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1.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3288-3294, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-39041091

RESUMEN

This study aimed to explore the regulating effect of Gegen Decoction(GGD) on the hypothalamic-pituitary-ovarian axis(HPOA) dysfunction in the mouse model of primary dysmenorrhea(PD). The mouse model of PD with periodic characteristics was established by administration of estradiol benzoate and oxytocin. Mice were randomized into control, model, GGD, and ibuprofen groups. The writhing response, hypothalamus index, pituitary index, ovary index, and uterus index were observed and determined. The serum levels of prostaglandin F_(2α)(PGF_(2α)), gonadotropin-releasing hormone(GnRH), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and estrogen(E_2) levels were measured by ELISA kits. Western blot and qPCR were employed to determine the protein and mRNA levels, respectively, of gonadotropin-releasing hormone receptor(GnRH-R) in the pituitary tissue, follicle-stimulating hormone receptor(FSHR) and luteinizing hormone receptor(LHR) in the ovarian tissue, and estrogen receptor(ER) in the uterine tissue. The results showed that the writhing response, serum levels of PGF_(2α), GnRH, FSH, LH, and E_2, ovarian and uterine indexes, the protein and mRNA levels of GnRH-R in the pituitary tissue, FSHR and LHR in the ovarian tissue, and ER in the uterine tissue were significantly increased in the model group compared with those in the control group. GGD inhibited the writhing response, reduced the serum levels of PGF_(2α), GnRH, FSH, LH, and E_2, decreased the ovarian and uterine indexes, and down-regulated the protein and mRNA levels of GnRH-R in the pituitary tissue, FSHR and LHR in the ovarian tissue, and ER in the uterine tissue. The data suggested that GGD can regulate the HPOA and inhibit E_2 generation in the mice experiencing recurrent PD by down-regulating the expression of proteins and genes related to HPOA axis, thus exerting the therapeutic effect on PD.


Asunto(s)
Medicamentos Herbarios Chinos , Dismenorrea , Ovario , Animales , Femenino , Ratones , Ovario/efectos de los fármacos , Ovario/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Dismenorrea/tratamiento farmacológico , Dismenorrea/metabolismo , Dismenorrea/genética , Dismenorrea/fisiopatología , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Hipófisis/metabolismo , Hipófisis/efectos de los fármacos , Humanos , Receptores de HFE/genética , Receptores de HFE/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/genética , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Receptores LHRH/genética , Receptores LHRH/metabolismo , Receptores de HL/genética , Receptores de HL/metabolismo
2.
BMC Ophthalmol ; 22(1): 311, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-35850684

RESUMEN

BACKGROUND: To investigate the effects of vitamin C on central retinal thickness and choroidal thickness. METHODS: A total of 69 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 69 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT). RESULTS: The average retinal thickness was 269.07 ± 13.51 µm in the vitamin C deficiency group and 276.92 ± 13.51 µm in the control group. The average choroidal thickness was 195.62 ± 66.40 µm in the in the vitamin C deficiency group and 238.86 ± 55.08 µm in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p < 0.001, and = 0.001 respectively). CONCLUSION: The central retinal and choroidal thickness were thinner in vitamin C deficiency group compared with normal individuals. These findings suggested that vitamin C deficiency might play an important role in retinal and choroidal diseases.


Asunto(s)
Deficiencia de Ácido Ascórbico , Tomografía de Coherencia Óptica , Ácido Ascórbico , Deficiencia de Ácido Ascórbico/complicaciones , Coroides , Humanos , Retina , Tomografía de Coherencia Óptica/métodos
3.
J Am Chem Soc ; 143(43): 17920-17925, 2021 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-34677051

RESUMEN

Materials capable of degradation upon exposure to light hold promise in a diverse range of applications including biomedical devices and smart coatings. Despite the rapid access to macromolecules with diverse compositions and architectures enabled by ring-opening metathesis polymerization (ROMP), a general strategy to introduce facile photodegradability into these polymers is lacking. Here, we report copolymers synthesized via ROMP that can be degraded by cleaving the backbone in both solution and solid states under irradiation with a 52 W, 390 nm Kessil LED to generate heterotelechelic low-molecular-weight fragments. To the best of our knowledge, this work represents the first instance of the incorporation of acylsilanes into a polymer backbone. Mechanistic investigation of the degradation process supports the intermediacy of an α-siloxy carbene, formed via a 1,2-photo Brook rearrangement, which undergoes insertion into water followed by cleavage of the resulting hemiacetal.


