ultrasonographic study of right ventricular remodeling

ABSTRACT Objective Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling. Methods Twenty healthy beagle dogs (8–10 kg) were randomly divided into control group (N-dimethylformamide, n = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed. Results At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP (r = 0.74, P < .001), mRVP (r = 0.72, P < .001), PASP (r = 0.75, P < .001), mPAP (r = 0.72, P < .001) and PVR (r = 0.68, P < .001). There was a significant positive correlation between RVLS and RVHI (r = 0.74, P < .001). Conclusion The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH.

Experimental Study on the Characteristic Changes of the Immunological Microenvironment at the Maternal-Fetal Interface in IVF-ET Pregnancy

To investigate the characteristic functional changes of the decidual natural killer (NK) cells and γδ T cells, two immunocytes in the decidua, at the maternal-fetal interface in in vitro fertilization-embryo transfer (IVF-ET) pregnancy. Decidual samples were collected from 12 women of natural pregnancy (NP) and 32 women of IVF-ET pregnancy, who were enrolled in the NP group and the IVF-ET group, respectively. Then part of the decidual samples were paraffin-embedded for HE staining and immunofluorescence staining, while the rest of the samples were digested and Percoll was used for isolating decidual immunocytes (DICs) by gradient centrifugation. Flow cytometry was used to determine the cell counts of decidual NK cells and γδ T cells and the expression levels of their surface activation markers, CD69 and NKG2D in the NP and the IVF-ET groups. In addition, the expression levels of IFN-γ, TNF-α, IL-17A, and IL-10, the intracellular cytokines, and granzyme B, perforin, and granulysin, the cytolytic granules, were measured. The characteristic changes in the relevant immunological indicators were compared and analyzed. HE staining of the tissue specimens showed that the typical structure of decidua was observed, and that lymphocytes were enriched in the decidua. Immunofluorescence staining showed that the percentage of decidual NK (dNK) cells in nucleated cells of the IVF-ET group was significantly lower than that of the NP group ( P<0.05). Flow cytometry analysis of DICs showed that, compared with those of the NP group, the percentage of dNK cells of the IVF-ET group was decreased ( P<0.05) and the expression levels of IL-10 and perforin were significantly decreased in the IVF-ET group ( P<0.05). However, there was no significant difference in the decidual γδ T (dγδT) cell count between the two groups. The expression of IL-10, IL-17A, and perforin was downregulated in the IVF-ET group ( P<0.05). There was no significant difference in the expression of IFN-γ, TNF-α, granzyme B, and granulysin, the cellular function indicators ( P>0.05). The dNK cell count and the secretion of some intracellular cytokines of dNK and dγδT cells of women of IVF-ET pregnancy decreased to some degree, which suggests that certain changes may have taken place in the immunological microenvironment at the maternal-fetal interface. The specific effect of these changes on pregnancy outcomes needs further investigation.

Genetic Types of Inheritance of Retinal Pigment Abiotrophy in Patients Living in “Closed” Communities in the Republic of Buryatia

Retinal pigment abiotrophy is a hereditary disease with a primary diffuse lesion of photoreceptors and the retinal pigment epithelium, in which characteristic functional changes and a typical picture of the fundus with pigment bone bodies are noted. Retinal pigment abiotrophy is the most common disease of all dystrophies of the retina.Aim. To do a clinical genealogical analysis of the type of inheritance of pigmentary retinitis in residents of Tarbagatai region of the Republic of Buryatia.Material and methods. At the first stage of the study, a round between the residents of Tarbagatai region of the Republic of Buryatia was conducted by interviewing and questioning. At the second stage, people with suspected pigment retinitis and their blood relatives underwent a full ophthalmologic examination to confirm the diagnosis, and a thorough collection of genealogical information was carried out to determine the type of inheritance.Results. 20 patients were allocated from 12 families of 1237 interviewed people aged 15 to 76 years living in a closed community in the territory of Buryatia in the Tarbagatai region, 12 of them with a presumptive diagnosis of retinitis pigmentosa, with signs of Usher syndrome (retinitis pigmentosa + sensorineural hearing loss) – 8 people. In general, the analysis of 20 pedigrees with an established type of inheritance in 89.9 % of cases revealed an autosomal recessive type; in 10.1 % – autosomal dominant type of retinitis pigmentosa.Conclusion. A complete collection of genealogical history is the basis for the diagnosis of hereditary eye diseases.

