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Veterinary Research Sep 2023Pasteurella multocida is a gram-negative bacterium that causes serious diseases in a wide range of animal species. Inflammasomes are intracellular multimolecular protein...
Pasteurella multocida is a gram-negative bacterium that causes serious diseases in a wide range of animal species. Inflammasomes are intracellular multimolecular protein complexes that play a critical role in host defence against microbial infection. Our previous study showed that bovine P. multocida type A (PmCQ2) infection induces NLRP3 inflammasome activation. However, the exact mechanism underlying PmCQ2-induced NLRP3 inflammasome activation is not clear. Here, we show that NLRP3 inflammasome activation is positively regulated by a scaffold protein called receptor for activated C kinase 1 (RACK1). This study shows that RACK1 expression was downregulated by PmCQ2 infection in primary mouse peritoneal macrophages and mouse tissues, and overexpression of RACK1 prevented PmCQ2-induced cell death and reduced the numbers of adherent and invasive PmCQ2, indicating a modulatory role of RACK1 in the cell death that is induced by P. multocida infection. Next, RACK1 knockdown by siRNA significantly attenuated PmCQ2-induced NLRP3 inflammasome activation, which was accompanied by a reduction in the protein expression of interleukin (IL)-1β, pro-IL-1β, caspase-1 and NLRP3 as well as the formation of ASC specks, while RACK1 overexpression by pcDNA3.1-RACK1 plasmid transfection significantly promoted PmCQ2-induced NLRP3 inflammasome activation; these results showed that RACK1 is essential for NLRP3 inflammasome activation. Furthermore, RACK1 knockdown decreased PmCQ2-induced NF-κB activation, but RACK1 overexpression had the opposite effect. In addition, the immunofluorescence staining and immunoprecipitation results showed that RACK1 colocalized with NLRP3 and that NEK7 and interacted with these proteins. However, inhibition of potassium efflux significantly attenuated the RACK1-NLRP3-NEK7 interaction. Our study demonstrated that RACK1 plays an important role in promoting NLRP3 inflammasome activation by regulating NF-κB and promoting NLRP3 inflammasome assembly.
Topics: Animals; Cattle; Mice; Pasteurella multocida; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; NF-kappa B; Pasteurella Infections; Receptors for Activated C Kinase; Cattle Diseases
PubMed: 37684678
DOI: 10.1186/s13567-023-01195-5 -
Cureus Nov 2023Intra-abdominal complications such as peritoneal abscesses pose significant medical challenges. Over recent years, there has been a heightened focus on refining... (Review)
Review
Intra-abdominal complications such as peritoneal abscesses pose significant medical challenges. Over recent years, there has been a heightened focus on refining treatments for these conditions, such as optimal surgical techniques, drug therapies, and intervention methods. This paper aims to present a comprehensive overview of 10 research studies spanning various countries to highlight recent advancements and findings in the treatment and management of peritoneal abscesses. The paper reviewed 10 trials involving a total of 942 participants, covering diverse methodologies including randomized controlled trials, retrospective analyses, and phase 3 clinical trials. The research spanned countries such as the USA, Finland, Japan, Turkey, India, and China. Key findings included the notable benefits of laparoscopic interventions in appendiceal abscess treatments, which led to quicker recoveries and reduced readmissions compared to conservative approaches. Additionally, certain drug combinations, such as tazobactam/ceftolozane with metronidazole, showcased high clinical efficacy, particularly against resistant bacterial strains. Challenges persist in the early detection of intra-abdominal infections, emphasizing the pivotal role of antimicrobial treatments. Unique therapeutic approaches, like the use of strong acid-electrolyzed water (SAEW) in pediatric appendicitis cases, have proven effective in reducing surgical site infections. Intrabdominal complications such as peritoneal abscesses pose a real challenge. Early detection plays a critical role, which relies on using imaging techniques such as CT scans. Poorly managed mild intra-abdominal diseases can lead to the development of abscesses. Therefore, the implication of highly effective antibiotic combinations such as tazobactam/ceftolozane and metronidazole/ceftriaxone from the start can effectively combat challenging bacterial infections such as Gram-negative and anaerobic bacteria. Surgical procedures remain the most effective method to treat abscesses, and they are usually used as the last resort when drainage, laparoscopy, and other methods fail.