Asunto(s)
Polímeros/química , Silanos/química , Fotólisis , Polimerizacion , Polímeros/síntesis química , Polímeros/efectos de la radiación , Silanos/síntesis química , Silanos/efectos de la radiación , Rayos Ultravioleta
4.
Magn Reson Med ; 85(5): 2709-2722, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33283943

RESUMEN

PURPOSE: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)-specific gas-phase (GP) depolarization maps using xenon-polarization transfer contrast (XTC) MR imaging. METHODS: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single-breath XTC data were acquired through a series of three GP images using a 2D multi-slice GRE during a 12 s breath-hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in-between the images to quantify the exchange between the GP and dissolved-phase (DP) compartments. Inversion pulses were either centered on-resonance to generate contrast, or off-resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off-resonance pulses. Finally, this technique was extended to a multi-breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions. RESULTS: Inversion pulses shifted off-resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches. CONCLUSION: The proposed DP-compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath-hold duration or the overall number of breath-holds open avenues for future research to improve measurement accuracy and patient comfort.


Asunto(s)
Intercambio Gaseoso Pulmonar , Isótopos de Xenón , Humanos , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Xenón
5.
J Fish Biol ; 99(5): 1708-1718, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34392536

RESUMEN

The ontogenesis of catabolic abilities and energy metabolism during endogenous nutritional periods of tongue sole was investigated. In this work, trypsin-like proteases (TRY) and triglyceride lipase (LIP) activities were measured to assess the capacities to catabolize proteins and lipids, respectively. Meanwhile, specific enzymes including pyruvate kinase (PK), glutamic oxalo acetic transaminase (GOT) and glutamate dehydrogenase (GDH), and hydroxyacyl CoA dehydrogenase (HOAD) as well as their ratios were assayed to evaluate the abilities to use energy substrates of carbohydrates, amino acids and fatty acids, respectively, for energy production. In addition, activities of citrate synthase (CS) and lactate dehydrogenase (LDH) and LDH/CS ratio were calculated to analyse the evolution of aerobic and anaerobic pathways. The study found that hatching occurred at 38.8 h after fertilization (HAF), mouth-opening day of eleuteroembryo appeared at 3 days after hatching (DAH), and the most rapid embryonic growth was observed in blastula stage before hatching. Enzymatic assay revealed that except for PK which appeared in cleavage stage onwards, all the other enzymes functioned after fertilization, preparing well for the coming embryogenesis of tongue sole. By comparing the average specific activity of enzyme in each period, it can be found that the highest value occurred at 3 DAH (for TRY, LIP, PK and LDH), 2 DAH (for GDH), fertilized egg (for GOT) and segmentation stage (for HOAD and CS), and the lowest value occurred at fertilized egg (for HOAD, CS and GDH), cleavage stage (for TRY, PK and LDH), gastrula stage (for GOT) and hatching day (for LIP). Based on the changeable patterns of metabolic enzymatic activities and ratios, it is concluded that metabolic capacities on three energy substrates displayed stage-specific traits, and the dominant energy substrate was fatty acids before segmentation stage, amino acids until hatching day and carbohydrate during eleuteroembryo period. As for energy production mode, aerobic pathway appeared to increase greater in fertilized egg and gastrula stage, whereas anaerobic pathway played a predominant role during cleavage stage, blastula stage, segmentation stage and eleuteroembryo stage. These results are valuable to elucidate the nutritional requirements of embryonic stages in tongue sole and to further understand their energy metabolic mechanisms.


