Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor

Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1% HGF or PBS thrice daily for 5 days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.

Preservação em próteses implantossuportadas: peri-implantite / reservation in implant-supported prostheses: Peri-implantitis

Resumo: A identificação e o tratamento da infecção ao redor do implante é uma etapa essencial na manutenção do implante osseointegrativo e isso reflete na vida útil da reabilitação. O principal objetivo do tratamento da peri-implantite é a utilização de métodos de descontaminação mecânica e química para eliminar a carga bacteriana na superfície do implante. O biofilme pode ser removido por métodos não cirúrgicos ou cirúrgicos. Nos casos mais graves, geralmente é necessário tratamento cirúrgico, cujo objetivo é corrigir o defeito ósseo existente, combinado com a aplicação do enxerto, para regenerar o tecido ósseo perdido no processo inflamatório. O propósito deste estudo é realizar uma revisão de literatura tendo como o tema preservação em próteses implantossuportadas: peri-implantite, a fim de guiar a conservação das reabilitações orais. Além de buscar maiores informações acerca do desenvolvimento da doença peri-implantar, bem como sua ligação com a doença periodontal e os fatores que contribuem para seu desenvolvimento. Para tanto, foram utilizados descritores como: “peri-implantite", "manutenção de implantes" e “ossointegração” nas bases de dados: Pubmed, Scielo, google acadêmico e Lilacs. Para possibilitar um melhor resultado, foram organizados tópicos para uma discussão final, sendo eles: conceito, etiologia, diagnóstico e tratamento. Foram encontradas dificuldades na manutenção dos implantes e a necessidade de se descrever o melhor planejamento para uma melhoria nos protocolos clínicos de preservação a fim de obter-se excelência nos desfechos clínicos.Abstract: The identification and treatment of infection around the implant is an essential step in the maintenance of the osseointegrative implant and this reflects on the lifetime of the rehabilitation. The main objective of peri-implantitis treatment is the use of mechanical and chemical decontamination methods to eliminate the bacterial load on the implant surface. Biofilm can be removed by non-surgical or surgical methods. In more severe cases, surgical treatment is usually necessary, the aim of which is to correct the existing bone defect, combined with the application of a graft, to regenerate the bone tissue lost in the inflammatory process. The purpose of this study is to conduct a literature review with the theme of preservation in implant-supported prostheses: peri-implantitis, in order to guide the conservation of oral rehabilitations. In addition to seeking more information about the development of peri-implant disease, as well as its connection with periodontal disease and the factors that contribute to its development. For this purpose, descriptors such as: “peri-implantitis”, “implant maintenance” and “bone integration” were used in the following databases: Pubmed, Scielo, academic Google and Lilacs. final discussion, namely: concept, etiology, diagnosis, and treatment. Difficulties were found in the maintenance of implants and the need to describe the best planning for an improvement in clinical preservation protocols in order to obtain excellence in clinical outcomes. Plaque control maintains the health of the soft tissue-implant interface.Keywords: Dental implants; Peri-implantitis; Bacterial plaque.

Treatment of infection-induced vascular pathologies is protective against persistent rough morphotype Mycobacterium abscessus infection in zebrafish

Mycobacterium abscessus infections are of increasing global prevalence and are often difficult to treat due to complex antibiotic resistance profiles. While there are similarities between the pathogenesis of M. abscessus and tuberculous mycobacteria, including granuloma formation and stromal remodeling, there are distinct molecular differences at the host-pathogen interface. Here we have used a zebrafish-M. abscessus model and host-directed therapies that were previously identified in the zebrafish-M. marinum model to identify potential host-directed therapies against M. abscessus infection. We find efficacy of anti-angiogenic and vascular normalizing therapies against rough M. abscessus infection, but no effect of anti-platelet drugs.