PubMed: 38084178
DOI: 10.7759/cureus.48601 -
Antibiotics (Basel, Switzerland) Jun 2024is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United... (Review)
Review
is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United States of America. The present study aimed to identify all the published cases of in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus databases search. In total, 16 studies provided data on 19 patients with infections by . The median age of the patients was 55 years, and 47.4% were male. The most common infections were those of the bloodstream, the respiratory tract, and the peritoneal cavity. Antimicrobial resistance to cephalosporins, aminoglycosides, and the combination of trimethoprim with sulfamethoxazole was minimal, and these were the most commonly used antimicrobials for treating these infections. No included study provided information on the genetic or molecular mechanism of this pathogen's antimicrobial resistance. The overall mortality was minimal, with only one patient with bacteremia succumbing to the infection. Further studies are needed to better understand this microorganism, its pathogenic potential in humans, and the genetic and molecular mechanisms underlying its antimicrobial resistance, for which very little evidence exists to date.
PubMed: 38927225
DOI: 10.3390/antibiotics13060559 -
Veterinary Medicine and Science Nov 2023To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or...
OBJECTIVE
To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection.
MATERIALS AND METHODS
A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor-3 (TFF-3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I-FABP), myeloperoxidase-anti-neutrophilic cytoplasmic antibody (MPO-ANCA) and proteinase 3-ANCA (PR3-ANCA) concentrations were measured both in serum and effusion samples.
RESULTS
Rectal temperature and respiratory rate were highest in the TE group (p < 0.000). Effusion white blood cell count was higher in the AE group than TE group (p < 0.042). Serum TFF-3, IAP and I-FABP concentrations were higher in cats with effusive FIP than the cats with FECV (p < 0.05). Compared with the AE group, TE group had lower effusion MPO-ANCA (p < 0.036), higher IAP (p < 0.050) and higher TFF-3 (p < 0.016) concentrations.
CLINICAL SIGNIFICANCE
Markers of intestinal and epithelial surface injury were higher in cats with effusive FIP than those with FECV. Compared to cats with abdominal effusions, markers of apoptosis inhibition and immunostimulation to the injured epithelium were more potent in cats with thoracic effusion, suggesting the possibility of a poorer prognosis or more advanced disease in these patients.
Topics: Cats; Animals; Coronavirus, Feline; Feline Infectious Peritonitis; Antibodies, Antineutrophil Cytoplasmic; Coronavirus Infections; Biomarkers; Cat Diseases
PubMed: 37872840
DOI: 10.1002/vms3.1299 -
Nefrologia 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality.... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.
Topics: Humans; Prospective Studies; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Vaccination; Antibodies, Monoclonal; Renal Insufficiency, Chronic
PubMed: 37150670
DOI: 10.1016/j.nefroe.2023.04.005 -
Mediators of Inflammation 2023Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host...
Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host bloodstream. During sepsis, activation of toll-like receptors (TLRs) on immune cells triggers the release of pro-inflammatory cytokines and overstimulates the production of vasodilatory mediators such as nitric oxide (NO). These vascular changes lead to widespread inflammation, tissue damage, multiple organ failure, and often death. New therapeutic options are urgently needed. To this end, thiostrepton (TST) has emerged as a candidate for sepsis treatment due to its action as an antibiotic and anti-inflammatory molecule (TLR7-9 inhibitor). Reports in the literature suggest that TLR9 inhibition substantially suppresses the excessive host inflammatory response and attenuates sepsis-induced mortality in the cecal ligation and puncture (CLP) murine model of sepsis. However, to the best of our knowledge, TST has never been directly tested as a therapeutic option for the management of sepsis, possibly due to its low water solubility and drug delivery issues. These facts prompted us to test the central hypothesis that TST encapsulated in phospholipid sterically stabilized micelles (TST-SSM) could be developed into a novel treatment for sepsis. Thus, using our published method of encapsulating the hydrophobic antibiotic TST-SSM, we evaluated the efficacy of TST-SSM nanomedicine in the murine model of polymicrobial sepsis. We found that TST-SSM increased the median survival of CLP-induced septic mice from 31 to 44 hr by reducing the bacterial burden in the blood and peritoneal lavage. Moreover, plasma levels of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor-alpha) and NO derivatives were also reduced, whereas renal and hepatic function biomarkers creatinine and aspartate transferase were significantly improved. In conclusion, we identified that TST-SSM nanomedicine has significant potential as a therapeutic agent for sepsis management, primarily due to its anti-inflammatory and antibiotic properties.
