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1.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(3): 342-347, 2024 Mar 15.
Artículo en Chino | MEDLINE | ID: mdl-38500429

RESUMEN

Objective: To analyze the clinical characteristics of scar cancer ulcer wound of head and face, and to investigate its diagnosis and treatment. Methods: The clinical data of 14 patients with head and facial scar cancer ulcer wounds who met the selection criteria and admitted between January 2021 and March 2022 were retrospectively analyzed. There were 8 males and 6 females. The age of onset ranged from 21 to 81 years with an average age of 61.6 years. The incubation period ranged from 1 month to 70 years, with a median of 4 years. Site of the disease included 7 cases of head, 6 cases of maxillofacial region, and 1 case of neck region. Injury factors included trauma in 5 cases, scratch in 5 cases, scalding in 2 cases, burn in 1 case, and needle puncture in 1 case. Pathological results showed squamous cell carcinoma in 9 cases, basal cell carcinoma in 3 cases, sebaceous adenocarcinoma in 1 case, papillary sweat duct cystadenoma combined with tubular apocrine sweat gland adenoma in 1 case. There was 1 case of simple extensive tumor resection, 1 case of extensive tumor resection and skin grafting repair, 7 cases of extensive tumor resection and local flap repair, and 5 cases of extensive tumor resection and free flap repair. Results: All the 14 patients were followed up 16-33 months (mean, 27.8 months). Two patients (14.29%) had scar cancer ulcer wound recurrence, of which 1 patient recurred at 2 years after 2 courses of postoperative chemotherapy, and was still alive after oral traditional Chinese medicine treatment. One patient relapsed at 1 year after operation and died after 2 courses of chemotherapy. One patient underwent extensive resection of the left eye and periocular tumor and the transfer and repair of the chimaeric muscle axial flap with the perforating branch of the descending branch of the left lateral circumflex femoral artery, but the incision healing was poor after operation, and healed well after anti-infection and debridement suture. The wounds of other patients with scar cancer ulcer did not recur, and the wounds healed well. Conclusion: Scar cancer ulcer wound of the head and face is common in the middle-aged and elderly male, and the main pathological type is squamous cell carcinoma. Local extensive resection, skin grafting, or flap transfer repair are the main treatment methods. Early active treatment of wounds after various injuries to avoid scar repeated rupture and infection is the foundamental prevention of scar cancer.


Asunto(s)
Quemaduras , Carcinoma de Células Escamosas , Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Neoplasias Cutáneas , Traumatismos de los Tejidos Blandos , Persona de Mediana Edad , Anciano , Femenino , Humanos , Masculino , Adulto Joven , Adulto , Anciano de 80 o más Años , Cicatriz/terapia , Cicatriz/cirugía , Úlcera/cirugía , Estudios Retrospectivos , Trasplante de Piel , Carcinoma de Células Escamosas/cirugía , Quemaduras/complicaciones , Quemaduras/terapia , Traumatismos de los Tejidos Blandos/cirugía , Neoplasias Cutáneas/cirugía , Resultado del Tratamiento , Colgajo Perforante/trasplante
2.
Med Phys ; 51(1): 601-611, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37831515

RESUMEN

BACKGROUND: While the development of CT imaging technique has brought cognition of in vivo organs, the resolution of CT images and their static characteristics have gradually become barriers of microscopic tissue research. PURPOSE: Previous research used the finite element method to study the airflow and gas exchange in the alveolus and acinar to show the fate of inhaled aerosols and studied the diffusive, convective, and sedimentation mechanisms. Our study combines these techniques with CT scan simulation to study the mechanisms of respiratory movement and its imaging appearance. METHODS: We use 3D fluid-structure interaction simulation to study the movement of an ideal alveolus under regular and forced breathing situations and ill alveoli with different tissue elasticities. Additionally, we use the Monte Carlo algorithm within the OpenGATE platform to simulate the computational CT images of the dynamic process with different designated resolutions. The resolutions show the relationship between the kinematic model of the human alveolus and its imaging appearance. RESULTS: The results show that the alveolus and the wall thickness can be seen with an image resolution smaller than 15.6 µm. With ordinary CT resolution, the alveolus is expressed with four voxels. CONCLUSIONS: This is a preliminary study concerning the imaging appearance of the dynamic alveolus model. This technique will be used to study the imaging appearance of the dynamic bronchial tree and the lung lobe models in the future.


