Infection Inflammation Research Articles

Galectin-9 mediates gut-associated inflammation and disruption of tight junctions

Abstract Background: High levels of Galectin-9 (Gal-9), a β-galactoside-binding mammalian lectin, are associated with systemic inflammation in chronic viral infections like HIV, despite viral suppression by ART. Gut-systemic microbial translocation is a major contributor of persistent inflammation. Whether Gal-9 influences the integrity of the gut during viral infections remains unknown. Objective: Here we investigated the impact of Gal-9 in the interplay between gut-systemic microbial translocation in the setting of well-treated chronic HIV infection. Method: We assessed the levels of Gal-9 and sCD14 in the plasma of people with HIV on ART (PWH; n=25) and people without HIV (PWOH; n=15) by ELISA. The integrity of the gut epithelium in the presence and absence of rGal-9 was assessed in the HT-29 cell line by immunofluorescence. TNFa was used as a positive control to disrupt gut integrity. The levels of TNFa were measured by qPCR. Non parametric tests were used in the analysis. Results: Plasma Gal-9 and sCD14 were elevated in PWH compared to PWOH (all p<0.0001). Further, high Gal-9 levels correlated with high sCD14 in both the PWH (r=0.43, p=0.0317) and PWOH (r=0.79, p=0.0006) groups. Immunofluorescence revealed disruption of the Claudin tight junctions in vitroafter 24 hrs of rGal-9 treatment. rGal-9 also induced a 6-fold increase in the expression of TNFα in HT-29 cells. Conclusion: Our results show that Gal-9 is associated with markers of gut-systemic microbial translocation irrespective of HIV status and given the direct effects of rGal-9 on tight junction barrier function, targeting Gal-9 either by exploiting its secretory pathways or competitive blockade may serve as a novel therapeutic approach to control gut-associated inflammation.

Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2

The creation of safe and effective vaccines that induce potent cellular and humoral immune responses against SARS-CoV-2 is urgently needed to end the global COVID-19 epidemic. Here, we developed an alphavirus-derived self-replicating RNA (repRNA)-based vaccine platform encoding the receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein. The repRNA triggers prolonged antigen expression compared with conventional mRNA due to the replication machinery of repRNA. To improve the delivery and vaccine efficacy of repRNA, we developed a self-assembling liposome-protamine-RNA (LPR) nanoparticle with highly efficient encapsulation and transfection of repRNA. LPR-repRNA vaccines substantially activated type I interferon response and innate immune signaling pathways. Subcutaneous immunization of LPR-repRNA-RBD led to prolonged antigen expression, stimulation of innate immune cells, and induction of germinal center response in draining lymph nodes. LPR-repRNA-RBD induced antigen-specific Tcell responses and skewed cellular immunity toward an effector memory CD8+ Tcell response. Immunizations with LPR-repRNA-RBD triggered the production of anti-RBD IgG antibodies and induced neutralizing antibody response against SARS-CoV-2 pseudovirus. LPR-repRNA-RBD vaccines reduced SARS-CoV-2 infection and lung inflammation in mice. Altogether, these data suggest that the LPR-repRNA platform can be a promising avenue for COVID-19 vaccine development.

Hepcidin expression in the trigeminal ganglion and the oral mucosa in an oral ulcerative mucositis rat model.

Severe intraoral pain induces difficulty in eating and speaking, leading to a decline in the quality of life. However, the molecular mechanisms underlying intraoral pain remain unclear. Here, we investigated gene modulation in the trigeminal ganglion and intraoral pain-related behavior in a rat model of acetic acid-induced oral ulcerative mucositis. Oral ulceration was observed on day 2 after acetic acid treatment to the oral mucosa of male Wistar rats, causing spontaneous pain and mechanical allodynia. Deoxyribonucleic acid microarray analysis of trigeminal ganglion tissue indicated that Hamp (a hepcidin gene that regulates cellular iron transport) was the most upregulated gene. In the oral ulcerative mucositis model, the upregulation of Hamp was also induced in the ulcer region but not in the liver, with no increase in hepcidin levels in the plasma and saliva, indicating that hepcidin was produced locally in the ulcer region in the model. Systemic antibiotic pretreatment did not increase the mRNA levels of Hamp in the trigeminal ganglion and ulcer regions. Hepcidin injection into the oral mucosa enhanced neuronal excitability in response to noxious mechanical stimulation of the oral mucosa in trigeminal spinal subnucleus interpolaris/caudalis neurons. These results imply that oral ulcerative mucositis induces oral mucosal pain because of infectious inflammation of the ulcerative area and potentiates Hamp, which represents anti-bacterial and anti-peptidase gene expression in the ulcer region and trigeminal ganglion. The regulation of cellular iron transport by hepcidin is likely involved in oral ulcerative mucositis-induced pain.