Asunto(s)
Desarrollo Embrionario , Metabolismo Energético , Lenguado , Animales , Citrato (si)-Sintasa/metabolismo , Lenguado/metabolismo , L-Lactato Deshidrogenasa/metabolismo
6.
Magn Reson Med ; 84(6): 3027-3039, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32557808

RESUMEN

PURPOSE: To investigate biases in the measurement of apparent alveolar septal wall thickness (SWT) with hyperpolarized xenon-129 (HXe) as a function of acquisition parameters. METHODS: The HXe MRI scans with simultaneous gas-phase and dissolved-phase excitation were performed using 1-dimensional projection scans in mechanically ventilated rabbits. The dissolved-phase magnetization was periodically saturated, and the dissolved-phase xenon uptake dynamics were measured at end inspiration and end expiration with temporal resolutions up to 10 ms using a Look-Locker-type acquisition. The apparent alveolar septal wall thickness was extracted by fitting the signal to a theoretical model, and the findings were compared with those from the more commonly use chemical shift saturation recovery MRI spectroscopy technique with several different delay time arrangements. RESULTS: It was found that repeated application of RF saturation pulses in chemical shift saturation recovery acquisitions caused exchange-dependent gas-phase saturation that heavily biased the derived SWT value. When this bias was reduced by our proposed method, the SWT dependence on lung inflation disappeared due to an inherent insensitivity of HXe dissolved-phase MRI to thin alveolar structures with very short T2∗ . Furthermore, perfusion-based macroscopic gas transport processes were demonstrated to cause increasing apparent SWTs with TE (2.5 µm/ms at end expiration) and a lung periphery-to-center SWT gradient. CONCLUSION: The apparent SWT measured with HXe MRI was found to be heavily dependent on the acquisition parameters. A method is proposed that can minimize this measurement bias, add limited spatial resolution, and reduce measurement time to a degree that free-breathing studies are feasible.


Asunto(s)
Pulmón , Isótopos de Xenón , Animales , Sesgo , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Conejos
7.
BMC Infect Dis ; 20(1): 849, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33198648

RESUMEN

BACKGROUND: Mycobacterium houstonense is rapidly growing mycobacteria (RGM) that belongs to M. fortuitum group. So far, there have been few associated reports of human diseases induced by M. houstonense worldwide. CASE PRESENTATION: We present a delayed-onset postoperative endophthalmitis caused by M. houstonense after glaucoma drainage implant (GDI) surgery. The ocular infection lasted for 2 months without appropriate treatment that developed into endophthalmitis and the patient underwent an emergency enucleation. CONCLUSION: Implant erosion and a delay in diagnosis of ocular infection could lead to irreversible damage as observed in our case. Ophthalmologists should be alert for ocular RGM infection, and prompt laboratory diagnosis with initiation of effective multidrug therapy might prevent loss of vision.


Asunto(s)
Endoftalmitis/diagnóstico , Endoftalmitis/etiología , Implantes de Drenaje de Glaucoma/efectos adversos , Mycobacteriaceae/genética , Complicaciones Posoperatorias/diagnóstico , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/cirugía , Enucleación del Ojo , Estudios de Seguimiento , Humanos , Levofloxacino/uso terapéutico , Masculino , Persona de Mediana Edad , Mycobacteriaceae/aislamiento & purificación , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/cirugía , ARN Ribosómico 16S/genética , ARN Ribosómico 23S/genética , Resultado del Tratamiento
8.
BMC Ophthalmol ; 20(1): 262, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32615955

RESUMEN

BACKGROUND: Posterior scleritis is an uncommon vision-threatening disorder that is often recurrent and difficult to cure due to its complex etiology. In HIV patients, posterior scleritis may develop several months after significant rise in CD4+ T-lymphocyte, even after several years, which may be diagnosed as late-onset immune recovery scleritis. CASE PRESENTATION: Here we report a case of posterior scleritis in a HIV positive patient who presented with severe periocular pain and decreased vision in the left eye, with exudative retinal detachment and optic nerve involvement. CONCLUSIONS: Early differential diagnosis of immune recovery posterior scleritis and intensive corticosteroids treatment, can prevent vision loss effectively in HIV patients.