Asunto(s)
Pulmón , Alveolos Pulmonares , Humanos , Pulmón/diagnóstico por imagen , Alveolos Pulmonares/diagnóstico por imagen , Respiración , Aerosoles , Tomografía Computarizada por Rayos X , Simulación por Computador
3.
Ann Plast Surg ; 91(6): 763-770, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37962184

RESUMEN

ABSTRACT: The purpose of this study was to introduce a modified suture technique and to compare its effects on skin scar formation with 2 traditional suture methods: simple interrupted suture (SIS) and vertical mattress suture (VMS). Three groups of healthy adult female Sprague-Dawley rats were selected (6 replicates in each group), and the full-thickness skin of 5 cm × 0.2 cm was cut off on the back of the rats after anesthesia. The wounds were then sutured using 1 of the 3 methods for each group: SIS, VMS, and a newly introduced modified vertical mattress suture (M-VMS) technique with the needle reinsertion at the exit point. A traction device was installed on the back of the rats to achieve high tension wounds. The tensile distance was increased by 1 mm every day for 20 days. After 20 days of healing, the hematoxylin-eosin staining method was used for observation of scar morphology. The collagen production rate was measured by Masson staining, and the type I collagen and type III collagen were detected by the immunofluorescence method. Immunohistochemical staining was used to detect the expression of myofibroblast marker α-smooth muscle actin, and real-time quantitative polymerase chain reaction and Western blot techniques were used to detect the expressions of transforming growth factors TGFß1, TGFß2, and TGFß3 to understand the mechanisms of scar formation. Results showed that the quantity and density of collagen fibers were both lower in the M-VMS group than in the other 2 groups. Immunofluorescence results showed that type I collagen was significantly lower, whereas type III collagen was significantly higher in the M-VMS group than in the other 2 groups. The expressions of α-smooth muscle actin and TGFß1 both were lower in the M-VMS group than in the other 2 groups. The expression of TGFß2 and TGFß3 had no obvious difference among the 3 groups. For wounds under high tension, compared with SIS and VMS methods, the M-VMS technique we proposed can reduce scar formation due to the reduction of collagen formation, myofibroblast expression, and TGFß1 expression.


Asunto(s)
Cicatriz , Colágeno Tipo I , Ratas , Femenino , Animales , Cicatriz/prevención & control , Colágeno Tipo III , Actinas , Ratas Sprague-Dawley , Colágeno , Técnicas de Sutura
4.
Sci Rep ; 13(1): 19199, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932335

RESUMEN

CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.


Asunto(s)
Acinetobacter baumannii , Artículos Domésticos , Osteopatía , Sistemas CRISPR-Cas , Pseudomonas aeruginosa
5.
Front Cell Infect Microbiol ; 13: 1223696, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37662004

RESUMEN

Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens in nosocomial infections, and a considerable number of their clinical isolates are not susceptible to conventional antimicrobial therapy. Therefore, innovative therapeutic strategies that can effectively deal with ESKAPE pathogens will bring huge social and economic benefits and ease the suffering of tens of thousands of patients. Among these strategies, CRISPR (clustered regularly interspaced short palindromic repeats) system has received extra attention due to its high specificity. Regrettably, there is currently no direct CRISPR-system-based anti-infective treatment. This paper reviews the applications of CRISPR-Cas system in the study of ESKAPE pathogens, aiming to provide directions for the research of ideal new drugs and provide a reference for solving a series of problems caused by multidrug-resistant bacteria (MDR) in the post-antibiotic era. However, most research is still far from clinical application.


