Guanxinning tablet alleviates carotid atherosclerotic plaque injury in rats / 基础医学与临床

Objective To investigate the effect and its mechanism of Guanxinning tablet on carotid atherosclerotic plaque in a rat model.Methods The rats were randomly divided into control group,model group(to construct carot-id atherosclerosis plaque model),Guanxinning groups with low,medium and high dose of Guanxinning tablet(150,300 and 600 mg/kg),atorvastatin group(2 mg/kg),lithiumchloridemonohydrate(LiCl)(Wnt/β-catenin pathway activator)group(15 mg/kg),and Guanxinning plus LiCl group(600 mg/kg Guanxinning tablets+15 mg/kg LiCl),with 12 rats in each group.The intervention began at the third week and was administered once a day for 8 weeks.Olympus Au2700 automatic biochemical analyzer was used to detect the level of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL)and high-density lipoprotein(HDL)in rat serum;ELISA was applied to detect the level of monocyte chemotactic protein(MCP-1)and hyper-sensitive C-reactive protein(hs-CRP)in rat se-rum;the level of oxidized low density lipoprotein(ox-LDL)and malondialdehyde(MDA)in rat serum were detected by spectrophotometry;HE staining was applied to find pathological changes in the common carotid artery of rats;Western blot was applied to detect the expression of Wnt3a,matrix metalloproteinase-9(MMP-9)and β-catenin in rat common carotid artery.Results Compared with the control group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,protein expression of MDA,MMP-9,Wnt3a,β-catenin and total plaque area/total arterial area ratio in-creased,the HDL level decreased in model group(P＜0.05);compared with the model group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,MDA,expression of MMP-9,Wnt3a,β-catenin protein and total plaque area/total arterial area ratio in the low,medium,and high dose groups of Guanxinning tablets decreased,the HDL level in-creased.The effect of Guanxinning tablets was dose-dependent,and the change trend of corresponding indicators in the LiCl group was opposite to the above(P＜0.05);compared with the high dose group of Guanxinning tablets,the TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,MDA levels,MMP-9,Wnt3a,β-catenin protein expression,and total plaque area/total arterial area ratio in the high dose+LiCl group of Guanxinning tablets increased,the HDL level de-creased(P＜0.05).Conclusions Guanxinning tablet can inhibit the formation of atherosclerotic plaque in rats and the mechanismis potentially related to the regulation of Wnt/β-catenin pathway.

Effects of static traction on the nucleus pulposus and annulus fibrosus of the rat intervertebral disc / 中国组织工程研究

BACKGROUND:Traction is clinically used for the early treatment of intervertebral disc degeneration,but its effect on the normal intervertebral disc remains unknown.Whether it directly causes intervertebral disc degeneration or has a positive effect is the key point of this study. OBJECTIVE:To design a static traction model and observe the effect of static traction on the nucleus pulposus and annulus fibrosus of the intervertebral disc METHODS:Twenty Sprague-Dawley rats,3 months of age,were included in the study.The intervertebral disc spaces between 7/8,8/9 and 9/10 were stretched by 1 mm,and the intervertebral disc spaces between 6/7 and 10/11 were used as control.Five rats were randomly selected at 2,4,6,and 8 weeks of traction to perform MRI T2-weighted scans of the caudal vertebra,tissue section staining,and RT-PCR gene assays for anabolic metabolism to observe the effects of static traction on the nucleus pulposus and annulus fibrosus of the intervertebral disc. RESULTS AND CONCLUSION:After short-term static traction of the rat caudal vertebra,the T2-weighted image signal in the nucleus pulposus region was enhanced.During the traction period,nucleus pulposus cells grew well,the intercellular matrix was abundant,and the annulus fibrosus arranged regularly.The RT-PCR results showed that after traction,the mRNA expression of proteoglycan increased,the expression of matrix metalloproteinase-3 decreased,the expression of type Ⅰ and Ⅱ collagen decreased,and the expression of matrix metalloproteinase-13 increased and tissue inhibitor of matrix metalloproteinase 1 increased.These gene results also indicated that traction made proteoglycan more inclined to an anabolic state,and type Ⅰ and Ⅱ collagen more inclined to a catabolic state.To conclude,static traction promotes proteoglycan anabolism making the nucleus pulposus moist.