Asunto(s)
Infecciones por VIH , Desprendimiento de Retina , Escleritis , Corticoesteroides , Infecciones por VIH/complicaciones , Humanos , Escleritis/diagnóstico , Escleritis/tratamiento farmacológico , Escleritis/etiología , Trastornos de la Visión
9.
Int Ophthalmol ; 40(8): 2023-2029, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32342255

RESUMEN

PURPOSE: To evaluate the safety of phacoemulsification cataract surgery in the patients undergoing dual antiplatelet therapy with aspirin and clopidogrel. METHODS: Consecutive patients undergoing phacoemulsification cataract surgery with a clear corneal incision under topical anesthesia were eligible for inclusion in the study. Thirty-eight eyes from 38 patients on combined aspirin and clopidogrel therapy who continued the treatment were classified into the maintenance group, a matched group of 38 eyes from 38 patients on no antiplatelet/anticoagulant therapy as the control group. The best-corrected visual acuity (BCVA) and incidences of complications were compared between the two groups. RESULTS: There was no significant difference in final BCVA between the maintenance group and the control group (p = 0.178). No significant difference existed in the incidences of hemorrhagic or non-hemorrhagic complications between the two groups (p = 0.529 and p = 0.589, respectively). Moreover, no surgery was postponed or cancelled due to hemorrhagic complications in either group, and no cardiovascular events occurred during the follow-up. There was no case of anterior chamber hemorrhage, vitreous hemorrhage, or suprachoroidal hemorrhage. CONCLUSIONS: Our outcomes indicated that phacoemulsification cataract surgery using a clear corneal incision with topical anesthesia could be safely done without stopping dual antiplatelet therapy with aspirin and clopidogrel.


Asunto(s)
Catarata , Facoemulsificación , Aspirina/efectos adversos , Catarata/complicaciones , Clopidogrel , Humanos , Implantación de Lentes Intraoculares , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo , Agudeza Visual
11.
Drug Dev Ind Pharm ; 44(6): 969-981, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29313395

RESUMEN

The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10, and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation. The prepared formulations were further characterized by the droplet size, self-microemulsifying time, zeta potential, polydispersity index (PDI), and robustness to dilution. The in vitro release profile of cinacalcet-SMEDDS was determined in four different release medium and in fasted state and fed state of simulated gastrointestinal fluid. Cinaclcet-SMEDDS were implemented under fed and fasted state in dogs and product REGPARA® was used as a comparison to the prepared formulation in the pharmacokinetics. The result showed the components of SMEDDS, the amount of oil, the ratio of surfactant, and co-surfactant was optimized using solubility, pseudo-ternary phase diagram studies, and response surface methodology. In vitro drug release studies indicated that the cinacalcet-SMEDDS eliminated the effect of pH variability in release medium and variational gastroenteric environments with improved drug release performance. Pharmacokinetic studies revealed that the profiles of cinacalcet-SMEDDS were similar both in the fasted and fed state compared with commercial product, indicating the formulation significantly promoted the absorption, enhanced bioavailability and had no food effect essentially. It is concluded that poorly water-soluble drug cinacalcet was improved in the solubility and bioavailability by using a successful oral dosage form the SMEDDS, and eliminated food effect as well.


Asunto(s)
Cinacalcet/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Polietilenglicoles/química , Animales , Disponibilidad Biológica , Cinacalcet/química , Perros , Liberación de Fármacos , Solubilidad , Tensoactivos/química , Agua
12.
AAPS PharmSciTech ; 19(4): 1847-1859, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29637496