The role of group 3 innate lymphoid cellin intestinal disease.

Group 3 innate lymphoid cells (ILC3s), a novel subpopulation of lymphocytes enriched in the intestinal mucosa, are currently considered as key sentinels in maintaining intestinal immune homeostasis. ILC3s can secrete a series of cytokines such as IL-22 to eliminate intestinal luminal antigens, promote epithelial tissue repair and mucosal barrier integrity, and regulate intestinal immunity by integrating multiple signals from the environment and the host. However, ILC3 dysfunction may be associated with the development and progression of various diseases in the gut. Therefore, in this review, we will discuss the role of ILC3 in intestinal diseases such as enteric infectious diseases, intestinal inflammation, and tumors, with a focus on recent research advances and discoveries to explore potential therapeutic targets.

Insights into the Microbicidal, Antibiofilm, Antioxidant and Toxicity Profile of New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives.

The unprecedented increase in microbial resistance rates to all current drugs raises an acute need for the design of more effective antimicrobial strategies. Moreover, the importance of oxidative stress due to chronic inflammation in infections with resistant bacteria represents a key factor for the development of new antibacterial agents with potential antioxidant effects. Thus, the purpose of this study was to bioevaluate new O-aryl-carbamoyl-oxymino-fluorene derivatives for their potential use against infectious diseases. With this aim, their antimicrobial effect was evaluated using quantitative assays (minimum inhibitory/bactericidal/biofilms inhibitory concentrations) (MIC/MBC/MBIC), the obtained values being 0.156-10/0.312-10/0.009-1.25 mg/mL), while some of the involved mechanisms (i.e., membrane depolarization) were investigated by flow cytometry. The antioxidant activity was evaluated by studying the scavenger capacity of DPPH and ABTS•+ radicals and the toxicity was tested in vitro on three cell lines and in vivo on the crustacean Artemia franciscana Kellog. The four compounds derived from 9H-fluoren-9-one oxime proved to exhibit promising antimicrobial features and particularly, a significant antibiofilm activity. The presence of chlorine induced an electron-withdrawing effect, favoring the anti-Staphylococcus aureus and that of the methyl group exhibited a +I effect of enhancing the anti-Candida albicans activity. The IC50 values calculated in the two toxicity assays revealed similar values and the potential of these compounds to inhibit the proliferation of tumoral cells. Taken together, all these data demonstrate the potential of the tested compounds to be further used for the development of novel antimicrobial and anticancer agents.

2023 TERMIS – AMERICAS Conference & Exhibition Boston Marriott Copley Place April 11–14, 2023

2023 TERMIS – AMERICAS Conference & Exhibition Boston Marriott Copley Place April 11–14, 2023

Relationship of maternal inflammatory response and fetal inflammatory response to duration and intensity of intra-amniotic infection and inflammation

IntroductionWe aimed to use two indices, amniotic fluid interleukin-6 (IL-6) concentration at diagnosis and diagnosis-to-delivery interval, to clarify the frequencies of maternal inflammatory response (MIR) and fetal inflammatory response (FIR) in the placenta of patients with intra-amniotic infection and intra-amniotic inflammation (IAI). MethodsThis is a single-center retrospective cohort study. From August 2014 to April 2020, participants were diagnosed with IAI with or without microbial invasion of the amniotic cavity (MIAC) using amniocentesis. IAI was defined as concentrations of amniotic IL-6 ≥ 2.6 ng/mL. MIAC was defined as a positive amniotic fluid culture. IAI with MIAC was defined as an intra-amniotic infection. We calculated the cut-off values for IL-6 concentration in the amniotic fluid at diagnosis and the diagnosis-to-delivery interval for MIR-positive cases among those with intra-amniotic infection. ResultsThe amniotic fluid IL-6 concentration at diagnosis and diagnosis-to-delivery interval were 15.8 ng/mL and 12 h, respectively. Among cases with intra-amniotic infection, MIR was 98% (52/53) positive, i.e., when either of the two cut-off values was exceeded. There were no significant differences between the frequencies of MIR and FIR. In cases with IAI but no MIAC, the frequencies of MIR and FIR were significantly lower than those with intra-amniotic infection, except when neither of the two cut-off values was exceeded. DiscussionWe clarified the MIR- and FIR-positive cases in intra-amniotic infection and cases with IAI but no MIAC according to condition, including the diagnosis-to-delivery interval.

