Research progress on pathogenesis and treatment of drug-resistant epilepsy / 药学学报

Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.

Rutaecarpine inhibited imiquimod-induced psoriasis-like dermatitis via inhibiting the NF-κB and TLR7 pathways in mice.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. As psoriasis rarely occurs in nonhuman animals, the lack of an ideal animal model reflecting the histopathological and molecular immunological characteristics of psoriasis remains an urgent issue. In the present study, an imiquimod-induced psoriasis-like dermatitis mouse model was constructed under natural immune conditions and verified by evaluations of the Psoriasis Area and Severity Index (PASI) score and Baker score, H&E staining, immunohistochemical examination of the CD3 and Gr1 levels, measurement of plasmacytoid dendritic cell- (pDC) and Th17-associated cytokine levels, and evaluation of p65 phosphorylation and TLR7 expression. Moreover, rutaecarpine (RUT), the main active ingredient in the traditional Chinese medicine Wu-Zhu-Yu, could improve psoriasis-like dermatitis through effects on pDC- and Th17-associated cytokines through NF-κB and toll-like receptor 7 (TLR7) signaling. Taken together, the imiquimod-induced psoriasis-like dermatitis mouse model can be regarded as an ideal model for evaluating psoriasis pathogenesis and antipsoriatic drugs. We provided theoretical and experimental evidence for the clinical application of RUT in psoriasis.

Effects of Ultra-early Hyperbaric Oxygen Therapy on Femoral Calcitonin Gene-Related Peptide and Bone Metabolism of Rats With Complete Spinal Transection.

STUDY DESIGN: Seventy-five Sprague-Dawley rats were randomly divided into sham, complete spinal cord transection (CSCT) and hyperbaric oxygen (HBO) groups. Among them, rats in HBO group were further divided into 3 hours group (HBO1) and 12 hours group (HBO2). OBJECTIVE: To study the effects of ultra-early HBO therapy on femoral calcitonin gene-related peptide (CGRP) and bone metabolism of rats with CSCT. SUMMARY OF BACKGROUND DATA: Complete spinal cord injury (SCI) is still an unresolved problem in clinical practice. Studies on changes in (calcitonin gene-related peptide) CGRP and bone metabolism and osteoporosis prevention after SCI have important clinical significance. METHODS: Rats in the sham group underwent laminectomy alone, whereas rats in the other three groups underwent laminectomy and CSCT at the level of the 10th thoracic vertebra. Six weeks after operation, rat blood samples and femoral samples from CSCT area were taken and prepared for immunohistochemical staining of CGRP, quantitative polymerase chain reaction (qPCR) of CGRP mRNA, enzyme-linked immunosorbent assay (ELISA) for the levels of serum bone-specific alkaline phosphatase (sBAP), serum osteocalcin (sOC), serum type-I collagen amino-terminal peptide (sNTX), and urinary deoxypyridinoline (uDPD). These data were statistically analyzed using paired LSD or Tamhane. RESULTS: The number of CGRP-positive cells and expression of CGRP mRNA in femur were significantly reduced, and the levels of sBAP, sOC, sNTX, and uDPD were significantly increased in CSCT, HBO1, and HBO2 groups than in the sham group, (P < 0.05-0.01). In addition, the number of CGRP-positive cells, expression of CGRP mRNA in femur, and the levels of sBAP and sOC were significantly enhanced, but the levels of sNTX and uDPD were significantly lowered in HBO1 group than in HBO2 and CSCT groups (P < 0.05). CONCLUSION: Ultra-early HBO therapy could improve bone turnover, promote bone formation, and prohibit bone resorption by enhancing CGRP synthesis in the sensory neurons in posterior horn of spinal cord. LEVEL OF EVIDENCE: N/A.

Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling.

Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Treatment of human umbilical vein endothelial cells (HUVECs) with ASA VI (20-80 µg/mL) dose-dependently promoted the proliferation, migration and enhanced their angiogenic ability in vitro, which were associated with the up-regulated HIF-1α/VEGF signaling. Full-thickness cutaneous wound model rats were injected with ASA VI (20 mg·kg-1·d-1, iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound healing, and more blood vessels were observed in the regenerated tissue. Due to rapid vascularization, the cellular proliferation status, granulation tissue formation, collagen matrix deposition and remodeling processes were all accelerated, resulting in efficient wound healing. In summary, ASA VI promotes angiogenesis of HUVECs in vitro via up-regulating the HIF-1α/VEGF pathway, and efficiently enhances the vascularization in regenerated tissue and facilitates wound healing in vivo. The results reveal that ASA VI is a potential therapeutic for vessel injury-related wounds.

Impacts of Ultra-early Hyperbaric Oxygen Therapy on Bone Mass of Rats With Complete Spinal Cord Transection.