RESUMEN

In this paper, a novel self-nanoemulsifying drug delivery system (SNEDDS) was used to improve the oral bioavailability in fasted state and diminish the food effect for rivaroxaban. Oil, surfactant, and co-surfactant were selected by saturated solubility study. IPM, Tween80, and 1,2-propanediol were finally selected as oil, surfactant, and co-surfactant, respectively. The pseudo-ternary-phase diagram was utilized to optimize the preliminary composition of SNEDDS formulation. The optimized rivaroxaban-SNEDDS formulation was selected by central composite design (CCD) of response surface methodology. Optimized SNEDDS formulation was evaluated for drug content, self-emulsifying time, droplet size, zeta potential, polydispersity index, Fourier transform-infrared (FTIR) spectroscopy, and transmission electron microscope (TEM). The drug dissolution profile compared to the commercial formulation Xarelto® (20 mg rivaroxaban) was determined in four different media (pH 1.2HCl, pH 4.5NaAc-HAc, pH 6.8PBS, and water). The result indicated that the SNEDDS formulation had successfully increased the drug solubility in four different media. A HPLC-MS method that indicated a high sensitivity, strong attribute, and high accuracy characteristic was built to measure the drug concentration in plasma. The fast/fed in vivo pharmacokinetics studies of SNEDDS formulation and Xarelto® were carried out in adult beagle dog, rivaroxaban with no food effect was achieved in SNEDDS formulation compared with Xarelto® in fed state. The result suggested that SNEDDS formulation in this study is useful to increase the oral bioavailability and diminish the food effect in fasted state.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/administración & dosificación , Interacciones Alimento-Droga/fisiología , Nanopartículas/administración & dosificación , Rivaroxabán/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Perros , Liberación de Fármacos , Emulsionantes/síntesis química , Emulsiones , Ayuno/metabolismo , Femenino , Masculino , Nanopartículas/química , Nanopartículas/metabolismo , Tamaño de la Partícula , Rivaroxabán/síntesis química , Rivaroxabán/metabolismo , Solubilidad , Tensoactivos/administración & dosificación , Tensoactivos/síntesis química , Tensoactivos/metabolismo
13.
AAPS PharmSciTech ; 19(8): 3599-3608, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30238303

RESUMEN

To enhance the oral bioavailability and eliminate the food effect of probucol. Probucol-phospholipid complex was prepared using solvent-evaporation method in this research. Several methods were used to validate the formation of complexes, such as FT-IR, SEM, DSC and PXRD, and the solubility of PRO and PRO-PLC was detected by HPLC. Pharmacokinetic testing was conducted in the fasted and fed state. FTIR, SEM, DSC and PXRD validated the existence of PRO-PLC. The solubility of PRO in complexes was 15.05 µg/mL, which was 215-fold of the PRO-API. The dissolution rate was increased by preparing PRO-PLC. Compared with commercial tablets, the PRO-PLC complexes exhibited higher peak plasma concentration (1.69 ± 0.44 µg/mL), increased AUC0-24 h (6.8 ± 1.3 µg/mL h), which mean the bioavailability of PRO was increased. In addition, the absorption of PRO was not interfered with food. In conclusion, an improved solubility and bioavailability was achieved with the preparation of PRO-PLC. Additionally, the dissolution behaviour was good and the food effect was eliminated.


Asunto(s)
Fosfolípidos/química , Probucol/química , Animales , Disponibilidad Biológica , Perros , Interacciones Alimento-Droga , Fosfolípidos/farmacocinética , Probucol/farmacocinética , Solubilidad
14.
J Biol Chem ; 291(44): 22977-22987, 2016 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-27605665

RESUMEN

Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens.


Asunto(s)
Barrera Hematorretinal/metabolismo , Moléculas de Adhesión Celular/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Lectinas Tipo C/metabolismo , Receptores de Superficie Celular/metabolismo , Uniones Estrechas/metabolismo , Barrera Hematorretinal/virología , Moléculas de Adhesión Celular/genética , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Lectinas Tipo C/genética , Permeabilidad , Unión Proteica , Receptores de Superficie Celular/genética , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo , Uniones Estrechas/genética , Uniones Estrechas/virología
15.
Bioorg Chem ; 75: 217-223, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28987877

RESUMEN

The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50=2µM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function.


Asunto(s)
Emodina/química , Emodina/farmacología , Plasmodium falciparum/enzimología , Proteínas Quinasas/química , Proteínas Quinasas/farmacología , Proteínas Protozoarias/antagonistas & inhibidores , Secuencia de Aminoácidos , Antraquinonas/química , Emodina/metabolismo , Activación Enzimática/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/parasitología , Humanos , Concentración 50 Inhibidora , Microscopía Fluorescente , Plasmodium falciparum/efectos de los fármacos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/metabolismo
16.
Med Sci Monit ; 23: 3345-3352, 2017 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-28692639

RESUMEN

BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 µm) between the tamponades. However, in the severe group (foveoschisis height >400 µm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 µm, but C3F8 is more effective for patients with a foveoschisis height >400 µm.