Combined use of CRP with neutrophil-to-lymphocyte ratio in differentiating between infectious and noninfectious inflammation in hemodialysis patients

We tested whether CRP combined with the neutrophil-to-lymphocyte ratio (NLR) optimizes the prediction of infectious inflammation in hemodialysis patients. We conducted a retrospective study of 774 (mean age 71.1 ± 12.8 years, 35% women) hemodialysis patients from our institution, hospitalized between 2007 and 2021 for various reasons, with CRP levels available at admission. Infection was defined according to the International Sepsis Definition Conference criteria. An algorithm for the optimal CRP and NLR cutoff points for predicting infection was developed based on a decision tree analysis in the training cohort (n = 620) and then tested in the validation cohort (n = 154). A CRP level above 40 mg/L (obtained as the cutoff point in predicting infections in the training group, using ROC curve analysis) predicted an infection diagnosis with a sensitivity of 75% and a specificity of 76% with an odds ratio (OR) of 9.37 (95% CI: 5.36–16.39), according to a multivariate logistic regression analysis. Whereas, CRP levels above 23 mg/L together with an NLR above 9.7 predicted an infection diagnosis with a sensitivity of 69% and a specificity of 84% with an OR of 25.59 (95% CI: 9.73–67.31). All these results were reproduced in the validation set. Combined use of CRP with NLR may lower the CRP cutoff point in distinguishing between infectious and noninfectious inflammation in hemodialysis patients.

Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

Cyproheptadine Treatment of COVID-19-Induced Enteritis: Implications for Hyperinflammatory Phase Management

ABSTRACT A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.

Is Imaging Bacteria with PET a Realistic Option or an Illusion?

The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome.

The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70-80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, "Why this variation?" remains largely unanswered.

Phytochemicals Identification and Bioactive Compounds Estimation of Artemisia Species Grown in Saudia Arabia

Artemisia species are very important medicinal plants, particularly in the Middle East and in developing countries. Their products have been used in traditional and medicine contemporary for the treating of infectious ulcers, gangrenous ulcers, inflammations, and malaria. Artemisinin derived from Artemisia species has been used as a drug in many countries for malaria disease treatment. Hence, this study aimed to identify and evaluate the bioactive compounds of three species of Artemisia (Artemisia judaica, Artemisia monosperma, and Artemisia sieberi) growing in Saudi Arabia. Therefore, several analytical techniques, such as gas chromatography-mass spectrometry (GC-MS), UV-Visible spectrophotometry (UV-Vis), and high-performance liquid chromatography (HPLC), with reference standards, were used. The GC-MS analysis of the artemisia species revealed many bioactive constituents associated with plant secondary metabolites; some of these identified phytochemical components have biological activity. A. Judaica showed the highest number of bioactive compounds, followed by A. sieberi and A. monosperma. Further, the total phenol, total flavonoid, total tannin, terpenoids, and TCA were estimated. Furthermore, biomolecules such gallic acid, tannin acid, quercetin, and artemisinin in different artemisia species were quantified using HPLC with the reference standard. The amount of artemisinin in the leaf extract of these species (A. sieberi, A. Judaica, and A. monosperma) was found to be about 3.01, 2.5, and 1.9 mg/g DW, respectively. Moreover, the antioxidant activity of the samples was estimated. The obtained results have shown that these species possessed high antioxidant activity, and the scavenging of the DPPH radical and hydrogen peroxide were found to be raised with the increase in the plant extract concentration. This reflects the number of bioactive compounds in these species. The findings of this research support and justify the utilization of Artemisia species in folk medicine in the Middle East.

Local therapy of acute otitis media in children

Acute otitis media (AOM), one of the most common infectious and inflammatory diseases in infants, toddlers and young children, is defined as an infectious inflammation of the middle ear, usually bacterial, often with earache, fever, and possibly otorrhea. Almost all children suffer from otitis media, 80–90% – at preschool age. The frequency of acute otitis media in children in a megapolis is more than 4 000 cases per 100 000 population, however, given the large proportion of asymptomatic variants against the background of acute respiratory infections, insufficient equipment of pediatricians with otoscopes, registration of acute otitis media almost exclusively by ENT doctors, the frequency of acute otitis media may be significantly higher. The clinical picture may be nonspecific. Ear pain and otoscopy are decisive for the diagnosis. The severity of inflammation correlates well with the scale of visual assessment of pain according to the child’s facial expressions. The aims of treatment are to relieve pain using topical or systemic analgesics, decide together with an ENT specialist on the need for antibiotic therapy, avoid not indicated antibiotic therapy, prevent complications (tympanic membrane perforation, acute mastoiditis, meningitis). With unexpressed otitis media, it is advisable to use symptomatic therapy and drops. A complex of compounds (lidocaine, phenazone) provides a quick therapeutic effect. Topical anaesthetics block the transmission of the pain signal from the receptor to the central nervous system through the inhibition of voltage-gated sodium channels. The symptomatic treatment (analgesics, antipyretics, topical therapy) results in improvement in 60% of patients within the next 24 hours, and in 80% within the next 3 days.For prophylaxis of otitis, it is necessary to prevent acute respiratory infections, do vaccination against influenza and pneumococcal infections, avoid exposure to tobacco smoke, and keep babies breastfeeding.