Asunto(s)
Acinetobacter baumannii , Infección Hospitalaria , Enterococcus faecium , Humanos , Sistemas CRISPR-Cas , Acinetobacter baumannii/genética , Antibacterianos/uso terapéutico , Infección Hospitalaria/diagnóstico
6.
Adv Healthc Mater ; 12(24): e2203400, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37462927

RESUMEN

Tendon injuries range from acute-related trauma to chronic-related injuries are prevalent and bring substantial pain, functional loss, and even disability to the patients. The management of tendon injuries is tricky due to the innate limited regenerative capability of the tendon. Currently, surgical intervention of tendon injuries with artificial tendons remains the standard of care. However, most of artificial tendons are manufactured with synthetic materials, which possess relatively poor biomimetic characteristics and inadequate inherent biodegradability, hence rendering limited cell proliferation and migration for tendon healing. To address these limitations, this work develops a mussel-derived artificial tendon based on double-cross-linked chitosan modification. In this design, decellularized artificial tendon serves as a natural biomimetic scaffold to facilitate the migration and adhesion of tendon repair cells. Additionally, as the cells proliferate, the artificial tendon can be degraded to facilitate tendon regeneration. Moreover, the chitosan cross-linking further enhances the mechanical strength of artificial tendon and offers a controllable degradation. The in vitro and in vivo experimental results demonstrate that mussel-derived artificial tendon not only accelerate the tendon functional reconstruction but also enable harmless clearance at postimplantation. The finding provides a promising alternative to conventional artificial tendons and spurs a new frontier to explore nature-derived artificial tendons.


Asunto(s)
Quitosano , Traumatismos de los Tendones , Humanos , Andamios del Tejido , Tendones/metabolismo , Traumatismos de los Tendones/terapia , Traumatismos de los Tendones/metabolismo , Proliferación Celular
7.
Curr Microbiol ; 80(6): 199, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37120784

RESUMEN

Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen associated with serious clinical challenges owing to its rapidly increasing resistance to antibiotics. Due to their high host specificity and easy access to the natural environment, bacteriophages (phages) may serve as good antibacterial agents. Phage therapy has been successfully used to treat antibiotic-resistant A. baumannii infections. As a fundamental step before phage therapy, the characterization and sequencing of A. baumannii phages have been well studied. Until October 2022, 132 A. baumannii phages have been sequenced and studied, with their genomes ranging from 4 to 234 kb, and we summarize the characterized and sequenced A. baumannii phages. This review is a current and short overview that does not go into detail on the A. baumannii phages. In addition, preclinical studies and clinical applications of A. baumannii phages are also included.


Asunto(s)
Acinetobacter baumannii , Bacteriófagos , Bacteriófagos/genética , Acinetobacter baumannii/genética , Antibacterianos , Secuencia de Bases
8.
Hum Vaccin Immunother ; 19(1): 2175519, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-36935353

RESUMEN

The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies, phage therapy (PT) is promising. This review extensively summarizes preclinical PT approaches in various in-vivo models. PT has been evaluated in several recent clinical trials. However, there are still several unanswered concerns due to a lack of appropriate regulation and pharmacokinetic data regarding the application of phages in human therapeutic procedures. In this review, we also presented the current state of PT and considered how animal models can be used to adapt these therapies for humans. The development of realistic solutions to circumvent these constraints is critical for advancing this technology.


Asunto(s)
Infecciones Bacterianas , Bacteriófagos , Terapia de Fagos , Animales , Humanos , Terapia de Fagos/métodos , Infecciones Bacterianas/tratamiento farmacológico , Bacteriófagos/fisiología , Farmacorresistencia Bacteriana Múltiple , Modelos Animales , Antibacterianos/uso terapéutico
9.
Int Wound J ; 20(6): 2169-2180, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36740974

RESUMEN

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long-lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA-seq identified 437 differentially regulated genes after an 8-h compression intervention compared with control cells, among which 256 genes were up-regulated and 181 genes were down-regulated. Further q-PCR analysis confirmed that early growth response 1(EGR1) and c-fos were down-regulated after an 8-h compression intervention. However, the down-regulation of EGR1 and c-fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20-h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor ß1(TGF-ß1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α-SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.