Peripapillary Perfusion Analysis Using Optical Coherence Tomography Angiography in Patients with Normal Tension Glaucoma

Purpose@#This study aimed to assess the difference in the vascular parameters of perfusion in the optic nerve head in normal tension glaucoma (NTG) across disease stages using optical coherence tomography angiography and its correlation with peripapillary retinal nerve fiber layer (RNFL) thickness. @*Methods@#In this retrospective study, 83 eyes with varying stages of NTG (25 mild, 31 moderate, and 27 severe) and 90 healthy eyes were enrolled. The perfusion density (PD) and flux index (FI) of the optic nerve head divided into four sectors were determined. We compared the vascular, structural, and functional parameters between normal and glaucomatous eyes and performed a subgroup analysis among the NTG stages. Pearson correlation coefficient was used to assess the topographic correlation between vascular parameters and RNFL thickness. @*Results@#PD and FI were significantly decreased in the NTG group. Subgroup analysis revealed a significant decrease in vascular parameters in most regions in the NTG group, except for the nasal PD and temporal FI. Post hoc analysis showed a significant decrease in PD in the inferior region across all severity levels (mild vs. moderate, p = 0.012; moderate vs. severe, p = 0.012; mild vs. severe, p < 0.001). PD and FI were strongly correlated with RNFL thickness in all quadrants (all p < 0.001), with the strongest correlation observed in the inferior region. @*Conclusions@#Vascular parameters were significantly decreased in glaucomatous eyes, and the degree of decrease in vascular parameters was proportional to glaucoma severity. Peripapillary perfusion analysis using optical coherence tomography angiography may complement other measurements used for glaucoma diagnosis.

Diagnostic Roots Radiofrequency Sensory Stimulation Looking for Symptomatic Injured Roots in Multiple Lumbar Stenosis / 대한신경손상학회지

Objective@#We present how to perform radiofrequency sensory stimulation (RFSS) and whether RFSS could be helpful in identifying symptomatic injured roots in multilevel lumbar stenosis. @*Methods@#Consecutive patients who underwent RFSS from 2010 to 2012 were enrolled. To identify pathologic lesions, RFSS was performed for suspicious roots, as determined using lumbar magnetic resonance imaging (MRI). The RFSS procedure resembled transforaminal root block. During RFSS of the suspicious root, patients could indicate whether stimulation induced their usual pain and/or sensory changes and could indicate whether the same leg area was affected. The number of possible symptomatic roots on MRI was evaluated before and after RFSS. Based on the RFSS results, we confirmed the presence of symptomatic nerve root(s) and performed surgical decompression. Surgical results, such as numeric rating scale (NRS) scores for low back pain (LBP) and leg pain (LP), and Oswestry disability index (ODI), were evaluated. @*Results@#Ten patients were enrolled in the study. Their mean age was 70.1±9.7 years. Clinically, NRS-LBP, NRS-LP, and ODI before surgery were 5.1%, 7.5%, and 53.2%, respectively. The mean number of suspicious roots was 2.6±0.8. After RFSS, the mean number of symptomatic roots was 1.6±1.0. On average, 1.4 lumbar segments were decompressed. The follow-up period was 35.3±12.8 months. At the last follow-up, NRS-LBP, NRS-LP, and ODI were 3.1%, 1.5%, and 35.3%, respectively. There was no recurrence or need for further surgical treatment for lumbar stenosis. @*Conclusion@#RFSS is a potentially helpful diagnostic tool for verifying and localizing symptomatic injured root lesions, particularly in patients with multilevel spinal stenosis.

Repeated endotracheal tube cuff tears during nasotracheal intubation due to nasal cavity orthodontic micro-implant - A case report -

Background@#Nasotracheal intubation is generally performed for intraoral surgery.Case: A 34-year-old female patient who underwent orthognathic surgery exhibited repeated endotracheal tube cuff tears during nasotracheal intubation. After intubation, leaks developed, and torn endotracheal cuff was observed in the removed endotracheal tube. Subsequently, re-intubation through the same nasal cavity was performed immediately, but leakage from the torn endotracheal tube cuff was re-observed. A leakage test of the extubated tube revealed air bubbles and leaks near the tube cuff due to the tear. Nasotracheal intubation was performed through the other nasal cavity, and there were no leakage findings or abnormalities. During the course of the surgery, the surgeon noticed that the orthodontic micro-implant deposited in the mid-tube cavity was exposed to the nasal cavity. @*Conclusions@#We aimed to emphasize caution and discuss the possibility that orthodontic micro-implants that are not confirmed during preoperative evaluation may cause repeated endotracheal tube cuff tears.