Topics: Animals; Mice; Thiostrepton; Toll-Like Receptor 9; Disease Models, Animal; Nanomedicine; Sepsis; Inflammation; Anti-Bacterial Agents; Cytokines
PubMed: 37662481
DOI: 10.1155/2023/4035516 -
Molecular Medicine (Cambridge, Mass.) Nov 2023Maresin1 (MaR1) is a potent lipid mediator that exhibits significant anti-inflammatory activity in the context of several inflammatory diseases. A previous study...
BACKGROUND
Maresin1 (MaR1) is a potent lipid mediator that exhibits significant anti-inflammatory activity in the context of several inflammatory diseases. A previous study reported that MaR1 could suppress MSU crystal-induced peritonitis in mice. To date, the molecular mechanism by which MaR1 inhibits MSU crystal-induced inflammation remains poorly understood.
METHODS
Mousebone marrow-derived macrophages (BMDMs) were pretreated with MaR1 and then stimulated with FAs (palmitic, C16:0 and stearic, C18:0) plus MSU crystals (FAs + MSUc). In vivo, the effects of MaR1 treatment or Prdx5 deficiency on MSUc induced peritonitis and arthritis mouse models were evaluated.
RESULTS
The current study indicated that MaR1 effectively suppressed MSUc induced inflammation in vitro and in vivo. MaR1 reversed the decrease in Prdx5 mRNA and protein levels induced by FAs + MSUc. Further assays demonstrated that MaR1 acceleratedPrdx5 expression by regulating the Keap1-Nrf2 signaling axis. Activation of AMPK by Prdx5 improved homeostasis of the TXNIP and TRX proteins and alleviated mitochondrial fragmentation. In addition, Prdx5 overexpression inhibited the expression of CPT1A, a key enzyme for fatty acid oxidation (FAO). Prdx5 protected against defects in FA + MSUc induced FAO and the urea cycle.
CONCLUSION
MaR1 treatment effectively attenuated MSUc induced inflammation by upregulating Prdx5 expression. Our study provides a new strategy by which Prdx5 may help prevent acute gout attacks.
Topics: Mice; Animals; Kelch-Like ECH-Associated Protein 1; Uric Acid; NF-E2-Related Factor 2; Inflammation; Peritonitis
PubMed: 37996809
DOI: 10.1186/s10020-023-00756-w -
Renal abscess complicating acute pyelonephritis in children: Two cases report and literature review.Medicine Dec 2023To describe the diagnostic and treatment approaches of renal abscesses complicated with acute pyelonephritis in children. (Review)
Review
RATIONALE
To describe the diagnostic and treatment approaches of renal abscesses complicated with acute pyelonephritis in children.
PATIENT CONCERNS
Two children presented with fever, vomiting, and abdominal pain with no typical manifestations, like frequent urination, urgency, dysuria, hematuria, foam urine, and lumbago. Renal abscess complicating acute pyelonephritis was diagnosed by B-ultrasound and computed tomography enhancement. Moreover, inflammatory markers were elevated significantly, but routine blood and urine cultures were repeatedly negative. The empirical anti-infection therapy had no obvious effect. A pathogenic diagnosis was confirmed in case two, and macro gene detection in blood and urine guided the follow-up treatment.
DIAGNOSES
Both children were diagnosed with acute gastroenteritis on admission, but renal abscess complicating acute pyelonephritis were diagnosed by imaging examination.
INTERVENTIONS
Both children were given anti-infection therapy of third-generation cephalosporin, which had no obvious effect. Routine blood and urine cultures were repeatedly negative. Case one was changed to piperacillin sodium tazobactam. We further carried out blood and urinary metagenomic next-generation sequencing detection for case two. Meanwhile, meropenem and linezolid anti-infection treatment was given. The results showed overlapping infection with Escherichia coli and Enterococcus faecalis. According to the genetic test results, amoxicillin clavulanate potassium combined with nitrofurantoin were prescribed after discharge.