Asunto(s)
Fluorocarburos/uso terapéutico , Retinosquisis/cirugía , Vitrectomía/métodos , Anciano , Aire , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía/cirugía , Miopía/terapia , Retina/fisiología , Estudios Retrospectivos , Agudeza Visual
17.
Heliyon ; 10(7): e29107, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38623223

RESUMEN

Background: To investigate the associations between retinal/choroidal microvasculature and carotid plaque in patients with CAD assessed by optical coherence tomography angiography (OCTA). Methods: This study included 127 CAD patients with and 79 without carotid plaque. Each patient had both OCTA taken and digitized to determine retinal/choroidal thickness, vessel density and flow area and carotid ultrasound for carotid plaque size and stability measurement. The superficial capillary plexus (SCP), deep capillary plexus (DCP), out retina and choriocapillaris vessel density, out retina and choriocapillaris flow area, and full retina thickness were analyzed in the fovea centered 6 × 6 mm area. The association between OCTA measurements and carotid plaque characteristics in patients with CAD were evaluated. Results: The duration of hypertension and diabetes mellitus (DM) was significantly longer in CAD patients with carotid plaque than that without (p < 0.001). The mean values for vessel density SCP and DCP (except fovea zone), and choriocapillaris nasal zone were significantly lower in plaque group (p < 0.05). Negative correlations between the carotid plaque width and vessel density SCP and DCP (except fovea zone) (p < 0.05) were also found in this study. Conclusions: In patients with CAD, carotid plaque, a risk factor and marker of atherosclerosis and stenosis, is significantly and independently associated with retinal and choroidal microvascular changes by OCTA.

18.
J Acquir Immune Defic Syndr ; 96(3): 299-303, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38534141

RESUMEN

OBJECTIVE: Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies. DESIGN: Observational, retrospective study. METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042). CONCLUSIONS: The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.


Asunto(s)
Alquinos , Fármacos Anti-VIH , Benzoxazinas , Ciclopropanos , Infecciones por VIH , VIH-1 , Carga Viral , Humanos , Benzoxazinas/uso terapéutico , Benzoxazinas/farmacocinética , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/virología , ARN Viral/sangre , Vitrectomía
19.
Heliyon ; 10(8): e29305, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655359

RESUMEN

Background: To investigate the correlation between retinal vessel density (VD) parameters with serum B-type natriuretic peptide (BNP) in patients with coronary heart disease (CHD) using novel optical coherence tomography angiography (OCTA) denoising images based on artificial intelligence (AI). Methods: OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device in 176 patients with CHD. Baseline information and blood test results were recorded. Results: Retinal VD parameters of the macular and optic nerves on OCTA were significantly decreased in patients with CHD after denoising. Retinal VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC) was strongly correlated with serum BNP levels in patients with CHD. Significant differences were noted in retinal thickness and retinal VD (SCP, DCP and RPC) between the increased BNP and normal BNP groups in patients with CHD. Conclusion: Deep learning denoising can remove background noise and smooth rough vessel surfaces. SCP,DCP and RPC may be potential clinical markers of cardiac function in patients with CHD. Denoising shows great potential for improving the sensitivity of OCTA images as a biomarker for CHD progression.

20.
Indian J Ophthalmol ; 72(Suppl 2): S327-S330, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38271432

RESUMEN

To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.


Asunto(s)
Hendiduras de Ciclodiálisis , Lesiones Oculares , Humanos , Hendiduras de Ciclodiálisis/cirugía , Lesiones Oculares/diagnóstico , Lesiones Oculares/cirugía , Lesiones Oculares/complicaciones , Presión Intraocular , Tonometría Ocular , Cuerpo Ciliar/cirugía , Suturas
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