Asunto(s)
Colágeno Tipo I , Hidrogeles , Humanos , Hidrogeles/uso terapéutico , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Fibroblastos/metabolismo , Fibrosis , Metaloproteasas/metabolismo , Metaloproteasas/farmacología , Actinas/metabolismo
10.
Sci Rep ; 13(1): 188, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36604462

RESUMEN

Acinetobacter baumannii has become one of the most challenging conditional pathogens in health facilities. It causes various infectious diseases in humans, such as wound or urinary tract infections and pneumonia. Phage therapy has been used as an alternative strategy for antibiotic-resistant A. baumannii infections and has been approved by several governments. Previously, we have reported two potential phage therapy candidates, Abp1 and Abp9, both of which are narrow-host-range phages. In the present study, we screened and isolated 22 A. baumannii bacteriophages from hospital sewage water and determined that Abp95 has a wide host range (29%; 58/200). The biological and genomic characteristics and anti-infection potential of Abp95 were also investigated. Abp95 belongs to the Myoviridae family, with a G+C content of 37.85% and a genome size of 43,176 bp. Its genome encodes 77 putative genes, none of which are virulence, lysogeny, or antibiotic resistance genes. Abp95 was found to accelerate wound healing in a diabetic mouse wound infection model by clearing local infections of multidrug-resistant A. baumannii. In conclusion, the lytic phage Abp95, which has a wide host range, demonstrates potential as a candidate for phage therapy against multiple sequence types of carbapenem-resistant A. baumannii.


Asunto(s)
Acinetobacter baumannii , Bacteriófagos , Animales , Ratones , Humanos , Bacteriófagos/genética , Acinetobacter baumannii/genética , Genoma Viral , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Genotipo , Farmacorresistencia Bacteriana Múltiple/genética
11.
Infect Drug Resist ; 15: 7577-7599, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36579125

RESUMEN

Purpose: Pseudomonas aeruginosa is a common pathogen of infection in burn and trauma patients, and multi-drug resistant P. aeruginosa has become an increasingly important pathogen. Essential genes are key to the development of novel antibiotics. The PA0715 gene is a novel unidentified essential gene that has attracted our interest as a potential antibiotic target. Our study aims to determine the exact role of PA0715 in cell physiology and bacterial pathogenicity, providing important clues for antibiotic development. Patients and Methods: The shuttle vector pHERD20T containing an arabinose inducible promoter was used to construct the CRISPRi system. Alterations in cellular physiology and bacterial pathogenicity of P. aeruginosa PAO1 after PA0715 inhibition were characterized. High-throughput RNA-seq was performed to gain more insight into the mechanisms by which PA0715 regulates the vital activity of P. aeruginosa. Results: We found that down-regulation of PA0715 significantly reduced PAO1 growth rate, motility and chemotaxis, antibiotic resistance, pyocyanin and biofilm production. In addition, PA0715 inhibition reduced the pathogenicity of PAO1 to the greater galleria mellonella larvae. Transcriptional profiling identified 1757 genes including those related to amino acid, carbohydrate, ketone body and organic salt metabolism, whose expression was directly or indirectly controlled by PA0715. Unexpectedly, genes involved in oxidative phosphorylation also varied with PA0715 levels, and these findings support a hitherto unrecognized critical role for PA0715 in oxidative respiration in P. aeruginosa. Conclusion: We identified PA0715 as a global regulator of the metabolic network that is indispensable for the survival and reproduction of P. aeruginosa. Our results provide a basis for future studies of potential antibiotic targets for P. aeruginosa and offer new ideas for P. aeruginosa infection control.