Optimizing diagnosis in Parkinson's disease: Radionuclide imaging

Parkinson's disease (PD) and other disorders characterized by basal ganglia dysfunction are often associated with limited structural imaging changes that might assist in the clinical or research setting. Radionuclide imaging has been used to assess characteristic functional changes. Presynaptic dopaminergic dysfunction in PD can be revealed through the imaging of different steps in the process of dopamine synthesis and storage: L-aromatic amino acid decarboxylase (AADC) activity, Vesicular Monoamine Transporter type 2 (VMAT2) binding or its reuptake via the dopamine transporter (DAT). Postsynaptic dopamine dysfunction can also be studied with a variety of different tracers that primarily assess D2-like dopamine receptor availability.The function of other neurotransmitters such as norepinephrine, serotonin and acetylcholine can be imaged as well, giving important information about the underlying pathophysiologic process of PD and its complications. The imaging of metabolic activity and pathologic changes has also provided great advances in the field.Together, these techniques have allowed for a better understanding of PD, may be of aid for differentiating PD from other forms of parkinsonism and will undoubtedly be useful for the establishment of new therapeutic targets.

Alterations of striatal glutamate transmission in rotenone-treated mice: MRI/MRS in vivo studies

Animal models treated with agricultural chemicals, such as rotenone, reproduce several degenerative features of human central nervous system (CNS) diseases. Glutamate is the most abundant excitatory amino acid transmitter in the mammalian central nervous system and its transmission is implicated in a variety of brain functions including mental behavior and memory. Dysfunction of glutamate neurotransmission in the CNS has been associated with a number of human neurodegenerative diseases, either as a primary or as a secondary factor in the excitotoxic events leading to neuronal death. Since many human CNS disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by toxic agents. Candidate environmental toxins bearing any direct or indirect effects on the pathogenesis of human disease are particularly useful. The present longitudinal Magnetic Resonance Imaging (MRI) studies show, for the first time, significant variations in the properties of brain ventricles in a rotenone-treated (2 mg/kg) mouse model over a period of 4 weeks following 3 days of rotenone treatment. Histopathological analysis reveals death of stria terminalis neurons following this short period of rotenone treatment. Furthermore, in vivo voxel localized 1H MR spectroscopy also shows for the first time significant bio-energetic and metabolic changes as well as temporal alterations in the levels of glutamate in the degenerating striatal region. These studies provide novel insights on the effects of environmental toxins on glutamate and other amino acid neurotransmitters in human neurodegenerative diseases.

Neurotoxicant-induced animal models of Parkinson's disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration.

The etiologic basis of Parkinson's disease (PD), the second most common age-related neurodegenerative disorder, is unknown. Recent epidemiological and experimental studies indicate that exposure to environmental agents, including a number of agricultural chemicals, may contribute to the pathogenesis of this disorder. Animal models are important tools in experimental medical science for studying the pathogenesis and therapeutic intervention strategies of human diseases. Since many human disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by neurotoxic agents. Recently, agricultural chemicals, when administrated systemically, have been shown to reproduce specific features of PD in rodents, thus opening new routes for the development of animal models for this disorder. In addition to a brief historical overview of the toxin-induced PD models, this study provides a detailed description of exiting models in which Parkinsonism is initiated via the exposure of animals to such agricultural chemicals as rotenone, paraquat, and maneb. Suggested neurotoxicity mechanisms of these chemicals are considered, and the major lessons learned from the analysis of pesticide-induced PD models are discussed.

Neurochemical findings in the MPTP model of Parkinson's disease.

