differential function
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2021 ◽  
Vol 12 (1) ◽  
pp. 86
Pilar Marcos ◽  
Rafael Coveñas

To know the processes involved in feeding, the dysregulation of hypothalamic neuropeptides promoting anorexigenic/orexigenic mechanisms must be investigated. Many neuropeptides are involved in this behavior and in overweight/obesity. Current pharmacological strategies for the treatment of obesity are unfortunately not very effective and, hence, new therapeutic strategies must be investigated and developed. Due to the crucial role played by orexins in feeding behavior, the aim of this review is to update the involvement of the orexinergic system in this behavior. The studies performed in experimental animal models and humans and the relationships between the orexinergic system and other substances are mentioned and discussed. Promising research lines on the orexinergic system are highlighted (signaling pathways, heterogeneity of the hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences). Each of the orexin 1 and 2 receptors plays a unique role in energy metabolism, exerting a differential function in obesity. Additional preclinical/clinical studies must be carried out to demonstrate the beneficial effects mediated by orexin receptor antagonists. Because therapies applied are in general ineffective when they are directed against a single target, the best option for successful anti-obesity treatments is the development of combination therapies as well as the development of new and more specific orexin receptor antagonists.

2021 ◽  
pp. 1-6
Eda Tokat ◽  
Serhat Gurocak ◽  
Ozgur Akdemir ◽  
Ipek Isik Gonul ◽  
Mustafa Ozgur Tan

<b><i>Introduction:</i></b> In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). <b><i>Methods:</i></b> The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. <b><i>Results:</i></b> The mean age of the patients was 8.52 ± 8.86 (0–35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0–5 cells (low) in 19 (46.3%) patients and &#x3e;5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (<i>p</i> = 0.001-low, <i>p</i> = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (<i>p</i> = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (<i>p</i> = 0.02). Postoperative T1/2 decreased in both low (<i>p</i> = 0.000) and moderate-high (<i>p</i> = 0.001) Cajal groups, but no difference was found between them (<i>p</i> = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (<i>p</i> = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (<i>p</i> = 0.51). <b><i>Discussion/Conclusion:</i></b> ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 411
Joanna Bartosińska ◽  
Joanna Purkot ◽  
Agnieszka Karczmarczyk ◽  
Michał Chojnacki ◽  
Joanna Zaleska ◽  

Psoriasis (Ps), an autoimmune disease, and multiple myeloma (MM), a blood neoplasm, are characterized by immune dysregulation resulting from the imbalance between the effector and regulatory cells, including B regulatory (Breg) lymphocytes. Peripheral blood samples from 80 Ps patients, 17 relapsed/refractory MM patients before and after daratumumab (anti-CD38 monoclonal antibody) treatment, 23 healthy volunteers (HVs), and bone marrow samples from 59 MM patients were used in the study. Bregs were determined by flow cytometry using CD19, CD24, and CD38. Intracellular production of interleukin-10 (IL-10) was assessed by flow cytometry after CD40L, LPS, and CpG stimulation. IL-10 serum or plasma concentrations were tested using ELISA method. The percentage of CD19+CD24hiCD38hi Bregs was not different whereas the production of IL-10 in Bregs was significantly higher in Ps patients in comparison with HVs. The percentage of CD19+CD24hiCD38hi Bregs in MM patients was significantly higher than in HVs (p < 0.0001). The percentage of CD19+CD24hiCD38hi Bregs was significantly higher in MM patients with the ISS stage I (p = 0.0233) while IL-10 production in Bregs was significantly higher in ISS stage III (p = 0.0165). IL-10 serum or plasma concentration was significantly higher in Ps and MM patients when compared to HVs (p < 0.0001). Following the treatment with daratumumab the percentages of CD19+CD24hiCD38hi Bregs significantly decreased (p < 0.0003). Here, in the two opposite immune conditions, despite the differences in percentages of Bregs in Ps and MM we have identified some similarities in the IL-10 producing Bregs. Effective treatment of daratumumab besides the anti-myeloma effect was accompanied by the eradication of Bregs.

2021 ◽  
Vol 15 (2) ◽  
pp. 25-34
Petro Shcherbakov ◽  
Svitlana Tymchenko ◽  
Marat Bitimbayev ◽  
Nurzhigit Sarybayev ◽  
Serik Moldabayev

Purpose is to determine a function of the reduced expenditures connected with drilling-and-blasting operations, loading and hauling operations, and rock fragmentation depending upon the cost of machine-shift of the applied facility, its operation modes, hardness of rock being blasted, cost of the used explosive, and rock fragmentation quality based upon the developed optimization mathematical model. Methods. Method of statistical evaluation of natural blockiness structure of the rock as well as quality of its fragmentation by means of explosive energy has been applied. Statistical studies have been carried out concerning the basic indices of rock fragmentation depending upon its largeness and block hardness. Purposely-designed experimental equipment has been applied for sampling analysis of the rock fracturing in the process of its drilling by means of rotary drilling rig. The abovementioned supported representativeness of the sampling. Findings. Statistical distributions of the rock blockiness structure in terms of each bar length involving its place within the drilling assembly as well as in terms of the well depth have been compiled. Visual comparison of experimental data and theoretical data has helped determine that the statistical distributions of natural blockiness structure of the rock have the closest correlation with gamma distribution which differential function has two positive parameters. Statistical dependence has been defined between drilling-and-blasting results and the total expenditures connected with hard rock mining. Originality. A concept of oversize crushing coefficient has been introduced; its statistical dependence upon the mined rock hardness and specific consumption of the applied explosive has been derived. An alternative has been proposed concerning changes in parameters of the differential function of the assumed gamma distribution relative to the predicted granulometric composition of rock mass. Practical implications. Economic and mathematical model has been developed involving a target function of the total expenditures connected with the listed operations as well as a set of constraints avoiding incorrect decisions. The optimization method makes it possible to control drilling-and-blasting parameters at each stage of hard rock mining.

2020 ◽  
Vol 147 (11) ◽  
pp. 3139-3151
Yong Zhang ◽  
Aimin Xie ◽  
Fei Quan ◽  
Xiaobo Hou ◽  
Jianlong Liao ◽  

2020 ◽  
Vol 1003 ◽  
pp. 134-143
Yang Ming ◽  
Lin Mian

This article proposes the differential BJH equation based on the principles of multilayer adsorption and capillary condensation, which was simplified by theoretical investigation and experiments. This work indicates that the differential function of isotherm and the differential function of pore size to relative pressure determine the pore size distribution of porous media. The differential BJH model can be used to explain the source of the false peak in pore size distribution and to calculate the pore size distribution of different shapes of pores in a porous media with a porous structure. It has an excellent application prospect in the characterization of complex pore structure represented by shale.

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