Analysis of Gene Deficiency Types of Thalassemia in Lingui District of Guilin City / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene defect types and distribution characteristics of α- and β-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures.@*METHODS@#A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and β-thalassemia positive cases.@*RESULTS@#Among 6 496 suspected patients, 1 363 were thalassemia carriers, the total positive rate was 20.98%. There were 677 cases of single-gene deletion and 26 cases of double-gene detetion on the deletional α-thalassemia, 115 cases of non-deletion α-thalassemia mutation and 4 cases of deletion plus mutation. The positive rate of α-thalassemia was 12.66%. There were 11 gene abnormalities for α-thalassemia, of which --@*CONCLUSION@#Lingui district of Guilin city is a high incidence area of thalassemia. The mutation rate of α-thalassemia --

Exploration on mechanism of Weimaining in treatment of LUAD based on network pharmacology and molecular docking / 中国药理学通报

Aim To investigate the pharmacological mechanism of Weimaining in the treatment of lung ade¬nocarcinoma ( LUAD) , using a network pharmacology and molecular docking approach. Methods The active components and potential targets of Weimanin ( Rhizo- ma Fagopyri Cymosi) were screened out through TCM- SP, TCMID, BATMAN-TCM and ETCM data plat-form, and supplemented with literature. The gene ex¬pression data of LUAD were obtained from the Gen Ex¬pression Omnibus database(GEO) , and the differenti¬ally expressed genes were determined using R software. A protein-protein interaction( PPI) network of intersec¬tion targets was constructed by STRING and visualized by Cytoscape software, and GO functional annotation and KEGG pathway enrichment analysis were per¬formed by Metascape platform. Finally, molecular doc¬king studies were carried out to verify the binding of core components and targets. Results Selecting the OB and DL as filter condition, 16 active ingredients and 353 potential targets were involved. MMP-9, MMP-1, CAT and other targets were closely related to LUAD. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Fluid shear stress and athero¬sclerosis, Pathways in cancer, AGE-RAGE signaling pathway, p53 signaling pathway, etc. Conclusions The present study investigates the main active compo¬nents, targets and related pathways of Weimaining in the treatment of LUAD, which provides the theoretical basis and ideas for further research.

Pharmacological strategies to prevent postoperative delirium: a systematic review and network meta-analysis

Background@#Postoperative delirium (POD) is a condition of cerebral dysfunction and a common complication after surgery. This study aimed to compare and determine the relative efficacy of pharmacological interventions for preventing POD using a network meta-analysis (NMA). @*Methods@#We performed a systematic and comprehensive search to identify and analyze all randomized controlled trials until June 29, 2020, comparing two or more pharmacological interventions, including placebo, to prevent or reduce POD. The primary outcome was the incidence of POD. We performed a network meta-analysis and used the surface under the cumulative ranking curve (SUCRA) values and rankograms to present the hierarchy of the pharmacological interventions evaluated. @*Results@#According to the SUCRA value, the incidence of POD decreased in the following order: the combination of propofol and acetaminophen (86.1%), combination of ketamine and dexmedetomidine (86.0%), combination of diazepam, flunitrazepam, and pethidine (84.8%), and olanzapine (75.6%) after all types of anesthesia; combination of propofol and acetaminophen (85.9%), combination of ketamine and dexmedetomidine (83.2%), gabapentin (82.2%), and combination of diazepam, flunitrazepam, and pethidine (79.7%) after general anesthesia; and ketamine (87.1%), combination of propofol and acetaminophen (86.0%), and combination of dexmedetomidine and acetaminophen (66.3%) after cardiac surgery. However, only the dexmedetomidine group showed a lower incidence of POD than the control group after all types of anesthesia and after general anesthesia. @*Conclusions@#Dexmedetomidine reduced POD compared with the control group. The combination of propofol and acetaminophen and the combination of ketamine and dexmedetomidine seemed to be effective in preventing POD. However, further studies are needed to determine the optimal pharmacological intervention to prevent POD.