Animal models are a very important approach to study the pathogenesis and therapeutic intervention strategies of human diseases. Since many human disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by neurotoxic agents. For instance, the application of the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is able to produce striking similarities to Parkinson's disease (PD) diagnosed in humans. MPTP is thought to selectively damage dopaminergic neurons predominantly those originating in the substantia nigra pars compacta (SNc) which leads to impaired dopaminergic neurotransmission accompanied by a loss of dopaminergic nerve terminals in the striatum. MPTP-induced neurochemical, behavioral, and histopathological alterations replicate very closely the clinical symptoms of PD patients, which will be discussed in this paper and render the MPTP model currently the most favored PD model to study therapeutic intervention strategies in an easy and reliable way in preclinical studies. We and many other research groups propose that the knowledge about the neurotoxic mechanisms of MPTP such as mitochondrial dysfunction with breakdown of energy metabolism and free radical production will help us to understand the underlying mechanisms of PD, which are not fully understood yet. In particular, the novel aspects of inflammatory processes and the involvement of reactive nitrogen species in addition to reactive oxygen species seem to be important milestones for a better understanding of the neurodegenerative effects of MPTP. In this review we focus on the MPTP mouse model which is easy practicable and widely used in neuroscience research and draw comparisons to the human pathology in PD.

Pulmonary function in children with sarcoidosis.

To document pulmonary function abnormalities in children with sarcoidosis, we reviewed the records of all children with this disease at the North Carolina Memorial Hospital. Spirometry was performed by 34 of 60 children at initial presentation and was repeated by 16 at least 1 yr after presentation (mean, 3.9 yr). Those with and without pulmonary function data available were similar in age, sex, race, and clinical manifestations at presentation. Results indicate that at presentation, 50% of children had the characteristic functional changes of restrictive lung disease (mean % predicted FVC, 79.8 +/- 16.0). Fifteen percent had a FVC of 70 to 80% predicted, 32% had a FVC of 50 to 70% predicted, and 3% had a FVC less than 50% predicted. The TLC and FRC supported the diagnosis of restrictive lung disease. There were 15% who had obstructive changes. Children with auscultatory abnormalities and parenchymal changes on chest radiograph had more severe decrements in pulmonary function; however, specific symptoms did not predict decrements in pulmonary function. There was significant improvement in lung function at the last pulmonary function test performed (mean % predicted FVC, 97.1 +/- 18.8).

Airway function in stage I and stage II pulmonary sarcoidosis.

Airway function was studied in 39 patients with stage I sarcoidosis and in 20 patients with stage II sarcoidosis. All of our patients were nonsmokers. Characteristic functional changes of restrictive lung disease was observed in 4 patients with stage II sarcoidosis. Specific airway conductance and % FEV1 were abnormal in 3 patients with stage II sarcoidosis. Abnormal small airway function was demonstrated in several patients with stage I and stage II sarcoidosis, always by multiple tests. Frequency dependence of dynamic compliance was demonstrated in 40% of stage I and 50% of stage II sarcoidosis. Maximal flow (Vmax50, Vmax25) was decreased respectively in 36 and 30% of patients of stage I sarcoidosis and in 56 and 62% of patients with stage II sarcoidosis. The ratio of closing volume to vital capacity was increased above corrected predictions in 30% of stage I and 44% of stage II sarcoidosis. delta Vmax25 decreased and Visov/VC (%) increased in more than 50% of patients. Upstream airway resistance was abnormally increased in 50% of patients with stage I and in 73% with stage II sarcoidosis. These results suggest that small airway dysfunction is common in early sarcoidosis without restrictive defect.

Airway function in sarcoidosis

Airway function was studied in 18 patients with sarcoidosis, aged 18 to 49 years. Eleven of the patients were smokers. All patients had the characteristic functional changes of restrictive lung disease: decreased lung volumes and single breath diffusing capacity, and increased static transpulmonary pressures. Abnormal airway function was demonstrated in every patient by at least one test, and nearly always by multiple tests. Specific airway conductance was abnormally low in two patients. The ratio of the 1 second forced expiratory volume to the forced vital capacity was decreased in six patients. Frequency dependence of dynamic compliance was demonstrated in eight patients. The ratio of closing volume to vital capacity was increased above age-corrected predictions in all but two patients. Upstream airway resistance was abnormally increased in 16 of the patients. These results suggest that airway dysfunction is not uncommon in sarcoidosis.