Macrophage-Specific Coxsackievirus and Adenovirus Receptor Deletion Enhances Macrophage M1 Polarity in CVB3-Induced Myocarditis

The coxsackievirus and adenovirus receptor (CAR) is very well known as an epithelial tight junction and cardiac intercalated disc protein; it mediates attachment and infection via the coxsackievirus B3 (CVB3) and type 5 adenovirus. Macrophages play important roles in early immunity during viral infections. However, the role of CAR in macrophages is not well studied in relation to CVB3 infection. In this study, the function of CAR was observed in the Raw264.7 mouse macrophage cell line. CAR expression was stimulated by treatment with lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α). In thioglycollate-induced peritonitis, the peritoneal macrophage was activated and CAR expression was increased. The macrophage-specific CAR conditional knockout mice (KO) were generated from lysozyme Cre mice. The expression of inflammatory cytokine (IL-1β and TNF-α) was attenuated in the KO mice's peritoneal macrophage after LPS treatment. In addition, the virus was not replicated in CAR-deleted macrophages. The organ virus replication was not significantly different in both wild-type (WT) and KO mice at days three and seven post-infection (p.i). However, the inflammatory M1 polarity genes (IL-1β, IL-6, TNF-α and MCP-1) were significantly increased, with increased rates of myocarditis in the heart of KO mice compared to those of WT mice. In contrast, type1 interferon (IFN-α and β) was significantly decreased in the heart of KO mice. Serum chemokine CXCL-11 was increased in the KO mice at day three p.i. compared to the WT mice. The attenuation of IFN-α and β in macrophage CAR deletion induced higher levels of CXCL-11 and more increased CD4 and CD8 T cells in KO mice hearts compared to those of WT mice at day seven p.i. These results demonstrate that macrophage-specific CAR deletion increased the macrophage M1 polarity and myocarditis in CVB3 infection. In addition, chemokine CXCL-11 expression was increased, and stimulated CD4 and CD8 T cell activity. Macrophage CAR may be important for the regulation of innate-immunity-induced local inflammation in CVB3 infection.

COVID-19 and Frailty.

Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older age is also associated with decreased kidney function and is consequently associated with an increased risk of cardiovascular disease. All of this in the course of COVID-19 infection can worsen and promote the progression of chronic kidney damage and all its sequelae. Frailty is a condition characterized by the decline in function of several homeostatic systems, leading to increased vulnerability to stressors and risk of adverse health outcomes. Thus, it is very likely that frailty, together with comorbidities, may have contributed to the high vulnerability to severe clinical manifestations and deaths from COVID-19 among older people. The combination of viral infection and chronic inflammation in the elderly could cause multiple unforeseen harmful consequences, affecting overall disability and mortality rates. In post-COVID-19 patients, inflammation has been implicated in sarcopenia progression, functional activity decline, and dementia. After the pandemic, it is imperative to shine a spotlight on these sequelae so that we can be prepared for the future outcomes of the ongoing pandemic. Here, we discuss the potential long-term consequences of SARS-CoV-2 infection and its possibility of causing permanent damage to the precarious balance existing in the frail elderly with multiple pathologies.

The first Brevinin-1 antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo.

Antimicrobial peptide is one important component of the first protective barrier of organisms. They not only have potent antimicrobial activity which can protect the body from the invading pathogens, but also participate in the immune regulation of the body. In this study, a Brevinin-1 peptide named by Brevinin-1GHd was identified from Hoplobatrachus rugulosus, and the similarity of mature peptide sequence among Brevinin-1GHd, Brevinin-1HL and Brevinin-1GHa supported the close species relationship between H. rugulosus, Hylarana latouchii and Hylarana guertheri. Moreover, the secondary structure of Brevinin-1GHd was found to possess α-helical characteristics and high thermal stability. In addition, Brevinin-1GHd could bind to LPS with a Kd value of 6.49 ± 5.40 mM and suppress the release of TNF-α, NO, IL-6 and IL-1β by inactivation of MAPK signaling pathway in RAW 264.7 cells induced by LPS. Furtherly, Brevinin-1GHd had a significant inhibitory effect on acute edema development in the right paw of mice injected by carrageenan. Thus, the significant LPS-neutralizing and anti-inflammatory activities of Brevinin-1GHd were demonstrated in this study, which made it become the first Brevinin-1 family peptide with anti-inflammatory activity reported so far, and the biological activity of Brevinin-1GHd made it promising to be a novel therapeutic drug for infectious inflammation.