12.
Biotechnol Bioeng ; 119(10): 2731-2742, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35859248

RESUMEN

With the increasingly serious drug resistance of Acinetobacter baumannii, there is an increasingly urgent need for new antibacterial drugs. Phage lysin PlyAB1 has a bactericidal effect on drug-resistant A. baumannii, which has the potential to replace antibiotics to fight infection caused by A. baumannii. However, its application is limited by its thermal stability and lytic activity. To solve these problems, molecular dynamics (MD) simulations combined with Hotspot wizard 3.0 were used to identify key residue sites affecting thermal stability, and evolutionary analysis combined with multiple sequence alignment was used to identify key residue sites affecting lytic activity. Four single-point variants with significantly increased thermal stability and four single-point variants with significantly lytic activity were obtained, respectively. Furthermore, by superimposing mutations, we obtained three double-point variants, G100Q/K69R, G100R/K69R, and G100K/K69R, with significantly improved thermal stability and improved lytic activity. At 45°C, the lytic activity and half-life of the optimal variant G100Q/K69R were 1.51- and 24-fold higher than those of the wild PlyAB1, respectively. These results deepen our understanding of the structure and function of phage lysin and contribute to the application of phage lysin in antibiotic substitution.


Asunto(s)
Acinetobacter baumannii , Bacteriófagos , Antibacterianos/farmacología , Bacteriófagos/genética , Mucoproteínas/farmacología
13.
Int J Med Sci ; 19(5): 952-964, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35693752

RESUMEN

Preventing fibrosis or hypertrophic scar formation following tissue damage is still a big challenge despite the numerous approaches clinicians currently use. Hitherto, no written account was available of a successful case of scarless skin healing after a severe burn injury. Here, we report the first case of the "perfect regenerative healing" of a severe burn wound with no hypertrophic scar formation in which a postage stamp skin autograft was covered with human cytotoxic-T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) gene-transferred pig skin. We also discuss the mechanisms involved in the scarless healing of human burn wounds.


Asunto(s)
Quemaduras , Trasplante de Piel , Animales , Quemaduras/genética , Quemaduras/cirugía , Cicatriz/genética , Cicatriz/patología , Humanos , Inmunoglobulinas , Piel/patología , Porcinos , Cicatrización de Heridas/genética
14.
Front Surg ; 9: 815125, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36684201

RESUMEN

A 36-year-old healthy male patient was presented to the emergency room 3 h after experiencing a laceration to the left foot caused by a porcelain shard. The defect measured 7.5 × 6.0 × 0.8 cm, and the composite amputated tissue consisted of skin and subcutaneous layers. The terminal branch of the lateral calcaneal artery was first anastomosed end-to-end to the corresponding artery in the wound defect. The lateral calcaneal nerve was anastomosed after blood flow was restored. The two lateral veins were anastomosed end-to-end to the corresponding veins in the wound defect. Postoperatively, 1.0 × 1.5 cm area of skin necrosis was present at the distal end of the tissue, which healed smoothly after two weeks of dressing changes. The patient had retained excellent aesthetic and functionality by the 37 month follow up. Although such isolated amputation is relatively rare, microsurgical replantation is, thus, a feasible option in the management of heel amputation.

15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1182-1185, 2021 Sep 15.
Artículo en Chino | MEDLINE | ID: mdl-34523286