Immunohistochemical Analysis of Prurigo Nodularis in 209 Patients: Clinicopathological Analysis between Atopic and Non-Atopic Patients and between Treatment Response Groups

Background@#Prurigo nodularis (PN) is a highly pruritic disease that significantly impairs patient quality of life. Although the mechanism that causes pruritus is not clear, one hypothesis argues that neural hyperplasia, mast cell, and Merkel cell neurite complexes may be associated with PN pathogenesis. @*Objective@#The objective of this study was to analyze whether special staining outcomes differed depending on the presence of atopic dermatitis (AD) and treatment response. @*Methods@#A total of 209 patients diagnosed with PN was analyzed retrospectively. Patients were divided into two groups according to presence or past history of AD and by treatment response. Histopathologic features were obtained using the following stains: Giemsa, S-100, neuron-specific enolase, cytokeratin (CK)-20, CAM5.2, and CK8/CK18. @*Results@#A total of 126 patients (60.29%) had AD, and 68 (32.54%) showed clinical improvement. There were no statistically significant differences in the staining results between the PN groups with AD (PN c̅ AD) and without AD (PN s̅ AD). Additionally, there were no statistically significant differences in staining results between the improved and non-im-proved groups. @*Conclusion@#Implementing the special stains helped to identify PN pathogenesis. Because there were no statistically significant differences in the special stain results between the improved and non-improved groups, we conclude that mast cell proliferation, neural hyperplasia, and Merkel cell hyperplasia may not have a significant effect on treatment response.

Immunohistochemical Analysis of Prurigo Nodularis in 209 Patients: Clinicopathological Analysis between Atopic and Non-Atopic Patients and between Treatment Response Groups

Background@#Prurigo nodularis (PN) is a highly pruritic disease that significantly impairs patient quality of life. Although the mechanism that causes pruritus is not clear, one hypothesis argues that neural hyperplasia, mast cell, and Merkel cell neurite complexes may be associated with PN pathogenesis. @*Objective@#The objective of this study was to analyze whether special staining outcomes differed depending on the presence of atopic dermatitis (AD) and treatment response. @*Methods@#A total of 209 patients diagnosed with PN was analyzed retrospectively. Patients were divided into two groups according to presence or past history of AD and by treatment response. Histopathologic features were obtained using the following stains: Giemsa, S-100, neuron-specific enolase, cytokeratin (CK)-20, CAM5.2, and CK8/CK18. @*Results@#A total of 126 patients (60.29%) had AD, and 68 (32.54%) showed clinical improvement. There were no statistically significant differences in the staining results between the PN groups with AD (PN c̅ AD) and without AD (PN s̅ AD). Additionally, there were no statistically significant differences in staining results between the improved and non-im-proved groups. @*Conclusion@#Implementing the special stains helped to identify PN pathogenesis. Because there were no statistically significant differences in the special stain results between the improved and non-improved groups, we conclude that mast cell proliferation, neural hyperplasia, and Merkel cell hyperplasia may not have a significant effect on treatment response.

Effects of Three Handing-Three Points on Thickness of Myelin Sheath and Expression of Neuregulin 1 and Human Epidermal Growth Factor Receptor 2 after Sciatic Nerve Injury in Rats / 中国康复理论与实践