First Detection in West Africa of a Mutation That May Contribute to Artemisinin Resistance Plasmodium falciparum

Background: The spread of drug resistance has seriously impacted the effective treatment of infection with the malaria parasite, Plasmodium falciparum. Continuous monitoring of molecular marker polymorphisms associated with drug resistance in parasites is essential for malaria control and elimination efforts. Our study describes mutations observed in the resistance genes Pfkelch13, Pfcrt, and Pfmdr1 in imported malaria and identifies additional potential drug resistance-associated molecular markers.Methods: Chinese patients infected in Africa with P. falciparum were treated with intravenous (IV) injections of artesunate 240–360 mg for 3–5 days while hospitalized and treated with oral dihydroartemisinin-piperaquine (DHP) for 3 days after hospital discharge. Blood samples were collected and PCR sequencing performed on genes Pfkelch13, Pfcrt, and Pfmdr1 from all isolates.Results: We analyzed a total of 225 patients from Guangxi, China with P. falciparum malaria acquired in Africa between 2016 and 2018. All patients were cured completely after treatment. The F446I mutation of the Pfkelch13 gene was detected for the first time from samples of West African P. falciparum, with a frequency of 1.0%. Five haplotypes of Pfcrt that encode residues 72–76 were found, with the wild-type CVMNK sequence predominating (80.8% of samples), suggesting that the parasites might be chloroquine sensitive. For Pfmdr1, N86Y (13.1%) and Y184F (58.8%) were the most prevalent, suggesting that artemether-lumefantrine may not, in general, be a suitable treatment for the group.Conclusions: For the first time, this study detected the F446I mutation of the Pfkelch13 gene from Africa parasites that lacked clinical evidence of resistance. This study provides the latest data for molecular marker surveillance related to antimalarial drug resistance genes Pfkelch13, Pfcrt, and Pfmdr1 imported from Africa, in Guangxi, China from Chinese migrate workers.Clinical Trial Registration: ChiCTROPC17013106.

Low Gut Ruminococcaceae Levels are Associated with Occurrence of Antibiotic-associated Diarrhea

Patients receiving antibiotics often suffer from antibiotic-associated diarrhea (AAD). AAD is of clinical significance as it can result in premature antibiotic discontinuation and suboptimal treatment of infection. The drivers of AAD however, remain poorly understood. We sought to understand if differences in the gut microbiome, both at baseline and during antibiotic administration, would influence the development of AAD. We administered a 3-day course of oral amoxicillin-clavulanate to 30 healthy adult volunteers, and performed a detailed interrogation of their stool microbiome at baseline and up to 4-weeks post antibiotic administration, using 16S rRNA gene sequencing. Lower levels of Ruminococcaceae were significantly and consistently observed from baseline till Day 7 in participants who developed AAD. The probability of AAD could be predicted based on qPCR-derived levels of Faecalibacterium prausnitzii, the most dominant species within the Ruminococcaceae family. Overall, participants who developed AAD experienced a greater decrease in microbial diversity during antibiotic dosing. Our findings suggest that a lack of gut Ruminococcaceae at baseline influences development of AAD. In addition, quantification of F. prausnitzii in stool prior to antibiotic administration may help identify patients at risk of AAD, and aid clinicians in devising individualised treatment regimens to minimise such adverse effects.

Activity of imipenem-relebactam against multi-drug and extensively-drug resistant Burkholderia cepacia complex and Burkholderia gladioli

The Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are opportunistic pathogens that most commonly infect persons with cystic fibrosis or compromised immune systems. Members of the Burkholderia genus are intrinsically multidrug resistant (MDR), possessing both a PenA carbapenemase and an AmpC β-lactamase, which renders treatment of infection due to these species problematic. Here, we tested the β-lactam-β-lactamase inhibitor combination, imipenem-relebactam, against a panel of MDR Bcc and B. gladioli . The addition of relebactam to imipenem dramatically lowered the MICs for Bcc and B . gladioli with only 16% of isolates testing susceptible to imipenem vs. 71.3% being susceptible to the imipenem-relebactam combination. While ceftazidime-avibactam remained the most potent combination drug against this panel of Bcc and B. gladioli , imipenem-relebactam was active against 71.4% of the ceftazidime-avibactam-resistant isolates. Relebactam demonstrated potent inactivation of the Burkholderia multivorans PenA1 with a K i app value of 3.2 μM. Timed mass spectrometry revealed that PenA1 formed a very stable adduct with relebactam, without any detectable desulfation up to 24 hours. Based on our results, imipenem-relebactam may represent an alternative salvage therapy for Bcc and B . gladioli infection, especially in cases where the isolates are resistant to ceftazidime-avibactam.