RESUMEN

OBJECTIVE: To explore the feasibility and effectiveness of free transplantation of medial plantar Flow-through venous flap for primary repairing children's finger wounds with digital artery defect. METHODS: Between July 2016 and October 2020, 9 children who suffered finger wounds with digital artery defect were primary repaired with free transplantation of medial plantar Flow-through venous flap. There were 6 boys and 3 girls, with an average age of 6.8 years (range, 4-13 years). The defects were caused by heavy weight puncture injury in 5 cases and strangulation injury in 4 cases. Among them, there were 3 cases of index finger wounds, 3 cases of middle finger wounds, 2 cases of ring finger wounds, and 1 case of little finger wounds. The wound area ranged from 1.8 cm×1.5 cm to 4.0 cm×2.5 cm. The time from injury to operation was 1.3-8.6 hours, with an average of 4.8 hours. The flap area ranged from 2.0 cm×1.6 cm to 4.2 cm×2.6 cm. After the flaps were inverted, the veins were used to bridge the finger arteries while repairing the wounds. The donor site of the foot was sutured directly in 4 cases, and repaired with full-thickness skin grafts in 5 cases. RESULTS: All flaps survived, and hand wounds healed by first intention; 8 cases of foot donor site wounds healed by first intention, and 1 case had partial necrosis in the marginal area of the skin graft, which healed after dressing change. All 9 children were followed up 3-24 months, with an average of 9 months. The color and texture of the flap were similar to those of the surrounding normal skin, and the protective feeling was restored. The two-point discrimination of the flap was 7-10 mm, with an average of 8 mm. At last follow-up, according to the upper limb function evaluation standard of Hand Surgery Society of Chinese Medical Association, the finger function was excellent in 5 cases and good in 4 cases. There was no ulcer formation and scar hyperplasia in the foot donor site, which did not affect walking. CONCLUSION: The free transplantation of medial plantar Flow-through venous flap is an ideal repair method for repairing children's finger wounds with digital artery defect. It has the advantages of simple flap extraction, thin flap, similar color and texture to the skin of the hand, and concealed donor site.


Asunto(s)
Traumatismos de los Dedos , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Adolescente , Niño , Preescolar , Femenino , Traumatismos de los Dedos/cirugía , Humanos , Masculino , Trasplante de Piel , Traumatismos de los Tejidos Blandos/cirugía , Resultado del Tratamiento , Arteria Cubital
16.
J Med Chem ; 64(11): 7275-7295, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-33881312

RESUMEN

Pathogenic bacteria demonstrate incredible abilities to evade conventional antibiotics through the development of resistance and formation of dormant, surface-attached biofilms. Therefore, agents that target and eradicate planktonic and biofilm bacteria are of significant interest. We explored a new series of halogenated phenazines (HP) through the use of N-aryl-2-nitrosoaniline synthetic intermediates that enabled functionalization of the 3-position of this scaffold. Several HPs demonstrated potent antibacterial and biofilm-killing activities (e.g., HP 29, against methicillin-resistant Staphylococcus aureus: MIC = 0.075 µM; MBEC = 2.35 µM), and transcriptional analysis revealed that HPs 3, 28, and 29 induce rapid iron starvation in MRSA biofilms. Several HPs demonstrated excellent activities against Mycobacterium tuberculosis (HP 34, MIC = 0.80 µM against CDC1551). This work established new SAR insights, and HP 29 demonstrated efficacy in dorsal wound infection models in mice. Encouraged by these findings, we believe that HPs could lead to significant advances in the treatment of challenging infections.


Asunto(s)
Compuestos de Anilina/química , Antibacterianos/síntesis química , Fenazinas/química , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Diseño de Fármacos , Femenino , Halogenación , Humanos , Hierro/química , Deficiencias de Hierro , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Ratones , Ratones Endogámicos BALB C , Mycobacterium tuberculosis/efectos de los fármacos , Fenazinas/farmacología , Fenazinas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Relación Estructura-Actividad , Cicatrización de Heridas/efectos de los fármacos
17.
18.
Front Microbiol ; 11: 506068, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33013774