Objective:To explore the effect of Tuina of Three Handing-Three Points on the recovery of motor function, the expression of neuregulin (NRG) 1 and human epidermal growth factor receptor (ErbB) 2 in the injured point of sciatic nerve and L4-6 spinal cord, and the morphological change of myelin sheath at the injured point of sciatic nerve of rats. Methods:A total of 76 male Sprague-Dawley rats were randomly divided into normal group, sham operation group, model group and Tuina group with 19 rats in each group. The right side sciatic nerve was clamped to make model in the model group and Tuina group. The sham operation group exposed sciatic nerve only. Tuina group received Tuina on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with dialing, plucking and kneading using Tuina technique simulator. All of them were tested with Oblique Plate Test before modeling, seven days and 28 days after modeling. Western blotting was used to detect the protein expression of NRG1 and ErbB2 in the injured point of sciatic nerve and L4-6 spinal cord. The change of myelin sheath at the sciatic nerve injury point was observed and analyzed by transmission electron microscope. Results:Seven days and 28 days after modeling, the scores of Oblique Plate Test were lower in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); 28 days after modeling, the scores was higher in Tuina group than in the model group (P < 0.05). At the sciatic nerve injury point, three days after modeling, the expression of NRG1 and ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); seven days and 28 days after modeling, there was no significant difference in NRG1 among groups (P > 0.05); 28 days after modeling, the expression of ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05). In L4-6 spinal cord, three days after modeling, the expression of NRG1 and ErbB2 was higher in the model group and Tuina group than in the normal group and sham operation group (P < 0.05); seven days after modeling, the expression of NRG1 was higher in the model group and Tuina group than in the sham operation group (P < 0.05), and the expression of ErbB2 was higher in the model group and Tuina group than in the normal group and the sham operation group (P < 0.05); 28 days after modeling, the expression of NRG1 was higher in Tuina group than in the model group (P < 0.05), and there was no significant difference in ErbB2 among groups (P > 0.05). The electron microscope showed that, 28 days after modeling, the myelin sheath collapsed seriously in the model group; while the ultrastructure of the nerve injury point improved, and the myelin sheath of the nerve fiber was relatively intact in Tuina group; the g-ratio value was lower in the model group than in the sham operation group (P < 0.05), the g-ratio value was higher in Tuina group than in the model group (P < 0.05), and no difference was found in g-ratio value between Tuina group and sham operation group (P > 0.05). Conclusion:Three Handing-Three Points could improve the motor function of hind limbs in rats with sciatic nerve injury, which may be related to the adjustment of NRG1 and ErbB2 in the sciatic nerve and spinal cord, to maintain normal myelin sheath structure.

Effects of Three Handing-Three Points on Motor Function and Expression of Transforming Growth Factor-β1/Smad2 Pathway in Injured Sciatic Nerve of Rats / 中国康复理论与实践

Objective:To investigate the effect of Tuina of Three Handing-Three Points on the motor function of hind limbs, the proliferation of Schwann cell, recovery of myelin sheath and the expression of transforming growth factor (TGF)-β1/Smad2 pathway protein in injured sciatic nerve of rats. Methods:A total of 66 male Sprague-Dawley rats were randomly divided into sham operation group (n = 22), model group (n = 22) and observation group (n = 22). The sciatic nerve injury model was made by clamping method. On the eighth day after modeling, the observation group received stimulation on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34). The sciatic functional index (SFI) was measured before intervention and 21 days after intervention. The Oblique Plate Test was performed before intervention, and seven days, 14 days and 21 days after intervention. The expression of S100, TGF-β1 and Smad2 were observed by immunofluorescence. The expression of TGF-β1, Smad2 and p-Smad2 was detected by Western blotting. Results:Before intervention, SFI was lower in the model group and observation group than in the sham operation group (P < 0.05); 21 days after intervention, SFI and the angle of Oblique Plate Test were higher in the observation group than in the model group (P < 0.05). Immunofluorescence showed that, 21 days after intervention, the expression of S100 was lower in the model group than in the sham operation group (P < 0.01), and was higher in the observation group than in the model group (P < 0.05), no difference was found between the observation group and the sham operation group (P > 0.05). Western blotting showed that, before intervention and seven days after intervention, the expression of TGF-β1, Smad2 and p-Smad2 were higher in the model group than in the sham operation group; 21 days after intervention, no difference was found in the expression among groups (P > 0.05) Conclusion:Three Handing-Three Points could promote the proliferation of Schwann cell and the recovery of myelin sheath, to improve the motor function of hind limbs in rats with sciatic nerve injury, which may not be related to TGF-β1/Smad2 pathway.

Effect of Three Handing-Three Points on Pain Function and Expression of CX3CL1/CX3CR1 in Spinal Cord Dorsal Horn of Rats with Sciatic Nerve Injury / 中国康复理论与实践