Coronavirus infection and gut microbiota

At present time, a number of questions regarding the pathophysiological characteristics and therapeutic approaches to the treatment of the new coronavirus infection COVID-19 remain unresolved. In some cases, patients with COVID-19 may experience symptoms of gastrointestinal tract disorder. According to the literature, the new SARS-CoV-2 coronavirus can replicate in the gastrointestinal tract and may affect the gut microbiota. The article aims to review studies about the possible relationship between the gut microbiota condition and the course of COVID-19 infection, as well as to consider the gut microbiota as a potential therapeutic target and probiotic drugs as possible therapeutic agents in the treatment of viral infections, including COVID-19 infection. It is known that gut microbiota condition is one of the factors determining the susceptibility and features of the bodys response to various infectious agents, possibly including the COVID-19 infection. Currently published studies demonstrate a possible relationship between the gut microbiota condition and the course of COVID-19 infection, however, to confirm this hypothesis, additional studies are required, which will allow to make more unambiguous conclusions with subsequent development of new approaches to the prevention and treatment of infection. Potentially a lot of hope in this direction is inspired by the results of probiotics studies, which showed that their use may reduce the frequency and severity of viral infections of the upper respiratory tract. However, currently, there is insufficient data to extrapolate the results of these studies to COVID-19 patients.

USE OF DIALKYL CARBAMOYL CHLORIDE IN THE PREVENTION AND TREATMENT OF BIOFILM IN WOUNDS

Objectives: The aim was to identify the benefits of using Dialkyl Carbamoyl Chloride for the treatment of biofilms in wounds. Methods: This is an integrative literature review that aimed to answer the guiding question: “What are the benefits of using Dialkyl Carbamoyl Chloride in the healing of skin lesions?”. The article selection stages resulted in 13 articles included. Results: The selected articles were grouped into two groups, namely: prevention and treatment of infection in wounds and prevention of surgical site infection, with nine productions in the first group and four in the second. Studies have shown that Dialkyl Carbamoyl Chloride attenuates colonization symptoms, such as odor, pain complaints and oozing, in addition to aiding in the prophylactic management of wound biofilm. Evidence indicates that dressings with Dialkyl Carbamoyl Chloride have no adverse effects, making them viable and safe options for chronic, acute and, mainly, infected injuries. Conclusion: It was identified that Dialkyl Carbamoyl Chloride was able to promote beneficial actions in the treatment of wounds, especially those of greater complexity. The proper choice of dressings and coverings can contribute to the rational use of existing technologies and antimicrobials, culminating in cost reduction and promotion of quality of life for individuals with chronic wounds.

Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control

Burns and other skin injuries are growing concerns as well as challenges in an era of antimicrobial resistance. Novel treatment options to improve the prevention and eradication of infectious skin biofilm-producing pathogens, while enhancing wound healing, are urgently needed for the timely treatment of infection-prone injuries. Treatment of acute skin injuries requires tailoring of formulation to assure both proper skin retention and the appropriate release of incorporated antimicrobials. The challenge remains to formulate antimicrobials with low water solubility, which often requires carriers as the primary vehicle, followed by a secondary skin-friendly vehicle. We focused on widely used chlorhexidine formulated in the chitosan-infused nanocarriers, chitosomes, incorporated into chitosan hydrogel for improved treatment of skin injuries. To prove our hypothesis, lipid nanocarriers and chitosan-comprising nanocarriers (≈250 nm) with membrane-active antimicrobial chlorhexidine were optimized and incorporated into chitosan hydrogel. The biological and antibacterial effects of both vesicles and a vesicles-in-hydrogel system were evaluated. The chitosomes-in-chitosan hydrogel formulation demonstrated promising physical properties and were proven safe. Additionally, the chitosan-based systems, both chitosomes and chitosan hydrogel, showed an improved antimicrobial effect against S. aureus and S. epidermidis compared to the formulations without chitosan. The novel formulation could serve as a foundation for infection prevention and bacterial eradication in acute wounds.