The interplay between hypovitaminosis D and the immune dysfunction in the arteriovenous thrombotic complications of the sever coronavirus disease 2019 (COVID-19) infection.

Thromboembolic complications including cerebrovascular accidents, pulmonary embolism, myocardial infarction, deep vein thrombosis and disseminating intravascular coagulopathy are serious encounters in sever coronavirus disease 2019 (COVID-19) infected patients. This worsens the prognosis and may lead to death or life long morbidities. The laboratory finding of the disturbed haemostasias and the hyperinflammatory response are almost invariably present in COVID-19 patients. Multiple treatment modalities are utilized by the healthcare professionals to overcome the cytokine storm, oxidative stress, endothelial dysfunction, and coagulopathy in these patients. The combined actions of vitamin D (VitD) as a steroid hormone with anti-inflammatory, immunomodulatory, and antithrombotic properties increase the potential of the possible involvement of hypovitaminosis D in the thromboembolic complications of COVID-19 infection, and stimulated researchers and physicians to administer VitD therapy to prevent the infection and/or overcome the disease complications. The current review highlighted the immunomodulatory, anti-inflammatory, antioxidative and hemostatic functions of VitD and its interrelation with the renin-angiotensin-aldosterone system (RAAS) pathway and the complement system. Additionally, the association of VitD deficiency with the incidence and progression of COVID-19 infection and the associated cytokine storm, oxidative stress, hypercoagulability, and endothelial dysfunction were emphasized. Normalizing VitD levels by daily low dose therapy in patients with hypovitaminosis D below (25 nmol/l) is essential for a balanced immune response and maintaining the health of the pulmonary epithelium. It protects against upper respiratory tract infections and decreases the complications of COVID-19 infections. Understanding the role of VitD and its associated molecules in the protection against the coagulopathy, vasculopathy, inflammation, oxidative stress and endothelial dysfunction in COVID-19 infection could lead to new therapeutic strategies to prevent, treat, and limit the complications of this deadly virus infection.

Preclinical evaluation of the effect of periodontal regeneration by carbonate apatite in a canine one-wall intrabony defect model.

This study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, β-tricalcium phosphate (β-TCP), and carbonate apatite (CO3Ap) in dogs. The mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4mm×5mm (mesio-distal width×depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing β-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed. No ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and β-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P<0.05). The bone contact percentage of the residual granules was significantly higher in the CO3Ap group than in the β-TCP group (P<0.05). Although this study has limitations, the findings revealed the safety and efficacy of CO3Ap for periodontal regeneration in one-wall intrabony defects in dogs, and CO3Ap has a better ability to integrate with bone than β-TCP.

Extracorporeal Shock Wave Therapy and a New Assessment Tool for Intractable Wounds of the Limbs

Background: Extracorporeal shock wave therapy (ESWT) is indicated for intractable skin wounds and skin ulcers; however, assessing its efficacy for wounds at the periphery of the extremities may be difficult depending on the wound size (small wounds are challenging to differentiate over time with existing scores) and due to unclear metrics for assessing the amount of exudate and inflammation. To overcome this issue, we developed the Hand and Foot Wound Assessment Tool (HFWAT), comprising area and size, necrotic tissue and healthy granulation tissue, depth, amount of exudate, and inflammation and signs of infection. This study aimed to examine the effect of ESWT on obliterating limb wounds and evaluate outcomes using the HFWAT.Methods: The study included seven patients (four males, three females; 63.4±14.0 years) who visited our hospital between April 2018 and March 2020 and presented with persistent skin wounds on the hands and feet that did not heal despite treatment for more than 2 weeks. Patients received an energy flux density of 0.01 mJ/mm2, which was gradually increased. The HFWAT was used to evaluate the wound, and the pre- and post-ESWT scores were compared.Results: Successful wound healing was observed in all patients following ESWT. The median HFWAT score improved from 9.0 (interquartile range, 9–10) points before ESWT to 0.0 (interquartile range, 0–0) points at the final evaluation (P=0.05, n=7).Conclusion: ESWT was effective for intractable wounds, as demonstrated by the significantly improved HFWAT score. Furthermore, the HFWAT could be valuable for assessing small wounds in the peripheral extremities.