Objective:To investigate the mechanism of Three Handing-Three Points on pain function in sciatic nerve injury rats by observing the changes of chemokine (C-X3-C motif) ligand 1, CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) protein and mRNA expression in spinal dorsal horn. Methods:A total of 74 male Sprague-Dawley rats were randomly divided into normal group (n= 12), sham group (n = 24), model group (n = 25), and Three Handing-Three Points group (Tuina group,n = 13). The model group and Tuina group prepared the sciatic nerve injury model. The sham group exposed sciatic nerve only. Tuina group received Tuina on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with Tuina manipulation emulator. The photothermal pain threshold was measured seven days after modeling and after 20 days of intervention; cumulative pain score was measured seven days after modeling, and after ten days and 20 days of intervention. The spinal dorsal horn tissues were extracted to detect the protein and mRNA expression of CX3CL1/CX3CR1 with Western blotting and RT-PCR seven days after modeling and after 20 days of intervention. The microglia morphology in spinal dorsal horn was observed with immunofluorescence after 20 days of intervention. Results:Seven days after modeling, compared with the normal group, the photothermal pain tolerance threshold increased in the model group and the sham group (P < 0.05); compared with the sham group, the cumulative pain score increased in the model group and Tuina group (P < 0.05). After ten days of intervention, the cumulative pain score was lower in Tuina group than in the model group (P < 0.05). After 20 days of intervention, both the photothermal pain tolerance threshold and cumulative pain score were lower in Tuina group than in the model group (P < 0.05). There was no significant difference in the expression of CX3CL1/CX3CR1 protein and mRNA on the seven days after modeling and after 20 days of intervention (P > 0.05). The microglia in the model group were partially activated or completely activated, while those in Tuina group were unactivated or partially activated after 20 days of intervention. Conclusion:Three Handing-Three Points can improve the pain function of sciatic nerve injured rats, which may associate with regulating microglia through the pathway other than CX3CL1/CX3CR1.

Role of potassium channels in female reproductive system

Potassium channels are widely expressed in most types of cells in living organisms and regulate the functions of a variety of organs, including kidneys, neurons, cardiovascular organs, and pancreas among others. However, the functional roles of potassium channels in the reproductive system is less understood. This mini-review provides information about the localization and functions of potassium channels in the female reproductive system. Five types of potassium channels, which include inward-rectifying (Kir), voltage-gated (Kv), calcium-activated (KCa), 2-pore domain (K2P), and rapidly-gating sodium-activated (Slo) potassium channels are expressed in the hypothalamus, ovaries, and uterus. Their functions include the regulation of hormone release and feedback by Kir6.1 and Kir6.2, which are expressed in the luteal granulosa cells and gonadotropin-releasing hormone neurons respectively, and regulate the functioning of the hypothalamus–pituitary–ovarian axis and the production of progesterone. Both channels are regulated by subtypes of the sulfonylurea receptor (SUR), Kir6.1/SUR2B and Kir6.2/SUR1. Kv and Slo2.1 affect the transition from uterine quiescence in late pregnancy to the state of strong myometrial contractions in labor. Intermediate- and small-conductance KCa modulate the vasodilatation of the placental chorionic plate resistance arteries via the secretion of nitric oxide and endothelium-derived hyperpolarizing factors. Treatment with specific channel activators and inhibitors provides information relevant for clinical use that could help alter the functions of the female reproductive system.

Role of potassium channels in female reproductive system

Potassium channels are widely expressed in most types of cells in living organisms and regulate the functions of a variety of organs, including kidneys, neurons, cardiovascular organs, and pancreas among others. However, the functional roles of potassium channels in the reproductive system is less understood. This mini-review provides information about the localization and functions of potassium channels in the female reproductive system. Five types of potassium channels, which include inward-rectifying (Kir), voltage-gated (Kv), calcium-activated (KCa), 2-pore domain (K2P), and rapidly-gating sodium-activated (Slo) potassium channels are expressed in the hypothalamus, ovaries, and uterus. Their functions include the regulation of hormone release and feedback by Kir6.1 and Kir6.2, which are expressed in the luteal granulosa cells and gonadotropin-releasing hormone neurons respectively, and regulate the functioning of the hypothalamus–pituitary–ovarian axis and the production of progesterone. Both channels are regulated by subtypes of the sulfonylurea receptor (SUR), Kir6.1/SUR2B and Kir6.2/SUR1. Kv and Slo2.1 affect the transition from uterine quiescence in late pregnancy to the state of strong myometrial contractions in labor. Intermediate- and small-conductance KCa modulate the vasodilatation of the placental chorionic plate resistance arteries via the secretion of nitric oxide and endothelium-derived hyperpolarizing factors. Treatment with specific channel activators and inhibitors provides information relevant for clinical use that could help alter the functions of the female reproductive system.