RESUMEN

Acinetobacter baumannii (A. baumannii) has emerged as one of the most troublesome pathogens in health care institutions. A. baumannii can cause a wide range of diseases in humans, including pneumonia and septicemia. Phage therapy has drawn great interest from medical researchers as a potential way to control infections by antibiotic-resistant A. baumannii. Using a pandrug-resistant clinical A. baumannii isolate ABZY9 as an indicator, we isolated a lytic phage Abp9 from hospital sewage. Abp9 belongs to myoviridae family and shows a wider host range of 12%. Abp9 contains a linear double-stranded DNA genome of 44,820 bp with a G + C content of 37.69%. The Abp9 genome contains 80 open reading frames, but lacks any known virulence genes or lysogen-formation genes. In a systemic A. baumannii infection mouse models, Abp9 treatment showed good therapeutic effects. We have also observed an excellent lytic activity against A. baumannii in biofilm form of growth in vitro. All of these suggest that Abp9 is a good candidate for the phage therapy against drug-resistant A. baumannii infections.

19.
Burns Trauma ; 8: tkaa026, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32905076

RESUMEN

BACKGROUND: Acinetobacter baumannii (A. baumannii) is one of the pivotal pathogens responsible for nosocomial infections, especially in patients with low immune response, and infection with carbapenem-resistant A. baumannii has been increasing in recent years. Rapid and accurate detection of carbapenem-resistance genes in A. baumannii could be of immense help to clinical staff. METHODS: In this study, a 15-µL reaction system for recombinase polymerase amplification (RPA) was developed and tested. We collected 30 clinical isolates of A. baumannii from the Burn Institute of Southwest Hospital of Third Military Medical University (Army Medical University) for 6 months and tested antibiotic susceptibility using the VITEK 2 system. A. baumannii was detected based on the bla OXA-51 gene by PCR, qPCR and 15 µL-RPA, respectively. Sensitivity and specificity were evaluated. In addition, PCR and 15 µL-RPA data for detecting the carbapenem-resistance gene bla OXA-23 were comparatively assessed. RESULTS: The detection limit of the bla OXA-51 gene by 15 µL RPA was 2.86 CFU/ml, with sensitivity comparable to PCR and qPCR. No positive amplification signals were detected in non-Acinetobacter isolates, indicating high specificity. However, only 18 minutes were needed for the 15 µL RPA assay. Furthermore, an antibiotic susceptibility test showed that up to 90% of A. baumannii strains were resistant to meropenem and imipenem; 15 µL RPA data for detecting bla OXA-23 showed that only 10% (n = 3) of A. baumannii isolates did not show positive amplification signals, and the other 90% of (n = 27) isolates were positive, corroborating PCR results. CONCLUSION: We demonstrated that the new 15 µL RPA assay for detecting bla OXA-23 in A. baumannii is faster and simpler than qPCR and PCR. It is a promising alternative molecular diagnostic tool for rapid and effective detection of A. baumannii and drug-resistance genes in the field and point-of-care testing.

20.
Disaster Med Public Health Prep ; 14(6): 769-775, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32367793

RESUMEN

OBJECTIVE: To explore the epidemiological characteristics of COVID-19 associated with SARS-Cov-2 in Guizhou province, and to compare the differences in epidemiology with other provinces. METHODS: The data were extracted from National Health Commission of the People's Republic of China, Health Commission of Guizhou province, and Health Commission of Hubei province from January 20 to February 12, 2020. Information included such as general demographic indicators, population data and clinical outcome. RESULTS: A total of 135 cases were analyzed in the study. The average age was 39.46±18.95 years. The ratio of males to females was 0.985:1. Most of COVID-19 patients were 18-45 years old (52.27%). Close contact history was the most common (37.88%), followed by residence history in Hubei (34.85%). There was no difference between males and females in age (P=0.953) and exposure condition (P=0.186). Correlation analysis showed that there was a significant positive correlation between the migration index and the number of confirmed cases (r=0.816, P=0.007). CONCLUSION: Among the cases, most patients were young adults. Most epidemiological characteristics were no difference between males and females. Family-based transmission should not be ignored, as a close contact history was the top reason of exposure. Moreover, population movements also had significant impact on outbreaks.


Asunto(s)
COVID-19/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , COVID-19/transmisión , China/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Distribución por Sexo , Adulto Joven
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