STUDY DESIGN: Seventy-five SD rats were randomly assigned to four groups: sham-operated group (Sham, n = 15), complete spinal cord transection (CSCT, n = 20) group, hyperbaric oxygenation group 1 (HBO1, n = 20), and hyperbaric oxygenation group 2 (HBO2, n = 20). OBJECTIVE: The aim of this study was to analyze the impacts of ultra-early hyperbaric oxygen therapy on bone mass of rats with CSCT. SUMMARY OF BACKGROUND DATA: Treatment of patients with complete SCI is still an unresolved medical issue and needs to be further investigated. Studies on changes in bone mass as well as osteoporosis prevention after SCI have important clinical significance. METHODS: Rats in the sham group only underwent T10 laminectomy, without damaging the spinal cord. Rats in CSCT, HBO1, and HBO2 groups underwent T10 laminectomy and spinal cord transection at T10 level. Rats in HBO1 and HBO2 groups received three courses of hyperbaric oxygen therapy with 10 days per course starting at 3 and 12 hours after spinal cord injury, respectively. The femoral biomechanical characteristics, the bone calcium, and the bone hydroxyproline (B-HYP) contents were determined. Morphology of the femur bone trabecula and the bone collagen were observed by HE staining and by masson triad color staining, respectively. RESULTS: After 6 weeks of treatment, rats in the CSCT group showed significant decreases in femur structural and material mechanics parameters, calcium and B-HYP contents, (P < 0.01), as well as sparse, fractured, malaligned trabecular bone and collagen compared with rats in the sham group. After treatments, compared with rats in the CSCT and HBO2 groups, rats in HBO1 group showed enhancement in femur structural and material mechanics parameters, calcium and B-HYP contents, (P < 0.05), as well as trabecular bone and collagen with better continuity and neater arrangement. CONCLUSION: Ultra-early HBO therapy can significantly improve bone mass in CSCT rats. LEVEL OF EVIDENCE: N/A.

Arbuscular mycorrhizal fungi community structure, abundance and species richness changes in soil by different levels of heavy metal and metalloid concentration.

Arbuscular Mycorrhizal Fungi (AMF) play major roles in ecosystem functioning such as carbon sequestration, nutrient cycling, and plant growth promotion. It is important to know how this ecologically important soil microbial player is affected by soil abiotic factors particularly heavy metal and metalloid (HMM). The objective of this study was to understand the impact of soil HMM concentration on AMF abundance and community structure in the contaminated sites of South Korea. Soil samples were collected from the vicinity of an abandoned smelter and the samples were subjected to three complementary methods such as spore morphology, terminal restriction fragment length polymorphism (T-RFLP) and denaturing gradient gel electrophoresis (DGGE) for diversity analysis. Spore density was found to be significantly higher in highly contaminated soil compared to less contaminated soil. Spore morphological study revealed that Glomeraceae family was more abundant followed by Acaulosporaceae and Gigasporaceae in the vicinity of the smelter. T-RFLP and DGGE analysis confirmed the dominance of Funneliformis mosseae and Rhizophagus intraradices in all the study sites. Claroideoglomus claroideum, Funneliformis caledonium, Rhizophagus clarus and Funneliformis constrictum were found to be sensitive to high concentration of soil HMM. Richness and diversity of Glomeraceae family increased with significant increase in soil arsenic, cadmium and zinc concentrations. Our results revealed that the soil HMM has a vital impact on AMF community structure, especially with Glomeraceae family abundance, richness and diversity.

Acupuncture for adolescents with mild-to-moderate myopia: study protocol for a randomized controlled trial.

BACKGROUND: Myopia is a public health problem worldwide and its incidence increases with age. The use of acupuncture to treat myopia is a common practice in China, however, the use of acupuncture to treat myopia is disputed in other parts of the world. This study aims to determine the safety of acupuncture to treat myopia and its efficacy over six months. METHODS/DESIGN: A randomized, parallel, single-center, assessor- and statistician-blinded, controlled clinical trial will be performed. A total of 100 teenagers, between seven and 12 years of age, with mild-to-moderate myopia and spherical lenses <-6.00 D and cylindrical lenses <-1.50 D will be selected from the Xinjiang Uygur Autonomous Region Institute of Traditional Chinese Medicine, a grade III level A teaching hospital in Urumqi, Xinjiang, China (Xinjiang Medical University Affiliated Hospital of Traditional Medicine). The subjects will be randomly assigned to two different groups (control and acupuncture groups), each group containing 50 subjects. The subjects in both groups wear single-vision corrective lenses. In the acupuncture group, acupuncture will be performed daily for nine consecutive days on five points (bilateral Cuanzhu, Tongziliao, Sibai, Muchuang, and Hegu), followed by no treatment for one day. Six cycles of treatment will be undertaken continuously for a total of 60 days. Following 60 days of treatment, a follow-up period of six months will be included. The primary outcome will be diopter determination. The secondary outcomes will include distance visual acuity, axial length, lens thickness, ciliary body thickness, and subjective symptoms of the eyes and entire body. The main time points for the evaluation of clinical efficacy will be the first, third, and sixth months after treatment. DISCUSSION: This study will provide clinical observations of various indices following the use of acupuncture to treat adolescents with mild-to-moderate myopia, as well as information on the safety of acupuncture. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-13003448; registration date: 7 August 2013).