Effect of intraperitoneally administered propentofylline in a rat model of postoperative pain

Background@#In this study, we sought to evaluate whether systemic propentofylline (PPF) has antiallodynic effects in a rat model of postoperative pain, and to assess the mechanism involved. @*Methods@#After plantar incision, rats were intraperitoneally injected with various doses of PPF to evaluate its antiallodynic effect. To investigate the involved mechanism, rats were intraperitoneally injected with yohimbine, dexmedetomidine, prazosin, naloxone, atropine or mecamylamine, following the incision of the rat hind paws, and then PPF was administered intraperitoneally. The mechanical withdrawal threshold (MWT) was evaluated using von Frey filaments at various time points and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured to determine the inflammatory response level. @*Results@#MWT was significantly increased after intraperitoneal injection of 30 mg/ kg of PPF when compared with the control group. Injection of PPF and yohimbine, atropine or mecamylamine showed significant decreases in the MWT, while injection of PPF and dexmedetomidine showed a significant increase. Systemic administration of PPF inhibited the post-incisional increase in serum level of TNF-α and IL-1β. @*Conclusions@#Systemic administration of PPF following surgery presented antiallodynic effects in a rat model of postoperative pain. The antiallodynic effects against mechanical allodynia could be mediated by α-adrenergic and cholinergic receptors.

Beneficial Effect of Chloroquine and Amodiaquine on Type 1 Diabetic Tubulopathy by Attenuating Mitochondrial Nox4 and Endoplasmic Reticulum Stress

Background@#Oxidative stress induced by chronic hyperglycemia is recognized as a significant mechanistic contributor to the development of diabetic kidney disease (DKD).Nonphagocytic nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in many cell types and in the kidney tissue of diabetic animals. We designed this study to explore the therapeutic potential of chloroquine (CQ) and amodiaquine (AQ) for inhibiting mitochondrial Nox4 and diabetic tubular injury. @*Methods@#Human renal proximal tubular epithelial cells (hRPTCs) were cultured in highglucose media (30 mM D-glucose), and diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57BL/6J mice. CQ and AQ were administered to the mice via intraperitoneal injection for 14 weeks. @*Results@#CQ and AQ inhibited mitochondrial Nox4 and increased mitochondrial mass in hRPTCs under high-glucose conditions. Reduced mitochondrial ROS production after treatment with the drugs resulted in decreased endoplasmic reticulum (ER) stress, suppressed inflammatory protein expression and reduced cell apoptosis in hRPTCs under high-glucose conditions. Notably, CQ and AQ treatment diminished Nox4 activation and ER stress in the kidneys of STZ-induced diabetic mice. In addition, we observed attenuated inflammatory protein expression and albuminuria in STZ-induced diabetic mice after CQ and AQ treatment. @*Conclusion@#We substantiated the protective actions of CQ and AQ in diabetic tubulopathy associated with reduced mitochondrial Nox4 activation and ER stress alleviation. Further studies exploring the roles of mitochondrial Nox4 in the pathogenesis of DKD could suggest new therapeutic targets for patients with DKD.

Chronic Exfoliative Cheilitis Successfully Treated by Pinhole Method Using CO₂ Laser

No abstract available.

A Case of Nivolumab-Induced Lichen Planus

No abstract available.

Modulation of Dopaminergic Neuronal Excitability by Zinc through the Regulation of Calcium-related Channels

Depending on the intracellular buffering of calcium by chelation, zinc has the following two apparent effects on neuronal excitability: enhancement or reduction. Zinc increased tonic activity in the depolarized state when neurons were intracellularly dialyzed with EGTA but attenuated the neuronal activity when BAPTA was used as an intracellular calcium buffer. This suggests that neuronal excitability can be modulated by zinc, depending on the internal calcium buffering capacity. In this study, we elucidated the mechanisms of zinc-mediated alterations in neuronal excitability and determined the effect of calcium-related channels on zinc-mediated alterations in excitability. The zinc-induced augmentation of firing activity was mediated via the inhibition of small-conductance calcium-activated potassium (SK) channels with not only the contribution of voltage-gated L-type calcium channels (VGCCs) and ryanodine receptors (RyRs), but also through the activation of VGCCs via melastatin-like transient receptor potential channels. We suggest that zinc modulates the dopaminergic neuronal activity by regulating not only SK channels as calcium sensors, but also VGCCs or RyRs as calcium sources. Our results suggest that the cytosolic calcium-buffering capacity can tightly regulate zinc-induced neuronal firing patterns and that local calcium-signaling domains can determine the physiological and pathological state of synaptic activity in the dopaminergic system.