RESUMEN
Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.
RESUMEN
Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC50 at 3.5 ± 1.5 µM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 µM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 µM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 µM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg-1· d-1, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 µM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.
Asunto(s)
Analgésicos/uso terapéutico , Fluorobencenos/uso terapéutico , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Neuralgia/tratamiento farmacológico , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéutico , Potenciales de Acción/efectos de los fármacos , Animales , Formaldehído , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Cobayas , Células HEK293 , Humanos , Inflamación/inducido químicamente , Inflamación/complicaciones , Masculino , Ratones Endogámicos C57BL , Neuralgia/inducido químicamente , Neuralgia/etiología , Neuronas/efectos de los fármacos , Nervios Espinales/lesionesRESUMEN
With the purpose of identifying novel selective κ opioid receptor (KOR) antagonists as potential antidepressants from nepenthone analogues, starting from N-nor-N-cyclopropylmethyl-nepenthone (SLL-020ACP), a highly selective and potent KOR agonist, a series of 7ß-methyl-nepenthone analogues was conceived, synthesized and assayed on opioid receptors based on the concept of hybridization. According to the pharmacological results, the functional reversal observed in orvinol analogues by introduction of 7ß-methyl substituent could not be reproduced in nepenthone analogues. Alternatively, introduction of 7ß-methyl substituent was associated with substantial loss of both subtype selectivity and potency but not efficacy for nepenthone analogues, which was not found in 7ß-methyl orvinol analogues. Surprisingly, SLL-603, a 7ß-methyl analogue of SLL-020ACP, was identified to be a KOR full agonist. The possible molecular mechanism for the heterogeneity in activity cliff was also investigated. In conclusion, 7ß-methyl substituent was a structural locus associated with activity cliff and demonstrated as a pharmacological heterogeneity between nepenthone and orvinol analogues that warrants further investigations.
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Morfinanos/farmacología , Receptores Opioides kappa/agonistas , Animales , Células CHO , Células Cultivadas , Cricetulus , Relación Dosis-Respuesta a Droga , Modelos Moleculares , Estructura Molecular , Morfinanos/síntesis química , Morfinanos/química , Relación Estructura-ActividadRESUMEN
ETHNO-PHARMACOLOGICAL RELEVANCE: Hibiscus rosa-sinensis L. (HRS), a folk medicine named Zhujin in China, possess anti-tumor, antioxidant, antibacterial, low density lipoprotein oxidation prevention and macrophage death prevention effects. The leaves and red flowers of HRS have been traditionally used to treat with furuncle and ulceration. AIM OF THE STUDY: To investigate the efficacy and possible mechanism of the N-butyl alcohol extract of HRS (NHRS) red flowers in wound healing by analyzing the collagen fiber deposition, angiogenic activity and macrophages action of the NHRS. MATERIALS AND METHODS: In an excisional wound healing model in rats, different concentrations of NHRS, or recombinant bovine basic fibroblast growth factor (rbFGF), were respectively applied twice daily for 9 days. Histopathology was assessed on day 9 via hematoxylin and eosin (HE) and Masson's trichrome (MT) staining, and immunohistochemistry for vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1) and CD68. Immunomodulation by NHRS was evaluated by a carbon clearance test in mice. RESULTS: Wound healing post-surgery was greater in the rbFGF-control, NHRS-M and MHRS-H groups than in the model and 5% dimethylsulfoxide (DMSO)-control groups after the third day. By the sixth day the wound contraction of NHRS-M and MHRS-H groups was much higher than the rbFGF-control group. HE and MT staining revealed that epithelialization, fibroblast distribution, collagen deposition of NHRS-M- and NHRS-H-control groups were significantly higher than the model group. Moreover, immunohistochemistry showed more intense staining of VEGF, TGF-ß1 and CD68 in the rbFGF- and NHRS-control groups, compared to that in model and 5% DMSO-control groups. The clearance and phagocytic indices of NHRS-M- and NHRS-H-control groups were significantly higher than that of the carboxyl methyl cellulose (CMC) group in mice. CONCLUSION: NHRS accelerates wound repair via enhancing the macrophages activity, accelerating angiogenesis and collagen fiber deposition response mediated by VEGF and TGF-ß1.