Effects of ultra-early stage hyperbaric oxygenation on the hind limb bone mineral density in rats after complete spinal cord transection.

AIM: To study the effects of ultra-early stage hyperbaric oxygenation on the hind limb bone mineral density in rats after complete spinal cord transection. METHODS: 55 SD rats were randomly assigned into three groups: sham-operated group (Sham); complete spinal cord transection. (CSCT) group; and hyperbaric oxygenation (HBO2) group. Three hours after surgery, the HBO2 group started receiving hyperbaric oxygen therapy. Bone mineral density (BMD) of total femur, total tibia and their subregions in vitro was measured with dual-energy X-ray absorptiometry (DEXA). RESULTS: After the six-week treatment, BMD of total femur, BMD in regions1-2 at the distal femur, BMD in regions 6-7 at the proximal femur and BMD in regions 1-2 at the proximal tibia in vitro were markedly decreased in CSCT group at six weeks post-operation compared with that in the sham-operated group (p < 0.05-0.01). Also, in the HBO2 group, BMD value of total femur in vitro was significantly higher than that in CSCT group (p < 0.05). CONCLUSION: Ultra-early stage hyperbaric oxygenation alleviates the hind limb bone loss in femur bone in rats following complete spinal cord transection.

[Effect of ultra-early hyperbaric oxygenation on spinal edema and hind limb motor function in rats with complete spinal cord transection].

OBJECTIVE: To evaluate the effect of ultra-early hyperbaric oxygenation on spinal edema and hind limb motor function in rats with complete spinal cord transection. METHODS: Fifty-five healthy 3-month-old female SD rats were randomly divided into sham-operated group (n=15), complete spinal cord transection group (CSCT group, n=20) and hyperbaric oxygen group (HBO group, n=20). The rats in the sham-operated group underwent only laminectomy, while those in the other 2 groups underwent CSCT at the T10 level. The rats in HBO group were placed in an oxygen chamber 3 h after the operation for 10 days as a treatment course, and 3 treatment courses were administered at the interval of 6 days. In the first treatment course, 2 hyperbaric oxygenation sessions were given daily, and in the following 2 course, only 1 session was given daily. The recovery of hindlimb motor function was evaluated using the open-field Basso-Beattie-Bresnahan (BBB) scoring system once a week for 6 weeks. All the rats were sacrificed 6 weeks after the operation to measure the water content in the injured tissues. RESULTS: The BBB scores of CSCT group and HBO group gradually increased with the passage of time after the operation, and from week 2 to week 6, HBO group had significantly higher scores than CSCT group (P<0.05). The water content was markedly increased in CSCT group at 6 weeks after the operation as compared with that in the sham-operated group (P<0.01), and significantly reduced in HBO group in comparison with that in the CSCT group (P<0.05). CONCLUSION: Ultra-early HBO can suppress spinal cord edema and promote hindlimb locomotor recovery in rats with complete spinal cord transection.

Effects of vitamin C and E on the ultrastructure in liver, kidney and brain of fluorosis rats / 中国地方病学杂志

Objective To observe the effects of vitamin C (VC) and E (VE) on the uhrastrueture of liver, kidney and brain tissue of fluorosis rats. Methods One hundred and twenty Wistar rats were chosen as the experimental animals and were divided into 9 groups randomly. The control group were given distilled water and the fluoride exposed group were given distilled water containing sodium fluoride 150 mg/L. The throe VC-fluoride exposed groups were given VC orally in a dose of 50,100,150 mg·kg-1.d-1, respectively, and the three VE-fluoride exposed groups were given VE of 25,50,75 mg·kg-1·d-1, respectively. The VC-VE-fluoride exposed group were given VC of 100 mg·kg-1·d-1and VE of 50 mg·kg-1·d-1at the same time of high fluoride water intake. The rats were sacrificed after 9 months and the ultrastructure changes on liver, kidney and brain tissues of each group were observed under transmission electron microscope(TEM). Results The uhrastrueture of liver, kidney and brain showed pathologic changes in the rats that drank water containing high eoneentrations of sodium fluoride. ①Edema of hepatocytes, smeared mitochontria and nuclear matrix, lipid droplet in eytoplasm of hepatocytes, margination of nueleohs as well as obvious swelling of liver sinusoidal endothelial were observed in fluoride exposed group. ② There were marginafion of heterochromatin, expansion of cell space and endoplasmic reticulum in the kidney after the exposure to excess fluoride.③Signifieant changes were found on glial eells on the brain, including cell swelling, increase and marginafion of heterochromatin in the fluoride exposure group. There were no significant uhrastrueture changes in the VC or VE intervention group, while the VC-VE-fluoride exposure group was almost the same as the control group. Conclusions Fluoresis may cause damage on liver, kidney and brain in rats. VC and VE, alone or combined, have protective effects, and the combined supplementation was stronger than single supplementations.