OUTCOMES
Clinical symptoms of the 2 children disappeared, the infection was controlled, and imaging showed that renal abscess complicated with acute pyelonephritis disappeared.
LESSONS
The clinical spectrum of renal abscess complicating acute pyelonephritis is vague, with no specific manifestations, and can be easily misdiagnosed. B-ultrasound and computed tomography enhancement are helpful in making a definite diagnosis. Moreover, the sensitivity of routine culture is low, and metagenomic next-generation sequencing might be helpful to detect pathogenic microorganisms and guided treatment. Early treatment with broad-spectrum antibiotics might have favorable outcomes.
Topics: Child; Humans; Abscess; Pyelonephritis; Urinary Tract Infections; Kidney Diseases; Anti-Bacterial Agents; Escherichia coli; Tomography, X-Ray Computed; Peritoneal Diseases
PubMed: 38050281
DOI: 10.1097/MD.0000000000036355 -
Healthcare (Basel, Switzerland) Mar 2024mHealth has been utilized in the care of patients with chronic kidney disease, allowing the collection of patient health-related data, offering disease-related... (Review)
Review
mHealth has been utilized in the care of patients with chronic kidney disease, allowing the collection of patient health-related data, offering disease-related information, enabling the tracking and recording of biochemical parameters, and enabling communication with healthcare providers in real time through applications. mHealth may improve the health outcomes in patients with peritoneal dialysis. This systematic review aimed to summarize evidence regarding the functionality and usability of mHealth apps in patients with peritoneal dialysis. We conducted a comprehensive literature review, searching in five databases, including CINAHL, Cochrane, PsycINFO, PubMed, and Web of Science, to retrieve titles and abstracts related to peritoneal dialysis and mHealth applications for PRISMA recommendations from January 2013 to December 2023. Overall, 11 studies met all the inclusion criteria. The functionality of mHealth apps included inform, instruct, record, display, guide, remind/alert, and communicate. Most of the apps have multifunctionality. The usability was categorized into three aspects: efficiency (self-efficacy and usability), satisfaction, and effectiveness (underwent kidney transplantation and switched to hemodialysis, rehospitalization, peritonitis rate, infection rates at exit sites, mortality, fluid overload, inadequate solute clearance, biochemical values, quality of life, consumer quality index, and technology readiness). Generally, outcomes in the intervention group had better effects compared to those in the control group. Multifunctional mHealth apps show a good potential in improving the efficiency, satisfaction, and effectiveness for patients compared to traditional care. Future research should include more studies and participants to explore and verify the long-term effectiveness of mHealth apps.
PubMed: 38470704
DOI: 10.3390/healthcare12050593 -
Rhode Island Medical Journal (2013) Feb 2024Peritonitis, a serious complication of peritoneal dialysis (PD), can be caused by opportunistic pathogens like Micrococcus species on rare occasions. We present a case...
Peritonitis, a serious complication of peritoneal dialysis (PD), can be caused by opportunistic pathogens like Micrococcus species on rare occasions. We present a case of Micrococcus sp peritonitis in a 55-year-old female with end-stage kidney disease on continuous cycling peritoneal dialysis for one year who presented with cloudy effluent. Initial treatment against Micrococcus sp with vancomycin, gentamicin, and prophylactic oral nystatin was successful. However, one month later, the patient presented with abdominal pain and dialysate culture again grew Micrococcus sp. Treatment with vancomycin was unsuccessful in resolving culture positivity. The patient was transitioned to hemodialysis for non-medical reasons and then was later restarted on PD without further peritonitis episodes. Micrococcus sp peritonitis in PD poses treatment challenges due to limited guidelines. Intraperitoneal vancomycin is commonly used to target Micrococcus isolates although there is a high incidence of treatment failure. This case report highlights the need for continued reporting to enhance identification, prevention, and patient outcomes in Micrococcus sp peritonitis during PD.
Topics: Female; Humans; Middle Aged; Vancomycin; Micrococcus; Peritoneal Dialysis; Peritonitis; Kidney Failure, Chronic; Anti-Bacterial Agents
PubMed: 38285745
DOI: No ID Found