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Hibiscus/química , Neovascularización Fisiológica/efectos de los fármacos , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , 1-Butanol/química , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Bovinos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Factor 2 de Crecimiento de Fibroblastos/farmacología , Flores , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To evaluate the efficacy of multimodal-antiemetic therapy on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopy. METHODS: 129 patients scheduled for gynecological laparoscopy were randomly allocated to a multimodal-antiemetic group (group M, with 65 cases) or an ondansetron control group (group C, with 64 cases). In group M patients received a target-controlled infusion of propofol and remifentanil, prophylactic dexamethasone 10 mg and tropisetron 4 mg were given and parecoxib sodium 40 mg was used 30 minutes before the end of surgery. In group C patients received sevoflurane and 50% nitrous oxide. Prophylactic ondansetron 4 mg was given to patients 30 min before the end of surgery. The incidence of nausea and vomiting, use of rescue antiemetic drugs were recorded for 24 h. RESULTS: 24 h after surgery, the incidence of patients who suffered PONV was significantly lower in Group M compared with Group C (29% vs 70%, P < 0.05). At 0 - 2 h, 2 - 6 h, 6 - 24 h after surgery, the incidences of PONV were 8%, 6% and 25% for group M respectively, significantly lower than those for group C, which were 33%, 30% and 66% respectively(P < 0.05). CONCLUSIONS: Multimodal-antiemetic therapy; a regimen including total intravenous anaesthesia with propofol and remifentanil, prophylactic antiemetic (dexamethasone at induction and tropisetron at end of surgery), and multimodal analgesia with parecoxib sodium could significantly reduce the incidence of PONV after gynecological laparoscopy.
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Antieméticos/uso terapéutico , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Laparoscopía/efectos adversos , Ondansetrón/uso terapéutico , Náusea y Vómito Posoperatorios/terapia , Adulto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: to evaluate clinical efficacy and safety of levornidazole in the treatment of pelvic anaerobic infections. METHODS: a multicenter randomized controlled clinical study was conducted to evaluate clinical efficacy and safety of levornidazole. One hundred and fourty-three patients with pelvic anaerobic bacteria infection were classified into 70 cases treated by levornidazole in study group and 73 cases treated by Ornidazole in control group. Those patients in two groups were both administered at a dose of 0.5 g twice daily for 5 - 7 days. The rate of clinical efficacy, bacteria clearance and adverse effect were recorded and compared between two groups. RESULTS: at the endpoint, the rate of clinical efficacy were 80% (56/70) in study group and 81% (59/73) in control group, which did not reach significant difference (P > 0.05). The rate of bacteria clearance were 97% (36/37) in study group and 92% (22/24) in control group, which also did not reach significant difference (P > 0.05). The rate of adverse reaction of 3% (20/70) in study group was significantly lower than 22% (16/73) in control group (P < 0.05). CONCLUSION: it is effective and safe to treat pelvic anaerobic infections with levornidazole and sodium chloride injection.
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Antiinfecciosos/uso terapéutico , Bacterias Anaerobias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Ornidazol/uso terapéutico , Infección Pélvica/tratamiento farmacológico , Adolescente , Adulto , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Infecciones Bacterianas/microbiología , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravenosas , Persona de Mediana Edad , Ornidazol/administración & dosificación , Ornidazol/efectos adversos , Infección Pélvica/microbiología , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio/efectos adversos , Cloruro de Sodio/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To investigate whether extracellular signal-regulated kinase 1 (ERK(1)) is activated and associated with hepatic stellate cell (HSC) proliferation in fibrotic rat liver tissue. METHODS: Rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and Masson's trichrome method. ERK(1) mRNA in rat liver tissue was determined by reverse transcription-polymerase chain reaction, while the distribution of ERK(1) was assessed by immunohistochemistry. ERK(1) protein was detected by Western blotting analysis. The number of activated HSCs was quantified after alpha smooth muscle actin (alpha-SMA) staining. RESULTS: With the development of hepatic fibrosis, the positive staining cells of alpha-SMA increased obviously, and mainly resided in the portal ducts. Fiber septa and perisinuses were accompanied with proliferating bile ducts. The positive staining areas of the rat livers in model groups 1-4 wk after ligation of common bile duct (12.88% +/- 2.63%, 22.65% +/- 2.16%, 27.45% +/- 1.86%, 35.25% +/- 2.34%, respectively) were significantly larger than those in the control group (5.88% +/- 1.46%, P < 0.01). With the development of hepatic fibrosis, the positive cells of ERK(1) increased a lot, and were mainly distributed in portal ducts, fiber septa around the bile ducts, vascular endothelial cells and perisinusoidal cells. Western blotting analysis displayed that the expression of ERK(1) and ERK(2) protein was up-regulated during the model course, and its level was the highest 4 wk after operation, being 3.9-fold and 7.2-fold higher in fibrotic rat liver than in controls. ERK(1) mRNA was expressed in normal rat livers as well, which was up-regulated two days after BDL and reached the highest 4 wk after BDL. The expression of ERK(1) was positively correlated with alpha-SMA expression (r = 0.958, P < 0.05). CONCLUSION: The expression of ERK(1) protein and mRNA is greatly increased in fibrotic rat liver tissues, which may play a key role in HSC proliferation and hepatic fibrogenesis.